[Senate Hearing 112-]
[From the U.S. Government Publishing Office]



 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2012

                              ----------                              


                        WEDNESDAY, MAY 11, 2011

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:59 a.m., in room SD-124, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Reed, Mikulski, Brown, Shelby, 
Kirk and Moran.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF DR. FRANCIS S. COLLINS, DIRECTOR
ACCOMPANIED BY:
        HAROLD VARMUS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        SUSAN B. SHURIN, M.D., ACTING DIRECTOR, NATIONAL HEART, LUNG, 
            AND BLOOD INSTITUTE
        DR. GRIFFIN RODGERS, DIRECTOR, NATIONAL INSTITUTE OF DIABETES, 
            DIGESTIVE AND KIDNEY DISEASES

                OPENING STATEMENT OF SENATOR TOM HARKIN

    Senator Harkin. The Senate Subcommittee on Labor, Health 
and Human Services, and Education will now come to order.
    First of all, Dr. Collins, welcome back to the 
subcommittee. We welcome also Dr. Harold Varmus, Director of 
the National Cancer Institute; Dr. Tony Fauci, Director of the 
National Institute of Allergy and Infectious Diseases; Dr. 
Griffin Rodgers, Director of the National Institute of 
Diabetes, Digestive and Kidney Diseases; and Dr. Susan Shurin, 
Director of the National Heart, Lung, and Blood Institute.
    This subcommittee holds an appropriations hearing on the 
NIH budget every year, and every year I am both inspired by the 
dedication of the scientists who testify before us and proud 
that their accomplishments have made America the world leader 
in biomedical research. But in recent years, our Nation's 
status in that regard has been threatened. While China and 
Singapore make massive investments in research, here in the 
United States we're pulling back.
    The fiscal year 2011 appropriations bill that Congress 
passed last month cut NIH funding by $322 million below the 
fiscal year 2010 level. When you consider how much funding was 
needed to keep up with inflation, the cut was more like $1.3 
billion, taking inflation into account.
    We should be thankful that the result wasn't significantly 
worse. H.R. 1, the spending bill passed by the House majority, 
would have cut NIH funding by $1.6 billion or $2.6 billion if 
you counted inflation. Fortunately, the Senate rejected that 
plan.
    But even the compromise bill that was ultimately signed in 
law will result in a success rate for NIH research grants, I'm 
told, of just 17 or 18 percent, meaning just one out of every 
six peer-reviewed application will be approved. And, again, I 
am informed that that is the lowest success rate on record for 
NIH.
    What a dismal downturn from what Senator Specter and I, and 
others did back in the late 1900s and early 2000 when we 
doubled the funding of NIH and we got the success rate up, I 
think--if I'm not mistaken. You correct me, Dr. Collins--up in 
the 20-30 percent range, somewhere in there. And we thought we 
were on a path to continue that kind of a success rate. Now, 
it's down lowest on record.
    And there is cause to fear even bigger cuts next year. The 
budget plan approved by the House last month would cut health 
funding by 9 percent in fiscal year 2012. If that plan were 
approved, severe reductions to NIH research would be 
unavoidable.
    That doesn't make sense. Let's set aside for a moment any 
thoughts about the moral value of trying to improve people's 
health, and just look at the issue from a purely economic 
standpoint. NIH research is one of the best investments this 
country can make.
    A study released yesterday by United for Medical Research 
concluded that in fiscal year 2010, NIH funding supported 
almost 500,000 jobs across country. And I always have to remind 
people that only a small percentage of that goes to NIH in 
Bethesda, Maryland. I want Senator Mikulski to know that. Most 
is awarded to researchers at academic institutions all over the 
United States.
    Another study by Battelle examined the specific impact of 
the Human Genome Project, which was overseen, again, by Dr. 
Collins and completed in 2003. The Federal Government spent a 
total of $3.8 billion on this historic initiative. A lot of 
money, but the return on the investment is staggering. 
According to the Battelle study that $3.8 billion translated 
into an economic output of $796 billion between 1988 and 2010. 
And, of course, we'll be seeing benefits from the Human Genome 
Project for many more decades to come. In fact, when I was 
reading all of your testimonies last night, what struck me in 
each one of them there were references made back to genomic 
research in every single case of the institutes who are 
represented here.
    So the lesson is clear. Biomedical research is one of the 
engines that drive our economy. If we want our economy to grow, 
both immediately and in the long term, that engine needs fuel. 
Drastically cutting NIH, as the House budget would force us to 
do, would be a classic case of penny wise and pound foolish 
thinking. That, again, is just on the economic side.
    On the human side, though, the great advances that have 
been made in cancer research and what we have done to lessen 
the threat of cancer--young kids now with leukemia are being 
cured at an almost 100 percent rate. Maybe that's not quite 
right, but pretty darn close, things that were unheard of just 
a few years ago. The advances that we're making in infectious 
diseases, unheard of 20 years ago when I first came on this 
subcommittee. Well, that's been 25 years ago, but great 
advances have been made. Just stark.
    So, from the human standpoint, in helping people have 
better lives and overcoming some of the dreaded diseases that 
have plagued mankind for so long, on both fronts, biomedical 
research is the place to go and we ought not to be penny wise 
and pound foolish on that.
    And so now I'll recognize my ranking member, Senator 
Shelby, for an opening statement.

                 STATEMENT OF SENATOR RICHARD C. SHELBY

    Senator Shelby. Thank you, Mr. Chairman. I appreciate you 
holding this hearing today to discuss the vital mission carried 
out by the National Institutes of Health.
    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.
    I support Federal investment in basic biomedical research 
and development. Research carried out by the NIH and its 
network of 325,000 researchers at 3,000 institutions across the 
country serves the Nation with the goal of improving human 
health. As research becomes more expensive and private capital 
dries up, I believe it's critical to ensure support for 
translational research; that is, research that moves a 
potential therapy from development to the market.
    The NIH has developed an interesting proposal with the 
establishment of the National Center for Advancing 
Translational Sciences, NCATS. NCATS is intended to fill the 
gap between advances in scientific understanding of disease and 
the process to turn new scientific insights into products. I 
believe the need for an entity to straddle the world's research 
and industry is clear.
    In the private market, pharmaceutical companies will 
abandon drug development projects that are not initially 
successful, become too complex or do not provide a lucrative 
path forward.
    For example, since 1949, there have only been two major 
drug discoveries in mental health--lithium and Thorazine. Sixty 
years later, researchers still do not know why these drugs 
actually work. Hundreds of genes have been shown to play roles 
in mental illness, too many for focused efforts by drug 
developers.
    Therefore, many drug manufacturers have dropped out of the 
mental-health field. In particular, pharmaceuticals for rare 
and neglected disease are often ignored because private 
companies avoid this small market with little profit appeal 
leaving patients with no treatment options.
    Even promising new drugs discovered through basic research 
often struggle during the translational stage of the process 
because it's expensive, time consuming and prone to failure. 
These barriers inhibit both the scientists dedicated to 
improving health and the patients who ultimately need improved 
cures and care.
    The question remains, however, as to whether NCATS is the 
right approach to solving the issue. Will NCATS be the right 
mechanism for taking valuable discoveries that the taxpayer has 
funded and giving it a greater opportunity to make it in the 
marketplace? As we review this proposal, we need to consider 
the fact that NIH is not a drug developer or an expert in the 
therapeutics world.
    Dr. Collins, I would like to continue to work with you to 
make a thoughtful, informed decision regarding the NCATS. 
Unfortunately, the fiscal year 2012 budget request, I believe, 
does not provide adequate details on the reorganization.
    It is May 11 and we've not received a budget amendment or 
specific structural details of an NCATS, a program NIH wants to 
implement by October 1. How can the subcommittee be expected to 
support a program that does not yet exist in budget documents?
    I understand that the transition from basic research to 
clinical application requires interdisciplinary and 
multidisciplinary expertise. Research that aims to transform 
science is inherently difficult. If it were easy, the need for 
transformation would not exist.
    NCATS may be the answer to solve this complex issue, but it 
also may not be. We don't know. Dr. Collins, I believe that 
NCATS is a matter that we should contemplate, but we must 
ensure that the steps forward are measured and in the best 
interests of all stakeholders, especially those who are in need 
of treatment and care.
    I look forward to working with you and the chairman on this 
very important issue. Thank you.

                        INTRODUCTION OF WITNESS

    Senator Harkin. Thank you very much, Senator Shelby.
    Now, welcome back to Dr. Collins.
    Francis Collins was sworn in as the 16th Director of the 
National Institutes of Health in August 2009 after being 
unanimously confirmed by the Senate.
    He is a physician geneticist noted for his discoveries of 
diseased genes and leadership, of course, of the Human Genome 
Project. Prior to becoming Director, he served as Director of 
the National Human Genome Research Institute at NIH.
    Dr. Collins received his bachelor's degree from the 
University of Virginia, his Ph.D. from Yale and his M.D. from 
the University of North Carolina at Chapel Hill.
    Dr. Collins, again, welcome, and first I want to say that 
your testimony, and all of the testimony of the Directors who 
are here, will be made a part of the record in their entirety.
    Again, due to time, Dr. Collins, we ask you to make a 
fairly comprehensive statement. I'm not going to get the clock 
going here, but if it goes too long and people start looking at 
me funny, then I'll probably ask you to close it out. But 
please take whatever time you need to give us an update on NIH 
and a concise summation of your written testimony.

              SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS

    Dr. Collins. Well, thank you, Senator, and, Mr. Chairman, 
and distinguished members of the subcommittee, it's an honor to 
appear before you this morning, together with my colleagues, on 
behalf of NIH.
    And I'll try not to talk so long that people start looking 
at you or looking at me, but I do have some things I really 
wanted to put in front of this distinguished subcommittee, 
because this is a very exciting time for biomedical research.
    NIH is the largest supporter of biomedical research in the 
world, and we're here to present the President's budget request 
of $31.987 billion for fiscal year 2012.
















































































































                   NIH--Turning Discovery Into Health
 Global Competitiveness--The Importance of U.S. Leadership in Science 
      and Innovation for the Future of Our Economy and Our Health
    The National Science Board's 2010 Key Science and Engineering 
Indicators, provide insight into how crucial decisions on R&D funding 
may affect our Nation's ability to thrive in an increasingly 
competitive and knowledge-driven global economy. While these trends 
apply not just to bimoedical reserch, but also to research in 
chemistry, physics, engineering, computer science, and many other 
fields, the conclusion of most observers is that the 21st century will 
be dominated by the life sciences, and the country that leads in this 
area will have much to gain. Unfortunatley, the United States, 
traditionally the dominant Nation in scientific resarch, has been 
slipping in leadership recently.
    Losing Ground.--R&D investment growth rates are rising sharply in 
Asia.




    For example, China's growth rate is 4 times higher than the U.S. 
rate.
    While the U.S. remains among the nations with the highest actual 
R&D expenditures, Asia is rapidly closing the gap.




    Employment Impact: The number of people engaged in scientific 
research in China has increased dramatically. In 2007, China had 1.42 
million researchers, while the US had 1.47 million. In 2010, it is 
likely that China has surpassed the U.S. research workforce.




    Knowledge Generation: The number of scientific articles published 
is a common measure of scientific productivity. The average increase in 
U.S. publications is significantly lower than for other key countries 
and also below the world average. Meanwhile, China, Thailand, South 
Korea, and others show impressive growth rates.




    As a result of the previously mentioned trends, it is not 
surprising that the U.S. share of world publications has significantly 
decreased, and that China's share has grown.

------------------------------------------------------------------------
                                            Share of world
                                          articles (Percent)    Percent
             Country/Region             ----------------------   Change
                                            1998       2008
------------------------------------------------------------------------
United States..........................       34         28.9       -5.1
EU.....................................       34.6       33.1       -1.5
China..................................        1.6        5.9        4.3
Japan..................................        8.5        7.8       -0.7
Asia-8.................................        3.6        6.8        3.2
------------------------------------------------------------------------
Source: SEI 2010

    The number of times a scientific article is cited indicates its 
scientific impact. One could argue that emerging countries are 
publishing articles with limited impact. While this may be the case 
from certain perspectives, the aggregate number of citations indicates 
a worrisome plunge in the U.S. share of worldwide citations, which fell 
8.6 percent from 1998 to 2008. In contrast, China and Asia-8 countries 
displayed a noticeable increase in their share of citations, rising 3.7 
percent and 3.1 percent respectively over the same time period.
    Economic consequences: Reducing R&D investments when other nations 
are rapidly increasing them has already had significant consequences on 
exports, which are an important component of the U.S. economy and well 
being of Americans.



                        IMPACTS ON U.S. ECONOMY

    NIH is the largest funder and conductor of biomedical research in 
the world.
    The NIH fiscal year 2011 budget is $31 billion--84 percent of which 
is awarded to the Nation's finest universities, institutes, and small 
businesses through a rigorous peer review process. Every State, along 
with almost every Congressional district, benefits.
    NIH extramural program supports more than 40,000 competitive 
research grants and 325,000 research personnel at more than 3,000 
universities, medical schools, and other research institutions in all 
50 states, U.S. territories, and around the world.
    Approximately 10 percent of the NIH budget funds nearly 6,000 
scientists working at the NIH campus in Bethesda, in laboratories in 
Rockville and Frederick, Maryland, at Research Triangle Park in 
Raleigh, North Carolina, and at the Rocky Mountain Laboratories in 
Hamilton, Montana.
    NIH spending increases business activity directly and indirectly: 
According to Families USA, each dollar of NIH award money generates 
about $2.21 of new business activity within 1 year, while each grant 
awarded by NIH generates about 7 jobs.
    NIH-driven advances have not only had profound effects on the 
health and quality of life for all Americans, but also yielded economic 
gains. The percentage of elderly with chronic disabilities has declined 
(from 27 percent in 1982 to 19 percent in 2005). Since 1970, life 
expectancy in the United States has risen from 71 to 78 years. 
Economists estimate that these gains in life expectancy have been worth 
approximately $95 trillion.
    The economic potential of NIH-fueled advances in improved 
treatments for disease is also clear in this projection: a reduction in 
cancer deaths by one percent has a present value to current and future 
generations of Americans of nearly $500 billion. A full cure would be 
worth approximately $50 trillion--more than three times today's GDP.
    Advances in disease diagnosis also illustrate the health-related 
and economic benefits of NIH research: approximately $100 million in 
health care costs annually are being saved through the use of a genomic 
test that determines whether a particular type of breast cancer is 
likely to be cured by surgery and radiation or by chemotherapy. As a 
result of this test, thousands of women are being spared needless 
exposure to toxic therapies--and millions of dollars are being saved.
    NIH is an engine of innovation--and a crucial support for the 
global competitive stature of the United States. In fiscal year 2010, 
NIH filed 289 U.S. patent applications (of which 141 were new 
applications). These are now included in a total of 3,186 NIH patent 
applications in the United States and abroad that were pending 
approval.
Key Facts on U.S. Competitiveness in the Global Research Arena
    The United States still is the world leader in science and 
engineering research. But that leadership role is being challenged by 
China, India, and other nations as they recognize the economic, health, 
and social benefits of investing in R&D.
    Over the past decade, R&D intensity has grown in Asia, but remained 
flat in the United States.
    Growth of R&D expenditures in the United States averaged 5-6 
percent annually from 1996-2007, lagging behind the worldwide average 
of 7 percent per year. In contrast, growth in most Asian nations 
exceeded the worldwide average, and China's R&D expenditures grew more 
than 20 percent annually from 1996-2007.
    The United States share of high technology exports fell by one-
third from 1996-2007. China's share more than tripled.
    India exported $8.3 billion in pharmaceutical products and services 
in fiscal year 2009, up 25 percent from the previous year.
    About 277,000 people, ranging from scientists and to production 
workers, are currently employed by pharmaceutical companies in the 
United States, a decline of 5 percent from 2008. More than 340,000 
people work in India's pharmaceutical manufacturing industry in 2009--
and the industry is projected to grow by 13 percent in 2010.
    Between 1995 and 2007, the worldwide share of researchers working 
in China, Singapore, South Korea, or Taiwan rose from 16 percent to 31 
percent.
    In 2007, the United States had 1.47 million people engaged in 
scientific research; China had 1.42 million--and it was generating R&D 
jobs at three times the rate of the U.S.
    In the United States, the percentage of undergraduate students who 
major in science and engineering is 15 percent; in China, it is 50 
percent.
    In 1995, China ranked 14th in the world in the production of 
research publications. In 2008, it ranked second.
    China's leading genome sequencing institute, BGI, is on track to 
sequence more than 10,000 human genomes a year. That would surpass the 
entire DNA sequencing output of the United States.
    For more on how shifts in global research capacity are challenging 
the United States to actively focus on maintaining its competitive 
strength, go to http://www.nsf.gov/statistics/nsb1003/.



                          Health Improvements

    In the last 25 years, NIH-supported biomedical research has 
directly led to human health benefits that both extend lifespan and 
reduce illnesses:
  --Prolonging Life and Reducing Disability.--Our Nation has gained 
        about 1 year of longevity every 6 years since 1990. A baby born 
        today can look forward to an average lifespan of nearly 78 
        years--nearly three decades longer than a baby born in 1900. 
        Not only are people living longer, they are staying active 
        longer. From 1982 through 2005, the proportion of older people 
        with chronic disabilities dropped by almost a third.
  --Heart Disease.--NIH research has generated new techniques for heart 
        attack prevention, effective drugs for lowering cholesterol and 
        controlling blood pressure, and strategies for dissolving blood 
        clots. As a result, the death rate for coronary disease is 60 
        percent lower--and for stroke, more than 70 percent lower--than 
        during the era of World War II. Better treatment of acute 
        conditions, better medications, and improved health-related 
        behaviors--all made possible by NIH research--account for as 
        much as two-thirds of this reduction.
  --Chronic Disability.--From 1982-2004, the reported chronic 
        disability among American seniors dropped nearly 30 percent. 
        Health improvements from NIH research played a major role in 
        this, including better prevention and treatment of heart 
        attacks and strokes, advances in treatment of arthritis, and 
        improved technologies for cataract surgery.
  --Age-Related Macular Degeneration (AMD).--Forty years ago there was 
        little or nothing one could do to prevent or treat advanced AMD 
        and blindness. Because of new treatments and procedures based 
        on NIH research, 750,000 Americans who would have gone blind 
        over the next 5 years instead will continue to have useful 
        vision.
  --Breast Cancer.--The 5-year survival rate for women diagnosed with 
        breast cancer was 75 percent in the mid-1970s. Because of NIH-
        supported research, the 5-year survival rate has risen to over 
        90 percent.
  --Cervical Cancer.--Cervical cancer is a deadly cancer in women. Due 
        to groundbreaking NIH research, an FDA-approved vaccine 
        (Gardasil) now is available to prevent the development of 
        cervical cancer.
  --Colon Cancer.--From 1974-1976, in an NIH-sponsored study, the 5-
        year survival for patients with colon cancer was 50 percent. In 
        2009, based on NIH-supported clinical trials using new 
        diagnostics and treatments, a comparable patient group has a 5-
        year survival rate of over 70 percent.
  --Cochlear Implants.--Because of NIH-supported research, children who 
        are profoundly deaf but receive a cochlear implant within the 
        first 2 years of life now have the same skills, opportunities, 
        and potential as their normal-hearing classmates.
  --Type 1 Diabetes.--Thirty to forty years ago, 30 percent of patients 
        died within 25 years of a diagnosis of type 1 diabetes. Today, 
        due to tight blood glucose control, heart disease and stroke in 
        patient with type 1 diabetes have been reduced by over 50 
        percent.
  --Hepatitis B.--In the mid-1980s, hepatitis B infection caused 
        untreatable and fatal illness. Due to intensive vaccination 
        programs based on NIH research, the rate of acute hepatitis B 
        has fallen by more than 80 percent.
  --HIV/AIDS.--In the 1980s, the diagnosis of HIV infection was a 
        virtual death sentence. Due to antiviral drugs developed by 
        NIH, today an HIV-positive 20-year-old can be expected to reach 
        the age of 70.
  --Infant Health.--In 1976, the infant mortality rate was 15.2 infant 
        deaths per 1,000 live births. By 2006, that rate had fallen to 
        6.7 deaths per 1,000 live births. Much of this progress can be 
        attributed to NIH research in the areas of neonatal care unit 
        procedures and new drugs administered to women at risk for 
        premature birth.
  --Childhood Leukemia.--Survival rates for children with the most 
        common childhood leukemia (acute lymphocytic leukemia) is now 
        90 percent.

                         Advances In Knowledge

    NIH-funded research leads to thousands of new findings every year. 
These incremental advances and technological developments are the 
building blocks that ultimately yield significant improvements in 
health. Highlighted below are just a few of the many recent advances 
from NIH-supported research:
  --Studies find possible new genetic risk factors for Alzheimer's 
        disease.--Scientists have confirmed one gene variant and have 
        identified several others that may be risk factors for late-
        onset Alzheimer's disease, the most common form of the 
        disorder. In the largest genome-wide study, or GWAS, ever 
        conducted in Alzheimer's research, NIH-supported investigators 
        studied DNA samples from more than 56,000 study participants 
        and analyzed shared data sets to detect gene variations that 
        may have subtle effects on the risk for developing Alzheimer's. 
        Until recently, only one gene variant, Apolipoprotein E-e4 
        (APOE-e4), had been confirmed as a significant risk factor gene 
        for the common form of late-onset Alzheimer's disease, which 
        typically occurs after age 60. In 2009 and 2010, researchers 
        confirmed additional gene variants of CR1, CLU, and PICALM as 
        possible risk factors for late-onset Alzheimer's. This newest 
        GWAS confirms the fifth gene variant, BIN1, affects development 
        of late-onset Alzheimer's. The genes identified by this study 
        may implicate pathways involved in inflammation, movement of 
        proteins within cells, and lipid transport as being important 
        in the disease process.
  --NIH scientist advance universal flu vaccine.--Significant progress 
        was made toward the development of a universal flu vaccine that 
        would confer longer term protection against multiple influenza 
        virus strains. NIH-supported researchers have identified the 
        regions of influenza viral proteins that remain unchanged among 
        seasonal and pandemic strains. These findings will inform the 
        development of influenza vaccines that might one day provide 
        universal protection against the broad range of influenza 
        strains. Such a universal influenza vaccine would provide 
        broader protection against multiple flu strains and make yearly 
        flu shots a thing of the past.
  --Early detection of cancer is critical to provide effective 
        therapy.--NIH-supported investigators recently reported the 
        detection of a single metastatic cell from lung cancer in one 
        billion normal blood cells. These circulating tumor cells 
        (CTCs) may also be released into the bloodstream of patients 
        with invasive but localized cancers. The presence of CTCs may 
        be an early indicator of tumor invasion into the bloodstream 
        long before distant metastases are detected. Identifying CTCs 
        may be viewed as performing liquid biopsies, which can be 
        especially advantageous for prostate cancer. Researchers plan 
        to extend their work to develop a point-of-care microchip that 
        would allow non-invasive isolation of CTCs from patients with 
        many different types of cancer, to improve the management and 
        treatment of this devastating disease.
  --Prenatal surgery reduces complications of spina bifida.--NIH-
        supported scientists reported that a surgical procedure to 
        repair a common birth defect of the spine, if undertaken while 
        a baby is still in the uterus, greatly reduces the need to 
        divert, or shunt, fluid away from the brain. The fetal surgical 
        procedure also increases the chances that a child will be able 
        to walk without crutches or other devices. The birth defect, 
        myelomeningocele, is the most serious form of spina bifida, a 
        condition in which the spinal column fails to close around the 
        cord. The study, the Management of Myelomeningocele Study 
        (MOMS), was stopped after the enrollment of 183 women, because 
        of the benefits demonstrated in the children who underwent 
        prenatal surgery. In spite of an increased risk for preterm 
        birth, children who underwent surgery while in the uterus did 
        much better, on balance, than those who had surgery after 
        birth.
  --Progesterone reduces rate of early preterm birth in at risk 
        women.--Preterm infants are at high risk of early death and 
        long term health and developmental problems including, 
        breathing difficulties, cerebral palsy, learning disabilities, 
        blindness and deafness. An NIH study found that progesterone 
        gel reduces the rate of preterm birth before the 33rd week of 
        pregnancy by 45 percent among women with a short cervix, which 
        is known to increase the risk of preterm birth. Women with a 
        short cervix can be identified through routine ultrasound 
        screening, and once identified could be offered treatment with 
        progesterone. In addition, infants born to women who received 
        progesterone had a lower rate of respiratory distress syndrome 
        than those in the placebo group.
  --Daily dose of HIV drug reduces risk of HIV infection.--A daily dose 
        of an oral antiretroviral drug, currently approved to treat HIV 
        infection, was shown to reduce the risk of acquiring HIV 
        infection by 43.8 percent among men who have sex with men. The 
        findings, a major advance in HIV prevention research, came from 
        a large international clinical trial supported by NIH. The 
        study, titled ``Chemoprophylaxis for HIV Prevention in Men'' 
        found even higher rates of effectiveness, up to 72.8 percent, 
        among those participants who adhered most closely to the daily 
        drug regimen. These new findings provide strong evidence that 
        pre-exposure prophylaxis with an antiretroviral drug, a 
        strategy widely referred to as PrEP, can reduce the risk of HIV 
        acquisition among men who have sex with men, a segment of the 
        population disproportionately affected by HIV/AIDS. 
        Prophylactic antiretroviral therapy has already been proven to 
        significantly reduce the transmission of HIV from a mother to a 
        child during childbirth through breastfeeding.
  --Pocket-sized device makes medical ultrasound more accessible.--NIH-
        supported research at General Electric supported the 
        development of a low-cost, portable, high-quality ultrasonic 
        imager. In the last year, this advance was extended even 
        further with GE's production of ``Vscan.'' This pocket-sized 
        device makes medical ultrasound even more accessible and has 
        enabled wireless imaging, patient monitoring, and prenatal care 
        applications.

        
        

  --Lung cancer screening with CT scan reduces deaths.--The National 
        Lung Screening Trial found that screening with low-dose 
        computed tomography (CT) can decrease lung-cancer deaths among 
        current and former heavy smokers by 20 percent. Because of 
        earlier identification of cancerous tumors, screening was found 
        to reduce mortality from lung cancer, the most common cause of 
        cancer deaths.
  --Nicotine vaccine shows promise in preventing tobacco addiction.--
        Vaccines developed to combat drug addictions work by generating 
        drug-specific antibodies that bind the drug while in the 
        bloodstream and prevent its entry into the brain. A nicotine 
        vaccine recently found to improve smoking quit rates is now in 
        phase III trials to evaluate continued abstinence at 12 months.
  --Nanotechnology demonstrates advances in the realm of materials 
        technologies.--Carbon nanotubes have been used to deliver 
        chemotherapeutic agents specifically to head and neck cancer 
        cells, causing rapid death of the cancer cells, but leaving 
        non-cancerous cells unharmed.
  --Certain lipid molecules that show promise in controlling pain could 
        result in new treatments.--Researchers have demonstrated in 
        animal models that certain lipids called resolvins, which shut 
        down inflammation, are more potent than morphine in controlling 
        pain. Since these resolvins are normally found in the body, 
        they are likely to be safe and non-addictive when used 
        therapeutically. Additional research is under way to explore 
        these compounds further and translate into new analgesics for 
        pain management.
  --Combined treatment improves vision in patients with diabetic 
        macular edema.--A comparative effectiveness study for diabetic 
        macular edema found that combined treatment with the drug 
        ranibizumab and laser therapy was substantially better at 
        improving vision in patients with diabetes than laser therapy 
        alone, and better than laser therapy with a different drug 
        (triamcinolone).
  --Scientists develop a system for making functional hair cells from 
        stem cells, offering possible new treatment of deafness.--In 
        mammals, mechanically-sensitive ``hair cells'' in the inner 
        ear, which are essential for both hearing and balance cannot 
        regenerate when they die or are damaged. NIH supported 
        scientists have used mouse embryonic stem cells as well as 
        induced pluripotent stem cells and generated hair cells that 
        respond to mechanical stimulation, offering a new avenue for 
        the treatment of deafness.
  --Experimental medication lifts depression symptoms in people with 
        bipolar disorder.--NIH intramural researchers discovered that 
        ketamine, an anesthetic medication, provides rapid and 
        effective treatment for depressive symptoms among patients with 
        bipolar disorders. While ketamine's side effects make it 
        impractical for long-term use, this class of drugs may be 
        invaluable for treating severe depressive symptoms in these 
        patients during the weeks it usually takes for typical 
        antidepressants to take full effect.

     Proposed National Center for Advancing Translational Sciences
                     National Institutes of Health

Rationale
    The development of new diagnostics and therapeutics is widely 
recognized as a complex, costly, and risk-laden endeavor. Only a few of 
the thousands of compounds that enter the drug development pipeline 
will ultimately make it into the medicine chest.

    ----------------------------------------------------------------

                                Mission

    To advance the discipline of translational science and catalyze 
development and testing of novel diagnostics and therapeutics across a 
wide range of human diseases and conditions.

    ----------------------------------------------------------------

    In recent years, there has been a deluge of new discoveries of 
potential drug targets, yet we still lack effective therapeutics for 
many conditions, especially rare and neglected diseases. A major 
problem is that the drug development pipeline is full of bottlenecks 
that slow the speed of development and add expense to the process. To 
address these challenges, the National Institutes of Health (NIH) has 
proposed establishing the National Center for Advancing Translational 
Sciences (NCATS).




    NCATS will study various steps in the drug development pipeline, 
identify bottlenecks amenable to re-engineering, and experiment with 
innovative methods to streamline the process. Promising therapeutic 
projects will be used to evaluate pipeline innovations.
    NCATS will complement--not compete with-- translational research 
being carried out elsewhere at NIH and in the private sector. In fact, 
through its mission to use the power of science to advance the entire 
discipline, NCATS will benefit all stakeholders, including academia, 
biotechnology firms, pharmaceutical companies, the Food and Drug 
Administration, and--most importantly--patients and their families.
Functions
    NCATS will aim to improve the processes in the drug development 
pipeline by:
  --experimenting with innovative approaches in an open-access model;
  --choosing therapeutic projects to evaluate these innovative 
        approaches; and
  --promoting interactions to advance the field of regulatory science.
    NCATS also will strive to catalyze the development of new drugs and 
diagnostic tests by:
  --encouraging collaborations across all sectors;
  --providing resources to enable therapeutic development; and
  --enhancing training in relevant disciplines.

    ----------------------------------------------------------------

    NCATS will:
  --facilitate--not duplicate--other translational research activities 
        supported by NIH;
  --complement--not compete with--the private sector; and
  --reinforce--not reduce--NIH's commitment to basic research.

    ----------------------------------------------------------------

Programs
    NCATS will be formed by pulling together these existing NIH 
programs: components of the Molecular Libraries initiative, 
Therapeutics for Rare and Neglected Diseases, Office of Rare Diseases 
Research, Rapid Access to Interventional Development, Clinical and 
Translational Science Awards, and FDANIH Regulatory Science. In 
addition, the Cures Acceleration Network will be part of NCATS if funds 
are appropriated for fiscal year 2012. Relocated programs will have 
their respective budgets transferred to the new center.

    Background
    On May 19, 2010, the NIH Director asked the NIH Scientific 
Management Review Board (SMRB) to:
  --identify the attributes, activities, and functional capabilities of 
        a translational medicine program for advancing therapeutics 
        development; and
  --broadly assess the NIH landscape for existing programs, networks, 
        and centers for inclusion; and recommend their optimal 
        organization.

        
        

    On Dec. 7, 2010, the SMRB recommended the creation of a new 
translational medicine and therapeutics center. It also urged NIH to 
undertake a detailed analysis, through a transparent process, to 
evaluate the new center's impact on existing NIH programs.
    Informed by the SMRB's recommendations, NIH initiated a planning 
process to establish NCATS. The NIH Director established three panels 
to guide and inform the process: the Institute and Center Directors' 
(ICD) NCATS working group, the Advisory Committee to the Director (ACD) 
NCATS working group, and the NIH Clinical and Translational Science 
Awards (CTSA) Integration working group.
    On Jan. 4, 2011, Dr. Collins charged the ICD working group with 
making recommendations on the mission, functions, and organizational 
design of NCATS. This panel presented its recommendations to Dr. 
Collins on Feb. 17, 2011. The ACD working group, which has been asked 
to provide high-level advice on how NCATS can best engage the private 
sector in translational science, met for the first time on Feb. 4, 
2011. This distinguished panel of outside experts will report its 
findings to the ACD later this year.
    The final working group, composed of leaders from across NIH, was 
formed in mid-March to ensure a smooth transition of the CTSA program 
into NCATS.

Next Steps
    At every point along the way, NIH has sought input on NCATS from a 
broad and diverse array of stakeholders. In addition, NIH will continue 
to inform all stakeholders on new developments and seek their comments 
through our interactive web site Feedback NIH.
    Pending approval from the Health and Human Services Secretary, the 
Office of Management and Budget, and the Congress, NCATS will be 
included in the fiscal year 2012 budget and be formally established on 
Oct. 1, 2011.

    So in this brief statement today, I'd like to tell you 
about four innovative areas, and I'm going to show some 
pictures up on the screen in which NIH is investing in order to 
carry out its mission of turning discovery into health.
    First, dramatic advances in technologies, including 
imaging, nanotechnology, computational biology, and, yes, 
genomics, have recently made it possible for scientists to 
understand the details of health and disease in breathtaking 
new ways.
    Consider this curve, the cost to sequence a human genome. 
Look at the profound reduction over the past decade. In 2001, 
it cost about $100 million to sequence a single human genome. 
That cost now stands at about $10,000, and we anticipate it 
will be less than $1,000 within the next few years.
    That advance will give many Americans access to far more 
personalized strategies for detecting, treating and preventing 
disease than are now available.
    Those new technologies not only reduce the cost of doing 
science, but open up whole new frontiers in medicine. I'll tell 
you about one of those later in a story about a 6-year-old boy 
named Nic that I think you'll find quite compelling.
    But, first, let's turn to the effects that this technology 
has had on our understanding of cancer. Cancer is a disease of 
the genome, comes about because of mutations in DNA.
    Through a bold initiative, called the Cancer Genome Atlas, 
or TCGA, my colleague, Harold Varmus, and others are analyzing 
the DNA of tumors of hundreds of patients to identify 
comprehensively the genetic mutations associated with the 
specific cancers.
    Brain and ovarian cancers were the first ones selected for 
study through TCGA and the results have been stunning. Knowing 
the molecular drivers of cancer gives us a chance to make much 
more accurate diagnoses, prognoses, and predictions of response 
to therapy. And in the longer run, this approach will lead to 
development of a new generation of targeted therapies, those 
magic bullets so dreamed of to treat this disease.
    The plan for the next few years is ambitious. TCGA will 
sequence, characterize, and understand the genomes of 20 
different types of tumors.
    New treatments are wonderful. Effective prevention can be 
even better. NIH is dedicated to use the latest science to 
improve America's health today by identifying effective new 
strategies for disease prevention. The grave threat of diabetes 
is a compelling example of how we are doing this.
    This map shows the prevalence of diabetes in the United 
States in 1995. As you can see from the color code, in most 
States, less than 5 percent of adults were affected, but watch 
what happened over just 15 years. Prevalence of diabetes has 
gone up rapidly in every State, and it now stands at 9 percent 
or more in many parts of the country.
    The total costs of the disease, including medical care, 
disability and premature death, were an estimated $174 billion 
in the United States in 2007. If current trends continue, one 
in three U.S. adults will have diabetes by 2020, just 9 years 
from now, and the annual cost of care alone will have risen to 
a breathtaking $500 billion.
    But my colleague, Grif Rodgers, and I can offer some hope. 
NIH spearheaded a landmark clinical trial on how to prevent 
type 2 diabetes. The Diabetes Prevention Program, or DPP, 
involved adults with pre-diabetes. That refers to a modest 
elevation of glucose in the blood foreshadowing much worse to 
come if nothing is done, but not yet frank diabetes.
    The study participants were assigned personal coaches who 
encouraged them to exercise about 30 minutes a day and to make 
modest dietary changes resulting in an average weight loss of 
just 7 percent. This simple approach lowered the chance of 
full-blown diabetes by a whopping 58 percent, and that has been 
sustained for more than 10 years.
    Building on these results, NIH has joined with the Centers 
for Disease Control and Prevention (CDC), the YMCA, Walgreens, 
United Health Care and other partners to bring this program to 
communities in 10 States. And we are now working with 
colleagues at CMS to explore how a similar program could be 
used to great advantage in Medicare and Medicaid.
    Now, I'd like to turn your attention to another important 
contribution of NIH research already mentioned by the chairman, 
enhancing the economy and U.S. competitiveness worldwide.
    NIH will be a key engine driving the U.S. economy in the 
21st century. Many call this the century of biology. As 
mentioned, just yesterday, a new economic impact study 
published by United for Medical Research suggests that in 
fiscal year 2010 NIH research funding supported an estimated 
487,900 American jobs at 3,000 institutions and small 
businesses across all 50 States of this Nation.
    More than that, nearly 1 million U.S. citizens are employed 
by the industries and companies that make up this sector of the 
economy, earning $84 billion in wages and salary and exporting 
$90 billion of goods and services annually. But despite this 
impressive track record, our Nation today is at serious risk of 
losing its position as the world's research leader.
    As you can see in this slide, which shows the percent 
growth of R&D expenditures on an annual basis, China and India 
and other countries have been steadily increasing their R&D 
expenditures by 10 percent or more per year, highlighting China 
and India there. Whereas, the United States has been at a 
substantially lower level. China's growth rate is now four 
times greater than ours.
    Let me give you a personal example of what this means. Last 
fall, when I visited the BGI Genome Center in Shenzhen, China, 
I saw an amazing facility built in just 3 years from an 
abandoned shoe factory that is capable of sequencing more than 
10,000 human genomes a year.
    The capacity of that one Chinese institution now surpasses 
the combined capacity of all genome sequencing centers in the 
United States. This critical area of scientific innovation, 
stimulated by the U.S.-led Human Genome Project, is now being 
developed more aggressively in China than it is here, a 
sobering story indeed, and one that I hope would inspire our 
Nation to redouble its efforts on the research front.
    A final area I wish to highlight in which our Nation faces 
exceptional challenges, as well as exceptional opportunities, 
is this field of translational science which Senator Shelby has 
specifically highlighted in his opening statement. As a result 
of years of steadfast support of NIH research by Congress and 
the American people, we find ourselves in a paradoxical 
situation.
    This graph shows we've seen a deluge of discoveries about 
the molecular basis of disease, both rare and common, which 
provide us with the power to identify more therapeutic targets 
than ever before; more than 4,000 diseases now having their 
molecular basis discovered, much of that in the last decade.
    But there's a serious problem. The process of taking those 
basic discoveries to the point of clinical advances, as here 
demonstrated by a diagram showing you what happens in the 
development of new therapeutics, is far too slow--14 years on 
the average--and the failure rate is far too high--more than 98 
percent. We clearly need a new approach to therapeutic 
development and a new partnership with the private sector.
    So to meet this need, NIH is proposing the establishment of 
a new national center for advancing translational sciences or 
NCATS. NCATS will allow us to study the various steps in the 
development of diagnostics, devices and therapeutics, identify 
bottlenecks that might be reengineered and experiment with 
innovative methods to streamline this process.
    Through this new center, we can work in an open-access 
model that will allow stakeholders, including industry and 
academia, to access and apply the innovations that are 
developed. NCATS will also advance the field of regulatory 
science by promoting interactions among the NIH, FDA, patient 
advocates, and pharmaceutical and biotechnology companies.
    Importantly, NCATS will complement, not compete with, the 
private sector. This is not Bethesda Pharm. It will facilitate 
translational research being carried out elsewhere at the NIH, 
extensive translational work already going on by many of the 27 
Institutes, including those represented at this table. And it 
will reinforce, not reduce, NIH's commitment to basic science, 
a foundational part of our mission.
    Most importantly, though, by advancing discipline of 
translational sciences, NCATS will benefit patients and their 
families.
    So, Mr. Chairman, members of the subcommittee, I've spoken 
today about the great promise of new technologies, how we're 
applying science to prevention, NIH's role in maintaining U.S. 
economy--world leadership, and the unique opportunity to pursue 
a new paradigm in translation.
    Let me close by sharing the story of one little boy to show 
you what NIH research advances now allow us to do. So meet Nic 
Volker, a brave boy from Monona, Wisconsin.
    Starting about the age of two, Nic developed a mysterious 
life-threatening disease that ravaged his body, making it 
impossible for him to eat normally and causing unimaginable 
pain and suffering.
    At a loss to explain Nic's terrible affliction, researchers 
at the Medical College of Wisconsin decided to sequence Nic's 
DNA instruction book hoping to find an answer. After exacting 
work over several months, the researchers identified a 
misspelling of just one single letter in a little-studied gene 
called XIAP. Now, glitches in this gene had been associated 
with rare blood disorders, but not with intestinal symptoms. 
Based on this new insight, the research team had an idea that, 
as with the rare blood disorders, Nic's disease might be 
curable with a bone-marrow transplant.
    Transplantation of cord blood cells from--stem cells from a 
matched donor occurred in July of last year. Although Nic is 
still receiving some immunosuppressant drugs to prevent 
rejection of the donated cells, his symptoms have largely 
disappeared, and, today, as you can see here, he can eat 
normally and vigorously.
    What's more, he's now attending kindergarten, enjoying 
outings with his family and friends, signing up for a T-Ball 
team, and, this past Sunday, presenting his mother with a 
flower for Mother's Day. Nic has given us all a glimpse of the 
future.

                          PREPARED STATEMENTS

    Thank you, Mr. Chairman. This concludes my formal remarks.
    [The statements follow:]

         Prepared Statement of Francis S. Collins, M.D., Ph.D.

                              INTRODUCTION

    Good morning, Mr. Chairman and distinguished Members of the 
Subcommittee. I am Francis S. Collins, M.D., Ph.D. and I am Director of 
the National Institutes of Health (NIH).
    It is a great honor to appear before you today to present the 
administration's program level request of $31.987 billion for NIH in 
fiscal year 2012, and to discuss the contributions that NIH-funded 
biomedical research has made in improving human health. NIH is the 
largest supporter of biomedical research in the world, providing funds 
for more than 40,000 competitive research grants and more than 325,000 
research personnel at more than 3,000 research institutions and small 
businesses across our Nation's 50 States. I also want to offer a vision 
of how NIH will catalyze innovation in basic and translational 
sciences, and will ensure future U.S. economic strength and global 
competitiveness.
    On behalf of NIH and the biomedical research enterprise, I want to 
thank you as Members of the Senate for sparing NIH from deeper cuts in 
the final fiscal year 2011 continuing resolution (CR). We know that, 
even as Congress and the administration wrestled with cuts of more than 
3 percent to the Labor-HHS portion of the CR, NIH received a 1 percent, 
or $321.7 million, cut from the fiscal year 2010 level, while other 
programs and functions were cut more deeply.
    NIH's mission is to seek fundamental knowledge about the nature and 
behavior of living systems and to apply that knowledge to enhance human 
health, lengthen life, and reduce the burdens of illness and 
disability. I can report to you that NIH continues to believe 
passionately in that mission and works tirelessly to achieve it.
    Due in large measure to NIH research, our Nation has gained about 1 
year of longevity every 6 years since 1990. A child born today can look 
forward to an average lifespan of nearly 78 years--nearly three decades 
longer than a baby born in 1900. And not only are people living longer, 
but their quality of life is improving: in the last 25 years, the 
proportion of older people with chronic disabilities has dropped by 
almost one-third.
    NIH research has enabled new techniques to prevent heart attacks, 
newer and more effective drugs for lowering cholesterol and controlling 
blood pressure, and innovative strategies for dissolving blood clots 
and preventing strokes. As a result, the U.S. death rate for coronary 
disease is 60 percent lower--and for stroke, more than 70 percent 
lower--than three generations ago. Better treatment of acute heart 
disease, better medications, and improved health-related behaviors--all 
underpinned by NIH research--account for as much as two-thirds of these 
reductions.
    In recent years, largely as a result of NIH research, we have 
succeeded in driving down mortality rates for cancer in the United 
States. This progress comes despite the fact that cancer is largely a 
disease of aging and our population is growing older. Over the 15-year 
period from 1992 to 2007, cancer death rates dropped 13.5 percent for 
women and 21.2 percent for men. According to an American Cancer Society 
report released in July 2010, the continued drop in overall mortality 
rates over the last 20 years has saved more than three-quarters of a 
million lives.\1\ And in cancers that strike children we have made 
near-miraculous progress--the 5-year survival rate for children with 
the most common childhood cancer, acute lymphocytic leukemia, is now 90 
percent.\2\
---------------------------------------------------------------------------
    \1\ http://pressroom.cancer.org/index.php?s=43&item=252.
    \2\ http://seer.cancer.gov/csr/1975_2008/
browse_csr.php?section=28&page=sect_28_table.08.html.
---------------------------------------------------------------------------
    I would also like to offer a shining example of the Senate's strong 
and consistent support of biomedical research at NIH by note that we 
are celebrating a significant anniversary. This year marks the 10th 
anniversary of the establishment of the Dale and Betty Bumpers Vaccine 
Research Center (VRC) at NIH. Groundbreaking research performed at the 
VRC is making great progress toward developing a universal flu vaccine 
that confers longer-term protection against seasonal and pandemic 
influenza strains.
    Today, scientists have to make an educated guess about the make-up 
of the coming winter's influenza viruses. These educated guesses become 
the basis for the manufacture of each year's flu shot and mean that 
everyone has to be re-immunized in anticipation of next year's strain 
of flu. Recently, NIH scientists have identified pieces of influenza 
viral proteins that consistently appear among seasonal and pandemic flu 
strains. These findings raise the possibility that we might soon 
develop an influenza vaccine that provides near-universal protection 
against a broad range of current and future strains of influenza,\3\ as 
well as make yearly flu shots a thing of the past. Most of this 
exciting work was performed at the VRC. Scientists at that same center 
are making important strides toward the development of the long-hoped-
for vaccine against the human immunodeficiency virus (HIV), the cause 
of acquired immune deficiency syndrome (AIDS). While after so many 
frustrations, no one would want to predict success just yet, recent 
discoveries of VRC scientists about how to encourage production of 
neutralizing antibodies against HIV have provided renewed hope that 
this pressing problem may ultimately be solved.
---------------------------------------------------------------------------
    \3\ http://www.niaid.nih.gov/news/newsreleases/2010/Pages/
UniversalFluVax.aspx.
---------------------------------------------------------------------------
                        NIH AND ECONOMIC GROWTH

    Mr. Chairman and Members of the Subcommittee, I recognize that, 
given our Nation's fiscal situation, and the extraordinarily tough 
decisions that you will have to make about our Nation's finances, you 
need to be assured that NIH remains a worthwhile national investment. 
Even as you make these decisions and even as our country recovers from 
financial recession, I want to offer evidence that NIH and its research 
provide two strong and ongoing benefits to our economy.
    First, NIH research spending has an impact on job creation and 
economic growth. A new economic impact study by United for Medical 
Research suggests that in fiscal year 2010, NIH research funding 
supported an estimated 487,900 American jobs, including researchers and 
spin-off employment.
    Second, NIH research funding has a longer term impact in its role 
as the foundation for the medical innovation sector. Nearly 1 million 
U.S. citizens are employed by the industries and companies that make up 
this sector of the economy, earning $84 billion in wages and salary in 
2008, and exporting $90 billion of goods and services in 2010. NIH 
support for biomedical research institutions catalyzes business 
activity in other ways as well. Such institutions constitute reservoirs 
of skilled, knowledgeable individuals and, thereby, attract companies 
that wish to locate their operations within such ``knowledge hubs.''
    For example, in the 1990s, Federal funding through research grants 
and the Small Business Innovation Research (SBIR) and the Small 
Business Technology Transfer (STTR) programs transformed the academic 
research environment and helped to launch new industrial sectors in 
Silicon Valley and elsewhere that are flourishing today. Federal 
funding has been crucial in stimulating the formation of start-up 
companies and collaborations among academia and the private sector in 
the development of innovative technology. A prime example is the 
company Affymetrix.
    In the late 1980s, a team of scientists led by Stephen P.A. Fodor, 
Ph.D., developed methods for fabricating DNA microarrays, called 
GeneChips, using semiconductor manufacturing techniques, melded with 
advances in combinatorial chemistry to capture vast amount of 
biological data on a small glass chip. In 1992, the first of several 
NIH grants was awarded to Affymetrix; with this and an SBIR grant from 
the Department of Energy, Dr. Fodor was able to demonstrate proof of 
principle of using large arrays of DNA probes in genetic analysis. 
Affymetrix and similar companies are building the machine tools of the 
genomic revolution. In 2009, Affymetrix had annual revenue of $327 
million and employed more than 1,100 people.
    Furthermore, NIH research leads to better health outcomes that not 
only ease human suffering, but also produce an economic return. A 2006 
study by Kevin Murphy and Robert Topel of the University of Chicago 
shows that a permanent reduction of 1 percent in cancer deaths has a 
present value to current and future generations of Americans of nearly 
$500 billion. The article states that if we were able to defeat cancer 
completely, such cures would be worth approximately $50 trillion--more 
than three times today's Gross Domestic Product.\4\
---------------------------------------------------------------------------
    \4\ Murphy, K.M., & Topel, R.H. (2006), The value of health and 
longevity. Journal of Political Economy, 114(5), 871-904.
---------------------------------------------------------------------------
    We face a similar economic threat from diabetes. If current trends 
continue, by 2050 as many as one in three U.S. adults will be diagnosed 
with diabetes.\5\ Total costs of diabetes, including medical care, 
disability, and premature death, reached an estimated $174 billion in 
the United States in 2007.\6\ According to analysis from the 
UnitedHealth Center for Health Reform & Modernization, more than 50 
percent of Americans could have diabetes or pre-diabetes by 2020.\7\ 
Furthermore, the center's analysis predicts diabetes and pre-diabetes 
will account for an estimated 10 percent of total healthcare spending 
by the end of this decade, at an annual cost of almost $500 billion.
---------------------------------------------------------------------------
    \5\ http://www.cdc.gov/media/pressrel/2010/r101022.html.
    \6\ CDC National Diabetes Fact Sheet. http://www.cdc.gov/diabetes/
pubs/pdf/ndfs_2011.pdf.
    \7\ http://www.unitedhealthgroup.com/hrm/UNH_WorkingPaper5.pdf.
---------------------------------------------------------------------------
    But I can offer some hope. NIH spearheaded a landmark clinical 
trial on type 2 diabetes prevention that showed that people at high-
risk for diabetes can dramatically reduce their risk of developing type 
2 diabetes through modest exercise and dietary changes that achieve 
modest weight loss. Called the Diabetes Prevention Program (DPP), the 
clinical trial included 3,234 adults at high risk for developing type 2 
diabetes, including those with a family history of diabetes, as well as 
other risk factors. One-third of these individuals participated in a 
lifestyle program that included exercise training and dietary change 
implemented under the guidance of lifestyle coaches. The DPP research 
team found that this approach lowered risk of diabetes by 58 
percent.\8\ The DPP trial also demonstrated that the cost of the 
lifestyle intervention was $3,540 per participant over 3 years, which 
was significantly offset by the lowering of other healthcare costs as 
lifestyle participants became healthier.\9\ The cost effectiveness of 
the DPP has continued to be followed and 10-year results will be 
published in the near future. Building on these critically important 
results, NIH partnered with the Centers for Disease Control and 
Prevention (CDC) and more than 200 private partners, including the 
YMCA, Walgreens, and UnitedHealthcare, to bring these evidence-based 
lifestyle interventions to communities in Ohio, Indiana, Minnesota, 
Arizona, Oklahoma, New Mexico, New York, New Jersey, Connecticut, and 
Georgia. In addition, the DPP Lifestyle Intervention is being used by 
the Indian Health Service in a large demonstration project on many 
American Indian reservations.
---------------------------------------------------------------------------
    \8\ Knowler WC, et al. Reduction in the incidence of type 2 
diabetes with lifestyle intervention or metiformin. N. Engl J Med 
346:393-403, 2002.
    \9\ Diabetes Care. 2003 Jan;26(1):36-47.
---------------------------------------------------------------------------
                       INVESTING IN BASIC SCIENCE

    At NIH, we have always put our greatest percentage of our resources 
into basic research. This is because the fundamental observations made 
today become the building blocks of tomorrow's knowledge, therapies, 
and cures. NIH's history has repeatedly demonstrated that significant 
scientific advances occur when new basic research findings, often 
completely unexpected, open up new experimental possibilities and 
therapeutic pathways. Historically, NIH has put more than 50 percent of 
its budget into basic research and the research discoveries that led to 
the 132 Nobel prizes won by our intramural and university scientists 
are evidence of the wisdom of this investment.
    Basic research is precisely the type of work that the private 
sector, which must see a rapid return on invested capital, cannot 
afford to support. NIH provides the fundamental observations that 
pharmaceutical and biotechnology companies can turn into diagnostics, 
therapies, and devices that eventually reach patients. As the 
Congressional Budget Office put it, ``Federal funding of basic research 
directly stimulates the drug industry's spending . . . by making 
scientific discoveries that expand the industry's opportunities for 
research and development.'' \10\
---------------------------------------------------------------------------
    \10\ Congressional Budget Office, Research and Development in the 
Pharmaceutical Industry, October, 2006, p. 3.
---------------------------------------------------------------------------
    Because we simply cannot predict the next scientific revelation or 
anticipate the next opportunity, our basic research portfolio must be 
diverse. We set scientific priorities by considering a wide array of 
biomedical questions that we might try to answer. It is rather like 
facing a series of doors, some of which lead to vast treasures and 
others to much more modest payouts, without any sure way of knowing 
what lies behind any particular door. To improve our odds of striking 
scientific gold, we need a broad basic research portfolio that enables 
our Nation to open as many doors as our resources allow.
    Not all disease or scientific problems are equally ripe for new 
advances, nor do such advances come at the same rate across the 
portfolio, no matter how pressing today's public health challenges are. 
We can only be sure that without a strong commitment to basic research 
today, the new knowledge of tomorrow will remain hidden behind those 
unopened doors and future therapies and cures will remain out of our 
reach.
    Let me offer a few of the exciting insights that NIH's support of 
basic research have provided. On April 3, 2011, the online issue of 
Nature Genetics presented the findings by a team of NIH-supported 
scientists who had identified five new genetic variants that are risk 
factors for late-onset Alzheimer's disease, which is the most common 
form of the disorder. These findings doubled from 5 to 10 the number of 
gene variants that we know are associated with Alzheimer's disease.\11\
---------------------------------------------------------------------------
    \11\ Naj, A.C. et al. Common Variants of MS4A4/MSA6E, CD2AP, CD33 
and EPHA 1 are associated with late-onset Alzheimer's Disease. Nature 
Genetics, EPUB April 3, 2011, and Holligworth, P., et al. Common 
variants at ABCA7, MS4A/MS4A4E, EPHA 1, CD33 and CD2Ap are associated 
with Alzheimer's disease. Nature Genetics. Epub April 3, 2011.S
---------------------------------------------------------------------------
    What is even more compelling is that these newly identified genes 
strongly implicate inflammation and high cholesterol as risk factors in 
the development of Alzheimer's disease. Although each of these newly 
identified genes increases a given individual's risk of developing the 
disease by no more than 10 to 15 percent, the unanticipated insight 
that cholesterol and inflammation are contributing factors opens up new 
research avenues to understand the disease process, and increases the 
likelihood that we can glimpse potential preventions or therapies.
    NIH's commitment to basic research has also provided us with one of 
the most promising therapeutic strategies we have seen to date for the 
deadliest form of skin cancer, melanoma. Since 2002, we have known that 
many melanoma tumors exhibit a mutation in the BRAF gene and that this 
mutation might provide a target for therapeutic intervention. A team 
that included NIH-supported investigators used high-throughput 
screening in combination with structural biology, to identify compounds 
that inhibit the activity of the mutant form of the BRAF gene found in 
most melanomas, but have little effect on the BRAF gene found in normal 
cells. This basic cancer research supported by NIH contributed to the 
development of the drug PLX4032, a drug designed to inhibit the 
activity of a mutant form of the protein called BRAF. This is a 
powerful example of how support for basic research can be translated 
into therapeutic potential. In August 2010, Plexxikon, a small drug 
development company, announced that PLX4032, had elicited a positive 
response in more than 80 percent of melanoma patients in early phase 
clinical trials. PLX4032 caused the tumors in 24 of the 30 trial 
participants to shrink by at least 30 percent, while the tumors of two 
patients disappeared. Another clinical trial involving hundreds of 
participants across many institutions demonstrated that metastatic 
melanoma patients treated with PLX4032 lived 6 to 8 months longer than 
those who had been given the chemotherapy drug dacarbazine, which is 
the current standard of care.
    Whether it is with the hope of finding new ways to treat cancer, 
prevent Alzheimer's disease, or help people suffering from countless 
other rare and common conditions, we at NIH invest in basic research 
because of our conviction that it will benefit our Nation in the long 
term.

                    ADVANCING TRANSLATIONAL SCIENCE

    NIH also has a longstanding commitment to translating fundamental 
knowledge into cures and therapies for human disease. It should not be 
surprising that NIH-supported science underpins many of the most 
transformative drugs and therapies that have benefited millions of 
Americans and people around the world, including statins to lower 
cholesterol and drugs to treat depression. In 2010, we conducted a 
trans-NIH inventory of therapeutics development activities and found 
more than 550 such projects, of which approximately 65 percent were 
pre-clinical and 35 percent were clinical research.
    An analysis published in the February 10, 2011 issue of the New 
England Journal of Medicine (NEJM) underscores the depth and breadth of 
NIH's support for translational science that benefits patients.\12\ The 
article's authors describe a new emphasis on ``public sector research'' 
that is almost exclusively supported or conducted by NIH, noting ``the 
boundaries between the roles of the public and private sectors have 
shifted substantially since the dawn of the biotechnology era, and the 
public sector now has a much more direct role in the applied-research 
phase of drug discovery.''
---------------------------------------------------------------------------
    \12\ Stevens, Ashley J. et al. The role of public-sector research 
in the discovery of drugs and vaccines. New England Journal of 
Medicine, 364,:6, February 10, 2011.
---------------------------------------------------------------------------
    Drugs that represent a major advance in treatment or offer 
treatments for diseases for which no adequate therapy currently exists 
are granted ``priority review'' by FDA. According to the NEJM article, 
between 1990 and 2007, 20 percent of the FDA approvals of novel 
compounds granted priority review were given to drugs discovered by 
NIH. Examples include AZT for HIV/AIDS and the targeted leukemia 
therapy Gleevec. Over the past 40 years, 153 new FDA-approved drugs, 
vaccines, or new indications for existing drugs were discovered through 
work carried out by NIH-supported biomedical research institutions.
    Despite NIH's historic and growing commitment to translational 
sciences, far more remains to be done. Millions of people still suffer 
from diseases, such as cancers and diabetes, for which we have no 
adequate treatments. There are nearly 7,000 rare diseases, yet we have 
therapies for fewer than 200 of them. This staggering public health 
need and attendant human suffering continues even as the pharmaceutical 
industry, beset by economic stress, is investing less in research and 
development, and the pool of venture capital needed by the biotech 
industry is drying up.
    At the same time, a deluge of discoveries about the molecular basis 
of disease has been made possible by the sequencing of the human and 
many other genomes, as well as breathtaking advances in research 
technologies, such as high-throughput screening and bioinformatics. 
These discoveries reveal hundreds of tantalizing potential therapeutic 
targets. As the result of years of steadfast support of NIH research by 
Congress and the American people, we find ourselves in a paradoxical 
situation: we can uncover the molecular basis of common and rare 
diseases better than ever before and we can more readily identify 
therapeutic opportunities than at any point in history, but the 
pipeline through which these new therapeutic agents must pass is 
crimped and, in some places completely blocked.
    Consequently, a new approach to therapeutic development, and a new 
partnership with the private sector, is needed. That is why we have 
proposed the establishment of NIH's new National Center for Advancing 
Translational Sciences beginning in fiscal year 2012.

          NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

    As previously noted, NIH has a long and rich history of significant 
contributions to therapeutic development. In particular, the National 
Cancer Institute (NCI) and the National Institute for Allergy and 
Infectious Diseases (NIAID) have made major contributions over many 
years to the discovery of new treatments. However, now is the time to 
consider the therapeutic development process itself as a scientific 
problem that is ripe for innovation. The mission of the National Center 
for Advancing Translational Sciences (NCATS) will be to advance the 
discipline of translational science and catalyze the development and 
testing of novel diagnostics and therapeutics across a wide range of 
human diseases and conditions. NIH has no intention of entering the 
drug development arena that is rightly the province of private sector 
companies. Indeed, given that it costs in the range of $ 1.3 billion to 
$1.8 billion to bring one drug to market, it is clear that it would be 
impossible for NIH to compete with private industry.\13\ What NCATS 
intends to do is advance the science of therapeutic development and 
determine if there are ways we can re-engineer the drug development 
pipeline; creating new approaches and methods that will benefit 
everyone interested in speeding the delivery of new medicines.
---------------------------------------------------------------------------
    \13\ DiMasi, JA, Hansen RW, Grabowski HG. Extraordinary claims 
require extraordinary evidence. Journal of Health Economics 
2005;24(5):1034-1044. Tonkens, R. An Overview of the Drug Development 
Process. The Physician Executive May-June 2005.
---------------------------------------------------------------------------
    Today, the development of new diagnostics and therapeutics is a 
complex, costly, and risky endeavor. Only a few of the thousands of 
compounds that enter the drug development pipeline will ultimately make 
it into the medicine chest or to the patient's bedside. NCATS will 
study the various steps in the drug development pipeline, consult with 
the private sector to identify bottlenecks amenable to re-engineering, 
and experiment with innovative methods to streamline the process.
    To offer one example of the kind of pipeline challenge we might 
address, new ideas about assessing the toxic potential of drug 
candidates using sophisticated cell-based methods, instead of animal 
toxicology testing, hold out the promise of revolutionizing this step 
in validating a new therapeutic agent--and such research can be 
catalyzed by NIH in ways that might otherwise not be possible.
    NCATS will attack the bottlenecks in the drug development pipeline 
by experimenting with innovative approaches in an open-access model so 
that all stakeholders, ranging from industry to patients, will be able 
to access and apply its innovations. NCATS's open access operating 
framework will also advance the field of regulatory science by 
promoting interactions among the Food and Drug Administration (FDA), 
NIH, patient advocates, and pharmaceutical and biotechnology companies. 
NCATS will encourage collaboration across all sectors, provide 
resources to enable therapeutic development, and support and enhance 
training in the relevant translational science disciplines.
    NCATS will complement--not compete with--translational research 
being carried out elsewhere at NIH and in the private sector. In fact, 
in pursuing its mission of using the power of science to advance the 
entire discipline of translational science, NCATS will benefit all 
stakeholders, including academia, biotechnology firms, pharmaceutical 
companies, the FDA, and--most importantly--patients and their families.
    NCATS will pull together existing NIH programs such as the 
Therapeutics for Rare and Neglected Diseases program, the Office of 
Rare Diseases Research, the Rapid Access to Interventional Development 
program, the Clinical and Translational Science Awards, the FDA-NIH 
Regulatory Science grants program, and components of the Molecular 
Libraries initiative. These relocated programs will have their 
respective budgets transferred to or implemented by the new center. In 
addition, we are hopeful that funding for the new Cures Acceleration 
Network will be provided within the NCATS appropriation in fiscal year 
2012. The intent of this innovative program and its exceptional DARPA-
like flexibilities for supporting projects are a natural fit with 
NCATS.
    Aside from the new funding requested in fiscal year 2012 for the 
Cures Acceleration Network, resources for NCATS will come from the 
combination of already existing and appropriated programs and so be 
budget neutral.
    NCATS will bring the scientific method to bear on today's drug 
development process and aim to improve and speed the therapeutic 
development process of tomorrow.

                               CONCLUSION

    This statement has provided you with a brief overview of NIH's past 
successes and future commitment to basic and translational sciences, 
along with a quick look at the important role that NIH plays in our 
domestic economy and U.S. global economic and scientific leadership.
    But I would like to close my testimony today with an example that 
demonstrates the benefits to be reaped from our continuing pursuit of 
``personalized medicine.'' It is the story of one individual, 6-year-
old Nic Volker of Monona, Wisconsin. Starting about the age of 2, Nic 
developed a mysterious, life-threatening disease that ravaged his 
intestines, making it impossible for him to eat normally and causing 
unimaginable pain and suffering. At a loss to explain this terrible, 
inflammatory condition, researchers and clinicians at the Medical 
College of Wisconsin decided to sequence Nic's entire exome, that is, 
all the parts of the genome that code for the proteins that become 
life's building blocks. After exhaustive work over a period of months, 
the researchers identified a mutation in Nic's XIAP gene. Such 
mutations had been associated with rare blood disorders, but not with 
bowel symptoms. Based on this new insight, the research team had an 
idea that, as with the rare blood disorders, Nic's disease might be 
curable with a bone marrow transplant.
    NIH investment over the years in the sequencing of genomes--and the 
technologies associated with such sequencing--has put us at the 
threshold of ``personalized medicine.'' Young Nic Volker is one of a 
handful of individuals who has crossed that threshold, and it was made 
possible because of years of research and development supported and 
performed by NIH.
    Transplantation of cord-blood stem cells from a matched donor 
occurred in July of last year and, although Nic is still on 
immunosuppressant drugs to prevent rejection of the donated cells, his 
symptoms have largely disappeared and today he can eat normally. Hot 
dogs are his favorite!
    The local newspaper, the Milwaukee Journal Sentinel, was so struck 
by the saga of Nic and his family that they devoted a series of 
articles to the little boy's struggles and therapy, coverage that 
included posting photos, videos, blogs, and many other resources to the 
web. The five Journal Sentinel journalists did such a good job that 
they were awarded the Pulitzer Prize for Explanatory Reporting on April 
18. Now, that is truly putting a face on the promise of today's 
biomedical research, tomorrow's personalized medicine, and NIH's role 
in making this promise possible.
    Thank you Mr. Chairman. This concludes my formal remarks.
                                 ______
                                 
               Prepared Statement of Harold Varmus, M.D.

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National Cancer 
Institute (NCI) of the National Institutes of Health (NIH). The fiscal 
year 2012 request includes $5,196,136,000 for NCI, which reflects an 
increase of $141,899,000 over the comparable fiscal year 2011 level of 
$5,054,237,000.
    We now know that cancer is a collection of diseases reflecting 
changes in a cell's genetic makeup and thus its programmed behavior. 
Sometimes the genetic changes occur spontaneously or are inherited; 
sometimes they are caused by environmental triggers, such as chemicals 
in tobacco smoke, ultraviolet radiation from sunlight, or viruses. 
While cancers constitute an incredibly diverse and bewilderingly 
complex set of diseases, we have at hand the methods to identify 
essentially all of the genetic changes in a cell and to use that 
knowledge to rework the landscape of cancer research and cancer care, 
from basic science to prevention, diagnosis, and treatment. The funds 
in the President's budget for NCI represent a bold investment strategy 
critical for realizing that goal.
    The emerging scientific landscape offers the promise of significant 
advances for current and future cancer patients, and for preventing 
cancer so that many never become cancer patients. And it offers 
scientists at the National Cancer Institute--and in the thousands of 
laboratories across the United States that receive NCI support--the 
opportunity to increase the pace of lifesaving discoveries 
dramatically.
    In the past year alone, we have seen powerful examples of how 
research dollars have translated into concrete advances against cancer 
through basic science, prevention and early detection, and treatment.
    Basic science.--In collaboration with NHGRI, the NCI is leading The 
Cancer Genome Atlas (TCGA), the largest and most comprehensive analysis 
of the molecular basis of cancer ever undertaken. TCGA aims to identify 
and catalog all of the relevant genetic alterations in many types of 
cancer. For instance, building on their recent reclassification of 
glioblastoma multiforme (GBM), an aggressive form of brain cancer, this 
year TCGA investigators discovered that about 10 percent of patients 
with one of the four subtypes of GBM are younger at diagnosis and live 
longer than patients with other subtypes of the disease, but their 
tumors are unresponsive to current intensive therapies. The molecular 
profile of this subtype offers new targets for developing drugs to 
treat this form of the disease more effectively. TCGA scientists are 
also preparing to publish similarly important findings about the major 
form of ovarian cancer in mid-2011 and are in the midst of analyzing 
nearly 20 other types of cancer.
    Prevention and early detection.--NCI's intensive efforts to study 
and reduce the use of tobacco products have contributed to a sustained 
annual reduction in age-adjusted cancer mortality rates over the past 
decade and more. But current and former heavy smokers remain at high 
risk of developing lethal lung cancers, which are the leading cause of 
cancer mortality. In late 2010, NCI announced initial results from the 
National Lung Screening Trial, a large, multi-year randomized trial 
that enrolled more than 53,000 subjects. Because early detection 
provides the potential to intervene at the earliest, most treatable 
stages of disease, thus reducing potentially difficult to treat 
outcomes seen in more advanced disease, current and former smokers who 
were screened with low-dose helical computed tomography were 20 percent 
less likely to die of lung cancer than were peers who received standard 
chest x-rays. These results provide the first clear demonstration that 
a screening procedure can be effective in reducing mortality from lung 
cancer--a finding that could save many lives among those at greatest 
risk. Over the course of the $240 million study, NLST investigators 
collected samples of early and advanced lung cancers from enrolled 
subjects, and these specimens will be invaluable for determining 
genetic alterations that may be used to predict which tumors are likely 
to progress to an advanced stage.
    Cancer treatment.--The potential therapeutic impact of basic 
discoveries made by TCGA and other efforts in cancer genomics has been 
dramatically illustrated this year by the development of effective 
drugs against the most deadly form of skin cancer, melanoma. Almost a 
decade ago, studies of cancer genomes first uncovered a common mutation 
in a gene that encodes an enzyme called BRAF. Last year, early stage 
clinical trials at NCI-designated Cancer Centers of drugs targeted 
against the mutant BRAF enzyme showed that most melanomas with the 
relevant mutation regressed dramatically. Although tumor regression 
generally lasted less than a year, NCI-supported investigators have 
already pinpointed some causes of resistance to BRAF inhibitors, 
outlining a pathway to more sustained control of this lethal disease.
    Another benefit of a prolonged and broad-based investment in cancer 
research has also been realized in the context of malignant melanoma 
this year, with the recent approval by the FDA of an antibody, 
ipilimumab, which extends the lives of patients with metastatic 
melanoma. Ipilimumab stimulates the immune system to act against cancer 
by blocking natural inhibitors of the immune response, an approach that 
would not be possible without a profound understanding of the immune 
system and one that promises to harness immunological tools against 
other cancers.
    These examples of NCI's progress in understanding, treating, and 
detecting different forms of cancer illustrate what can be achieved at 
an accelerated pace with sustained investments across the cancer 
research spectrum, such as proposed under the President's budget. While 
those perspectives are only beginning to inform the American public's 
perception about cancer and its treatment, the downward trajectory of 
cancer deaths--reported by NCI and its partners in March--reflects real 
and sustained reductions over more than a decade for numerous cancers, 
including the four most common: breast, colorectal, lung, and prostate. 
We have identified proteins and pathways that different cancers may 
have in common and represent targets for new drugs for these and many 
other cancers--since so often research in one cancer creates potential 
benefits across others.
    Additional progress against cancer also will require building these 
research advances into clinical treatments and diagnostic tools for 
better patient care and by our many connections with public and private 
sector partners. The Institute's investments in translational research 
are broad and deep, and will receive NCI's full energies, recognizing 
that the publicly announced proposal for reorganizing services that 
support translational science in general could give NIH additional 
focus in this important area.

             REVITALIZING THE CANCER CLINICAL TRIALS SYSTEM

    For today's new understandings of cancer biology to benefit cancer 
patients on a broad scale, they must be coupled with a modernized 
system for conducting cancer clinical trials. This system must enable 
clinical researchers across the Nation to acquire tumor specimens and 
conduct genetic tests on each patient, to efficiently analyze molecular 
changes in those samples, to manage and secure vast quantities of 
genetic and clinical data, and to identify subsets of patients with 
tumors that demonstrate changes in specific molecular pathways--
pathways that can be targeted by a new generation of cancer therapies.
    As part of its effort to transform the cancer clinical trials 
system, NCI asked the Institute of Medicine (IOM) in 2009 to review the 
Clinical Trials Cooperative Group Program. This program involves a 
national network of 14,000 investigators currently organized into nine 
U.S. adult Cooperative Groups and one pediatric cooperative group that 
conduct large-scale cancer clinical trials at 3,100 sites across the 
United States. The IOM report, issued in April 2010, noted that the 
current trials system--established a half-century ago--is inefficient, 
cumbersome, underfunded, and overly complex. Among a series of 
recommendations, the report urged that the existing adult cooperative 
groups be consolidated into a smaller number of groups, each with 
greater individual capabilities and with new means to function with the 
others in a more integrated manner.
    In December 2010, NCI announced its intent to begin consolidating 
the current nine adult cooperative groups into four state-of-the-art 
entities that will design and perform improved trials of cancer 
treatments, as well as explore methods of cancer prevention and early 
detection, enhance the ability of the cooperative groups to assess the 
molecular characteristics of individual patients' tumors, and study 
quality-of-life issues and rehabilitation during and after treatment. 
The sole pediatric cooperative group was created by consolidating four 
pediatric cooperative groups almost a decade ago, and that group will 
not be affected by the current consolidation effort.

                         PROVOCATIVE QUESTIONS

    This has been a challenging and hopeful time for NCI to lead the 
Nation's cancer research program. Over the past two decades researchers 
have unraveled some of the damage that occurs in the genome of a cancer 
cell and how a cancer cell behaves in its local environment as a result 
of those changes. With this better understanding of cancer and recent 
technological advances in many fields, such as genomics, molecular 
biology, biochemistry, and computational sciences, progress has been 
made on many fronts, and a portrait has emerged for several cancers. 
With sustained and accelerated funding, and NCI's strong leadership in 
defining cancer research priorities, we can build upon today's cancer 
advances with provocative thinking by asking better questions.
    To that end, NCI is asking researchers in various disciplines to 
pose and articulate ``provocative questions'' that can help guide the 
Nation's investment in cancer. Provocative questions may be built on 
older, neglected observations that have never been adequately explored, 
or on recent findings that are perplexing, or on problems that were 
traditionally thought to be intractable but now might be vulnerable to 
attack with new methods.
    Many of these provocative questions are being asked--and answered--
by young scientists who are early in their careers. The 2012 budget 
will support NCI's commitment to ensuring that an equitable share of 
our research grants will go to the young men and women, who are at the 
forefront of understanding cancer.
    We are now reaping the rewards of investments in cancer research 
made over the past 40 years or more, even as we stake out an investment 
strategy to realize the potential we see so clearly for the future. The 
public has benefitted from past generous congressional stewardship of 
biomedical research funding; cancer research over the past four decades 
has provided the evidence required to lower the incidence and mortality 
of many kinds of cancer, to improve the care of cancer patients, and to 
establish the new understanding of cancer that is now beginning to 
revolutionize control of cancer throughout the world.
    No matter what the fiscal climate, NCI will strive to commit the 
resources necessary to bring about a new era of cancer research, 
diagnosis, prevention, treatment, and survivorship.
    Thank you for the opportunity to provide you this testimony, and I 
would be pleased to answer any questions you might have.
                                 ______
                                 
              Prepared Statement of Susan B. Shurin, M.D.

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Heart, Lung, and Blood 
Institute (NHLBI) of the National Institutes of Health (NIH). The 
fiscal year 2012 budget of $3,147,992,000 includes an increase of 
$80,903,000 over the comparable fiscal year 2011 level of 
$3,067,089,000.
    The NHLBI provides global leadership for a research and education 
program to promote prevention and treatment of heart, lung, and blood 
diseases. Our vision is to enhance the health of all individuals and 
thereby enable them to enjoy longer and more productive lives. The 
Institute advances its objectives through an innovative program of 
excellent science that addresses urgent public health needs, 
capitalizes upon extraordinary opportunities, leverages strategic 
assets, balances and integrates basic and clinical research approaches, 
and calls upon the creativity, expertise, and dedication of thousands 
of scientists here and abroad. The American people have generously 
supported this work for many years, and tremendous progress has 
resulted.
    This testimony highlights three areas of particular current 
emphasis: (1) genetics and genomics; (2) regenerative medicine; and (3) 
translational medicine.

                         GENETICS AND GENOMICS

    NHLBI-funded gene-sequencing projects and genome-wide association 
studies have been extraordinarily productive. Scanning the genomes of 
more than 100,000 people from all over the world, scientists recently 
reported the largest set of genes yet discovered that underlie blood 
lipid variations known to be major risk factors for coronary heart 
disease. Altogether, the gene variants explain between one-quarter and 
one-third of the inherited portions of cholesterol and triglyceride 
measured in the blood. Of the variants, 59 had not been previously 
identified and thus provide new clues for developing effective 
medicines to combat heart disease. This exciting discovery follows upon 
similar research, reported in 2009, regarding another heart disease 
risk factor--hypertension. Using genomic analysis of over 29,000 
participants from the Framingham Heart Study and other cohorts, an 
international research team identified a number of unsuspected genetic 
variants associated with systolic and diastolic blood pressure. 
Although hypertension has long been known to run in families and have a 
substantial genetic component, previous attempts to identify genes 
associated with blood pressure had met with only limited success. The 
new findings from both the lipid and the blood pressure studies 
illustrate the potential of large-scale genome-wide scans to identify 
genes that play roles in a complex disease of widespread public health 
importance.
    Smaller-scale genome-wide scans are also providing valuable new 
information about less common disorders, such as thoracic aortic 
aneurysm and dissection--a condition that is often asymptomatic until 
an unpredictable catastrophic cardiovascular event occurs. Researchers 
comparing 418 patients with non-familial thoracic aneurysms to normal 
controls identified a number of genetic variants that appeared more 
frequently in the patients. Many of the variants exist in genes that 
are in some manner involved in contraction of smooth-muscle cells, 
suggesting that genetic variants governing smooth-muscle cell function 
are a potential target of predictive tests that could be developed in 
the future.
    Although genome-wide scans and sequencing have identified many 
genetic variations that contribute to disease risk, much more research 
is needed to understand the mechanisms underlying gene disease 
associations. NHLBI is advancing this area by supporting a new program, 
Next Generation Genetic Association Studies, to investigate cells that 
have been reprogrammed into induced pluripotent stem cells to model 
heart, lung, and blood diseases and explore the functional consequences 
of genetic variation.
    Another initiative, Getting from Genes to Function in Lung Disease, 
will support characterization of the function of lung-disease 
associated genes and their variants that have been identified through 
GWAS or other genetic approaches. Multidisciplinary teams will use a 
variety of experimental methods and tools to elucidate the mechanisms 
that contribute to diseases such as asthma, chronic obstructive 
pulmonary disease (COPD), sarcoidosis, and idiopathic pulmonary 
fibrosis and thereby generate knowledge that may lead to more effective 
ways to prevent and treat them. In fiscal year 2012, the Institute 
plans to solicit research projects to study two severe and poorly 
understood conditions that affect the lungs: The Genomic Research in 
Alpha-1 Antitrypsin Deficiency and Sarcoidosis program will conduct 
state-of-the-art genomic, microbiomic, and phenotypic studies with the 
goals of understanding the molecular and cellular bases of the 
diseases, facilitating classification of sub-types, and developing new 
drug therapies.
    Because genome-wide scans are not well suited to discovery of 
extremely uncommon genetic variants, the Institute is pursuing other 
avenues to explore the contributions of infrequent variants to both 
common and rare diseases. A program planned for fiscal year 2012 in 
collaboration with the National Human Genome Research Institute, Life 
After Linkage: The Future of Family Studies, will use data from 
existing family studies to identify and characterize genes, including 
rare variants, that influence complex diseases. The potential success 
of such an approach is illustrated by a recent breakthrough resulting 
from a collaboration between the NHLBI intramural program and the NIH 
Undiagnosed Diseases Program. Researchers identified the genetic cause 
of a rare and debilitating vascular disorder, not previously explained 
in the medical literature, that involves severe arterial calcification. 
Analysis of DNA from members of three affected families revealed that 
the variant is in a gene responsible for a product that protects 
arteries from calcifying. It is hoped that this understanding of the 
underlying defect will enable discovery of improved treatment for the 
patients.

                         REGENERATIVE MEDICINE

    Body components can malfunction because of inherent defects, 
catastrophic or accumulated damage, or senescence, and chronic disease 
is often the result. Restoring healthy function via delivery of 
``replacement parts'' and helping organs repair injury with functional 
tissue instead of scarring are high priorities of NHLBI. Recent 
progress gives much reason for optimism. For example, heart attacks 
cause permanent damage to heart muscle cells (cardiomyocytes) that 
renders them useless for pumping blood. Although cardiomyocytes cannot 
themselves be rejuvenated, NHLBI-supported scientists were able to 
induce other heart cells (fibroblasts) to become pluripotent stem cells 
that, in turn, were induced to become cells that looked and behaved 
much like cardiomyocytes. The finding suggests the possibility that 
fibroblasts--cells widely available throughout the body--could be 
directly reprogrammed into functional cells to treat or prevent heart 
failure and other adverse consequences of cell damage. Other NHLBI-
supported researchers recently reported progress toward engineering 
lung tissue in a rat model, creating a scaffold populated with 
multipotent neonatal rat cells to produce a transplantable organ 
capable performing the fundamental lung function of gas exchange. The 
success of this study and others using cadaveric human lung tissue and 
immortalized cell lines suggests that such an approach might one day be 
beneficial for patients who are awaiting lung transplant.
    NHLBI is making considerable investments to advance regenerative 
medicine research for cardiovascular, lung, and blood diseases. A 
collaborative solicitation with the National Institute of Biomedical 
Imaging and Bioengineering, New Strategies for Growing 3D Tissues, will 
support highly integrated, multidisciplinary research to improve 
understanding of how cells respond to their environment and how cell-
communication systems that enable blood-vessel and organ development 
can be used to engineer 3D human cellular aggregates. Translation of 
Pluripotent Stem Cell Therapy for Blood Diseases will promote the 
development of technologies for translation of recent stem cell 
advances into treatments for sickle cell disease and other blood 
disorders. This new program will build upon the expertise, resources, 
and infrastructure of the ongoing NHLBI Progenitor Cell Biology 
Consortium, and it will encourage collaboration with two other 
Institute initiatives--Production Assistance for Cellular Therapies and 
the Gene Therapy Resource Program, which is slated for renewal in 
fiscal year 2012.
    A major initiative planned for fiscal year 2012, Consortium of Lung 
Repair and Regeneration: Building the Foundation, will establish an 
interactive group of multidisciplinary teams to formulate and test 
innovative hypotheses about the mechanisms that control lung repair and 
regeneration. The program will seek to leverage innovative technologies 
such as tissue engineering, biomaterials and scaffolds, induced 
pluripotent stem-cell technology, cell-directed therapy, and humanized 
animal models that are not used widely in lung-regeneration research 
but are being applied to investigate regeneration and repair in other 
organ systems.

                         TRANSLATIONAL MEDICINE

    NHLBI continues to place strong emphasis on translating basic 
science findings into better diagnostic, therapeutic, and preventive 
approaches and fostering their use in real-world clinical practice. A 
number of initiatives are supporting these efforts. For example, a 
program called Science Moving Towards Research Translation and Therapy 
(SMARTT) has been launched to facilitate transition of potential new 
therapies for heart, lung, and blood diseases from discovery in the lab 
to the testing needed to establish their safety and effectiveness in 
people. Pre-clinical development--that is, readying products for 
testing in humans--is the first step in turning discoveries into cures, 
but the processes involved can be expensive and baffling to academic 
scientists. Connecting academic researchers with industry, the SMARTT 
program will offer help with manufacturing, pharmacology and toxicology 
testing, pre-clinical and early-phase clinical study design, and 
administrative and regulatory matters.
    The Translational Research Implementation Program, or TRIP, is 
intended to facilitate well-designed clinical trials in heart, lung, or 
blood diseases to demonstrate the safety and efficacy of promising 
interventions that have emerged from fundamental studies. Its initial 
phase, which began in fiscal year 2010, supported the planning of 
trials; the second phase will fund the most promising of them beginning 
in fiscal year 2012. A second new program will provide planning grants 
to establish the feasibility of pivotal clinical trials with a major 
focus on hemoglobinopathies such as sickle cell disease and 
thalassemia. Another solicitation, planned for fiscal year 2012, would 
provide an innovative mechanism for the development of clinical trials 
for hemostatic and thrombotic disorders, including access to expertise 
in clinical trial methodology and design through existing institutional 
resources.
    Several exceptionally promising new translational efforts in lung 
diseases are also under way. Research Education in Sleep and Circadian 
Biology is promoting the use of innovative educational tools and 
programs to accelerate the transfer of recent scientific advances and 
health knowledge in sleep and circadian biology into clinical and 
public-health practice. Renewal of a solicitation titled Utilization of 
a Human Lung Tissue Resource for Vascular Research will advance 
translational efforts in lung vascular disease, using previously 
collected biospecimens from patients with pulmonary hypertension. An 
initiative slated for fiscal year 2012 would support dosing and 
efficacy trials of promising but untested therapies for lung diseases, 
including agents that have already been approved for use in treating 
other diseases and combinations of common drugs with low toxicities, 
neither of which would be likely candidates for testing by industry. 
Such small proof-of-concept trials are vitally important for 
translating basic research advances into clinical research, providing a 
foundation for larger efficacy trials, and advancing understanding of 
disease processes.
                                 ______
                                 
        Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P.

    I am pleased to present the President's fiscal year 2012 budget 
request for the National Institute of Diabetes and Digestive and Kidney 
Diseases (NIDDK) of the National Institutes of Health (NIH). The fiscal 
year 2012 budget includes $1,837,957,000, which is $47,272,000 more 
than the comparable fiscal year 2011 level. Complementing these funds 
is an additional $150,000,000 also available in fiscal year 2012 from 
the Special Statutory Funding Program for Type 1 Diabetes Research. The 
NIDDK supports research on a wide range of common, chronic, costly, and 
consequential diseases and 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 disorders.

 UNCOVERING THE GENETIC AND ENVIRONMENTAL CAUSES OF DISEASE TO INFORM 
                         THERAPY AND PREVENTION

    Unprecedented discoveries in genetics continue to lead the way 
toward the development of personalized treatments and prevention of 
devastating diseases and disorders. Scientists revealed that certain 
variants in the APOL1 gene may be responsible for the differential risk 
of developing kidney disease for African Americans. These variants also 
provide a degree of protection against African sleeping sickness, a 
degenerative and potentially fatal condition caused by a parasite that 
is endemic to Africa. This could explain why these variants are more 
commonly found in individuals of African descent, despite the increased 
risk of kidney disease they confer.
    Many of the diseases within the NIDDK research mission result from 
the interaction between multiple genetic and environmental factors. 
Research on the human microbiome--the microorganisms associated with 
the body--has demonstrated that the composition of bacterial 
communities is determined mostly by their location on or in the body 
and varied between people. In a separate study, scientists reported 
that bacteria in the mouse gut contributed to changes in appetite and 
metabolism. Therefore, excess calorie composition and obesity may be 
affected by these bacterial populations. Researchers in The 
Environmental Determinants of Diabetes in Youth are using newly 
developed technologies to study the microbiome of children at high risk 
for developing type 1 diabetes and explore whether viral or bacterial-
based treatments could be used to prevent or treat the disease. NIDDK 
will continue to capitalize on recent genetics and environment 
discoveries to transform prediction, prevention, diagnosis, and 
treatment of diseases within the Institute's mission.

                IMPROVING PATIENT CARE THROUGH RESEARCH

    Obesity is a major health epidemic in the United States, and it 
increases the risk for type 2 diabetes; kidney, heart, and liver 
disease; and other health issues. Therefore, efforts to curb this 
rising trend are vitally important. The NIDDK's HEALTHY study revealed 
that while a middle school-based intervention did not reduce obesity 
school-wide, it lowered the obesity rate in students with the highest 
risk for type 2 diabetes. This important result will inform future 
school-based efforts to reduce overweight and obesity in children. 
Research also shows that weight loss can improve the health of people 
with diabetes. NIDDK's Look AHEAD study showed that weight loss in 
overweight and obese people with type 2 diabetes can lead, with lower 
medication requirements, to long-term favorable effects on diabetes 
control and cardiovascular risk factors.
    NIDDK continues to support efforts to test potential treatments for 
NIDDK-related diseases and disorders. Investigators demonstrated in a 
preliminary trial that salsalate, an anti-inflammatory drug used for 
years to manage arthritis pain, can help people with type 2 diabetes 
control blood glucose levels. If the expanded trial is successful, it 
could lead to a safe and inexpensive way to treat the disease. Non-
alcoholic steatohepatitis (NASH) is a form of fatty liver disease 
associated with overweight and can lead to liver cirrhosis and liver 
failure requiring a transplant. Currently, there are no specific, FDA-
approved treatments for NASH. NIDDK scientists compared vitamin E, the 
insulin-sensitizing drug pioglitazone, and placebo for treatment of 
adult NASH, and reported promising improvements in response to 2-year 
therapy, especially for vitamin E.
    It is important to compare available, effective treatments and 
combine this knowledge with a patient's history to identify the best 
option for treating an individual. A recent NIDDK study demonstrated 
that, on average, a lower blood pressure goal was no better than the 
standard goal at slowing progression of kidney disease among African 
Americans who had chronic kidney disease resulting from high blood 
pressure. However, the lower blood pressure goal did benefit patients 
who had protein in their urine, a sign of kidney damage. In light of 
the APOL1 results I described earlier, this and other findings suggest 
that genetic traits more common in African Americans may subtly alter 
the pathogenesis of kidney disease in this population, and new classes 
of drugs that target these pathways might be more effective in 
preventing the onset and progression of chronic kidney disease in these 
patients.
    Millions of American women suffer from stress urinary incontinence, 
an underdiagnosed public health problem that is associated with 
diminished quality of life. An NIDDK trial demonstrated that two 
different surgical approaches were equally effective--although they had 
different side effects--in treatment for stress urinary incontinence, a 
major milestone in treatment for this condition. This information will 
enable women and their doctors to weigh more accurately the benefits 
and risks of available treatment options. In concert with identifying 
the best treatment options, NIDDK research aims to ensure that patients 
are able to take advantage of these results to improve their health and 
care.

        DISSEMINATING RESEARCH RESULTS TO IMPROVE PUBLIC HEALTH

    It is critical that the results of research reach the American 
public quickly and clearly to translate to real improvements in health. 
NIDDK supports a number of public health campaigns such as the National 
Kidney Disease Education Program, the Weight-control Information 
Network, a Celiac Disease Awareness Campaign, and the National Diabetes 
Education Program (NDEP).
    Diabetes continues to be a growing worldwide public health concern; 
rising rates of obesity and an aging populance are driving the 
increasing prevalence of type 2 diabetes. There is hope, however: 
research has shown that it is possible to delay--or even prevent--the 
disease. The NIDDK's landmark Diabetes Prevention Program (DPP) was a 
tremendous success, demonstrating that loss of 5-7 percent of an 
individual's body weight--or treatment with the drug metformin--can 
delay type 2 diabetes. By eating less fat and fewer calories and doing 
moderate exercise, such as brisk walking, DPP participants were able to 
lose body weight and maintain the loss. These lifestyle changes worked 
particularly well for participants age 60 and older, and were equally 
effective for all participating ethnic groups and for both men and 
women.
    To transfer the lessons of the DPP to the community level, NIDDK 
supports translational research, which included a trial of less costly 
delivery of the DPP intervention in YMCAs in group settings. The 
results have led CDC and private organizations to fund the intervention 
at more Ys and United Health Group to cover the cost for plan 
participants to use the intervention at Ys. Additionally, the NDEP is 
disseminating the good news from the DPP follow-up study that 
development of type 2 diabetes continued to be reduced 10 years after 
the intensive lifestyle change or treatment with metformin. NDEP has 
partnered with NIH's Office of Research on Women's Health to also raise 
awareness of the increased risk of type 2 diabetes for women who have a 
history of gestational diabetes.

                   GENERATING RESEARCH OPPORTUNITIES

    The future of public health depends critically on the development 
of the next generation of scientists and the pursuit of scientific 
opportunities. NIDDK continues to vigorously support new investigators, 
and training and mentorship in biomedical research. NIDDK held its 
second annual New Investigators' meeting to enhance their ongoing 
research and spur future success. NIDDK also held its eighth annual 
workshop for the Network of Minority Research Investigators to 
encourage and facilitate participation of members of underrepresented 
racial and ethnic minority groups in the conduct of biomedical research 
in NIDDK-relevant fields. These new investigators will be poised to 
take advantage of a wealth of opportunities to improve the health of 
Americans; such opportunities have been identified by a number of 
recent strategic planning efforts undertaken by the NIDDK.
    The development and application of new technologies will also 
improve patient care. Through support for small business innovation 
research grants and other efforts, NIDDK will foster cutting-edge 
research in this area. New technologies could facilitate analysis of 
organs, tissues and biological molecules, and, with mobile 
communication, help convey critical information quickly to patients and 
healthcare providers. This research would enhance our ability to 
monitor disease progression or how a therapy is working and would 
improve diagnosis of disease or risk, to enable earlier intervention.
    In closing, Mr. Chairman, NIDDK will continue to emphasize my 
guiding principles: support a robust portfolio of investigator-
initiated research; vigorously support clinical trials to identify 
better ways to prevent and treat disease; preserve a stable pool of new 
investigators; disseminate science-based knowledge from research 
through education programs; and foster research training and mentoring.
    Thank you Mr. Chairman and members of the Committee for the 
opportunity to share with you a few highlights of NIDDK's research and 
outreach efforts to improve the health of Americans. I will be pleased 
to answer any questions you may have.
                                 ______
                                 
              Prepared Statement of Anthony S. Fauci, M.D.

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Institute of Allergy and Infectious Diseases (NIAID), a component of 
the National Institutes of Health (NIH). The fiscal year 2012 budget 
includes $4,915,970,000, which is $144,100,000 more than the comparable 
fiscal year 2011 level of $4,771,870,000.
    NIAID conducts and supports biomedical research to understand, 
treat, and prevent infectious and immune-mediated diseases, including 
HIV/AIDS; tuberculosis; malaria; influenza; emerging and re-emerging 
infectious diseases; asthma and allergies; autoimmune diseases; and the 
rejection of transplanted organs. NIAID makes a major investment in 
translational research, which seeks to accelerate the findings from 
basic research into healthcare practice. This decades-long commitment, 
together with NIAID's multidisciplinary collaborations with experienced 
as well as new investigators at academic centers, the private sector, 
and other governmental and non-governmental partners, continues to help 
improve domestic and global health through the development of 
diagnostics, therapeutics, and vaccines for infectious and immune-
mediated diseases. I appreciate the opportunity to highlight just a few 
of our research successes and to describe some of our most promising 
research programs aimed at improving public health and quality of life.

                             GLOBAL HEALTH

    NIAID has been a leader in both basic and clinical HIV/AIDS 
research ever since the disease emerged as a devastating public health 
crisis 30 years ago. In 2010, NIAID support for HIV/AIDS research 
resulted in landmark scientific advances in HIV prevention. The NIAID-
supported iPrEx study demonstrated that a daily dose of an oral 
antiretroviral medication, a strategy known as pre-exposure prophylaxis 
or PrEP, was effective at reducing the risk of HIV acquisition among 
men who have sex with men. This finding was selected by the prestigious 
journal The Lancet as one of the top six medical discoveries in the 
world in 2010 and was named by Time magazine as the number one medical 
breakthrough in 2010. A second important study, and another of The 
Lancet's selections, CAPRISA 004, showed that a vaginal microbicide gel 
of an antiretroviral drug could give women a measure of protection 
against HIV infection. This important trial was funded by the U.S. 
Agency for International Development and carried out using a research 
infrastructure developed with NIAID support. In the area of HIV vaccine 
development, researchers in NIAID's intramural Vaccine Research Center 
and NIAID-funded extramural investigators discovered human antibodies 
that can block a wide range of HIV strains from infecting human cells 
in the laboratory and are now zeroing in on their precise mechanisms of 
action. Coupled with last year's success from the RV 144 HIV vaccine 
clinical trial conducted in Thailand, which found a ``prime-boost'' 
vaccine candidate to be safe and modestly effective in preventing HIV 
infection, NIAID is making important strides in developing a robust 
package of prevention modalities that can be used in combination. In 
addition, research supported under NIAID's new initiative, the Martin 
Delaney Collaboratory: Towards an HIV Cure, will provide insights into 
how HIV hiding places in the body--so-called ``reservoirs''--are 
formed, where they are located, how they are maintained despite 
effective antiretroviral therapy, and how they might be eliminated.
    NIAID makes a significant investment in research on the co-
infections and co-morbidities that often accompany HIV infection. 
Tuberculosis (TB) occurs in about one-third of HIV-infected individuals 
and is the leading cause of death in this group. The NIAID-sponsored 
CAMELIA study demonstrated that survival of untreated HIV-infected 
adults with weak immune systems and newly diagnosed TB can be prolonged 
by starting antiretroviral therapy 2 weeks after beginning TB 
treatment, rather than waiting the standard 8 weeks. This finding will 
help to optimize treatment strategies for people co-infected with HIV 
and TB and promises to save many lives in the developing world. A 
significant number of adults at risk for HIV infection are also at risk 
for hepatitis B and C infection. NIAID supports a robust research 
program to understand the pathogenesis of and immune response to 
hepatitis viruses and to develop novel therapeutics and vaccines 
against the diseases caused by these viruses.
    In 2009, there were approximately 9.4 million TB cases and 1.7 
million TB deaths globally according to the World Health Organization 
(WHO). NIAID has accelerated its TB research activities and is applying 
21st century technology to a field that has lagged behind the study of 
other infectious diseases. NIAID supports the development of several 
promising TB vaccine candidates, and basic and clinical research has 
contributed to both new and repurposed therapeutic approaches and 
candidates. With NIAID support, researchers also have developed a tool 
for diagnosing TB that provides more specific, sensitive, and rapid 
results than currently available diagnostics.
    In 2009, approximately 225 million cases of malaria resulted in 
more than 780,000 deaths, 90 percent of which occurred in Africa, 
according to WHO. More than a decade has passed since the newest class 
of antimalarial drugs, artemisinins, entered widespread use worldwide; 
unfortunately, malaria parasites are becoming increasingly resistant to 
these medications. There is a pressing need for new malaria therapies 
due to the constant threat of the emergence of drug resistance, which 
NIAID is addressing by supporting domestic and international research. 
For example, NIAID-supported researchers identified NITD609 as a 
promising antimalarial drug with a mode of action that differs from the 
current drugs used to treat malaria. NIAID-supported scientists also 
discovered a novel metabolic pathway of the malaria parasite Plasmodium 
falciparum that could lead to new drug targets. In 2010, NIAID 
established ten International Centers of Excellence for Malaria 
Research in malaria-endemic regions. In addition to research on HIV/
AIDS, TB, and malaria, NIAID supports research devoted to better 
understanding, preventing, and treating other important diseases that 
cause a significant burden of illness and death globally, including 
neglected tropical diseases such as lymphatic filariasis, trachoma, and 
leishmaniasis.

              EMERGING AND RE-EMERGING INFECTIOUS DISEASES

    NIAID continues its critical focus on advancing drugs, vaccines, 
and diagnostics from concept to product development to fight emerging 
and re-emerging infectious diseases. In response to the 2009 H1N1 
influenza pandemic, NIAID played a key role in developing and testing 
the 2009 H1N1 influenza vaccines, and in assessing their safety and 
potential effectiveness in a variety of populations. NIAID researchers 
also made important strides in the development of broadly protective 
influenza vaccines. NIH intramural researchers in the Vaccine Research 
Center demonstrated that a ``prime-boost'' vaccine strategy could 
protect animals from infection with multiple strains of influenza. 
NIAID-supported scientists also determined that individuals infected 
with pandemic 2009 H1N1 influenza generated antibodies that neutralized 
many different influenza virus strains. This adds to the evidence base 
that a universal influenza vaccine may be possible, which would obviate 
the need to modify the influenza vaccine each season. NIAID-supported 
investigators also showed that vaccinating children against influenza 
protects the wider community, underscoring the public health importance 
of widespread vaccination with current and improved vaccines. The 
Lancet chose this study as its top scientific advance of 2010.
    Building on the experience and challenges of the 2009 H1N1 
influenza pandemic, the Department of Health and Human Services 
conducted a review of the Federal Government's efforts to develop 
medical countermeasures (MCMs) such as drugs and vaccines for public 
health emergencies, including bioterror attacks, culminating in a new 
vision for MCM development. As part of this vision, NIAID--in 
coordination with the Biomedical Advanced Research and Development 
Authority and the Department of Defense--will lead the Concept 
Acceleration Program to stimulate the translation of new scientific 
concepts and discoveries to the development of MCMs for biodefense and 
emerging infectious diseases.
    The dengue epidemic in Puerto Rico and dengue cases in Florida and 
Hawaii, as well as the cholera outbreak in earthquake-ravaged Haiti, 
demonstrate the importance of understanding the factors that contribute 
to disease emergence and re-emergence. NIAID dengue research includes 
basic research, vector biology, translational research, as well as the 
development of research tools, resources, and services. With NIAID 
support, scientists are developing several vaccine approaches for 
dengue. NIAID research on cholera spans basic research, genomics, 
studies of environmental and climactic factors, and the development of 
vaccines and therapeutics. An NIAID-supported study pinpointed the 
genetic lineage of the cholera microbe that is causing the epidemic in 
Haiti.
    NIAID continues to support a robust basic, translational, and 
clinical research portfolio to address the public health issue of 
antibiotic resistance for key pathogens, including methicillin-
resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria. For 
example, NIAID scientists recently identified a toxin from a community-
acquired strain of MRSA that could be a factor in the severity of MRSA 
infections. NIAID also supports research to preserve the effectiveness 
of currently used antibiotics, including studies to examine optimal 
treatment of community-acquired pneumonia and infections caused by 
Gram-negative bacteria such as Pseudomonas and Acinetobacter. NIAID-
supported researchers settled a medical controversy by recently showing 
that antibiotics clearly reduce the severity and duration of acute 
middle-ear infections in toddlers that were diagnosed using consistent 
criteria.

                       IMMUNE-MEDIATED DISORDERS

    NIAID is committed to furthering our understanding of the 
immunologic mechanisms underlying autoimmune diseases, asthma and 
allergic diseases, rejection of transplanted organs, and other immune-
mediated disorders; and to translating this knowledge into new 
approaches for diagnosis, prevention, and treatment. In 2010, an NIAID-
sponsored expert panel produced much-needed comprehensive guidelines 
for medical practitioners for the diagnosis and management of food 
allergy that will be helpful to clinicians across a range of medical 
specialties. NIAID also launched the Human Immunology Project 
Consortium to better understand the human immune system and how it 
reacts to infection or vaccination. The information gained from this 
effort will provide insights into the development of safer and more 
effective vaccines, including those for young children and the elderly. 
In addition, researchers in the NIAID Immune Tolerance Network 
demonstrated that Rituxan is a safe and effective therapy for two 
forms of severe vasculitis, a rare and devastating disease of the blood 
vessels. These data were instrumental in the recent Food and Drug 
Administration-approval of Rituxan for this indication, representing 
the first licensed treatment for this disorder in 40 years. Also, the 
NIAID Inner-City Asthma Consortium determined that the addition of 
Xolair to NIH guidelines-based asthma therapy for young children and 
adolescents resulted in fewer asthma symptoms and severe asthma 
attacks.

                               CONCLUSION

    For more than 60 years, NIAID has conducted and supported basic and 
clinical research on infectious and immune-mediated diseases leading to 
the development of vaccines, therapeutics, and diagnostics that have 
significantly improved the health and saved the lives of millions 
around the world. NIAID will continue to support the highest quality 
research with the aim of translating fundamental discoveries into 
improved public health.
                                 ______
                                 
  Prepared Statement of Josephine P. Briggs, M.D., Director, National 
           Center for Complementary and Alternative Medicine

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National Center 
for Complementary and Alternative Medicine (NCCAM) of the National 
Institutes of Health. The fiscal year 2012 budget includes 
$131,002,000, which is $3,399,000 more than the comparable fiscal year 
2011 appropriation of $127,603,000.
    The National Center for Complementary and Alternative Medicine 
(NCCAM) is the Federal Government's lead agency for scientific research 
on complementary and alternative medicine (CAM). CAM includes a group 
of diverse medical and healthcare interventions, practices, products, 
or disciplines that are not generally considered part of conventional 
medicine (sometimes called Western or allopathic medicine). The 
boundaries between CAM and conventional medicine are not absolute; 
instead, they are constantly evolving: interventions such as hospice 
care or relaxation and breathing techniques in childbirth that were 
once considered unconventional are now widely accepted. Furthermore, 
there is growing interest in more integrative approaches that use both 
CAM and conventional interventions. For example, both the Departments 
of Defense \1\ and Veterans Affairs are integrating select CAM 
modalities into treatments for pain, stress, and sleep disorders.
---------------------------------------------------------------------------
    \1\ Pain Management Task Force Final Report: Providing a 
Standardized DOD and VHA Vision and Approach to Pain Management to 
Optimize the Care for Warriors and Their Families, Office of the Army 
Surgeon General, Department of Defense, May 2010.
---------------------------------------------------------------------------
    CAM is used by many in the United States, both in treating health 
problems and in promoting better health and well-being. Data from the 
2007 National Health Interview Survey \2\ (NHIS), developed under NCCAM 
leadership in collaboration with the National Center for Health 
Statistics at the Centers for Disease Control and Prevention (CDC), 
show that nearly 40 percent of adult Americans and 12 percent of 
children are using some form of CAM. The data also show that in 2007 
out-of-pocket expenditures for CAM totaled $33.9 billion. While this 
amount accounted for only 1.5 percent of total healthcare expenditures, 
it was more than 11 percent of out-of-pocket expenditures. Finally, 
NHIS data indicate that a large portion of CAM use is best described as 
``self-care'' in that it occurs outside of the framework of a 
relationship with a healthcare professional. The scope, associated 
costs, and self-care nature of CAM use in the United States reinforce 
the need to develop reliable, objective scientific evidence concerning 
the usefulness and safety--or lack thereof--of CAM interventions, and 
to ensure the public has access to accurate and timely evidence-based 
information.
---------------------------------------------------------------------------
    \2\ Nahin RL, Barnes PM, Stussman BA, et al. Costs of complementary 
and alternative medicine (CAM) and frequency of visits to CAM 
practitioners: United States, 2007. CDC National Health Statistics 
Report #18. 2009.
---------------------------------------------------------------------------
    NCCAM is shaping its research directions through our third 
strategic plan, which was developed with considerable input from our 
diverse stakeholder community and released in February 2011. The 
strategic plan, Exploring the Science of Complementary and Alternative 
Medicine (available at www.nccam.nih.gov), was built around three long-
range goals aimed at improving the state and use of scientific evidence 
regarding the two major reasons for use of CAM in the United States--
treating health problems and supporting or promoting better health and 
well-being. The three goals are to (1) advance the science and practice 
of symptom management; (2) develop effective, practical, personalized 
strategies for promoting health and well-being; and (3) enable better 
evidence-based decisionmaking regarding CAM use and its integration 
into healthcare and health promotion.

                       PAIN AND SYMPTOM MANGEMENT

    CAM approaches, as treatments for health problems, are used most 
often to manage symptoms such back or neck pain, arthritic or other 
musculoskeletal pain, headache, and insomnia. These are all difficult 
problems and there is broad agreement that existing options are less 
than fully satisfactory for many patients. For example, chronic back 
pain is, by far, the most frequent health problem for which Americans 
turn to CAM. They might try CAM approaches after exhausting other 
options such as opioids, injections, surgery, or physical therapy. More 
often, however, they pursue CAM treatment options, including spinal 
manipulation, yoga, acupuncture, and massage, in conjunction with 
conventional approaches. Individuals suffering from chronic pain 
conditions, their healthcare providers, and health policymakers all 
need better evidence regarding the value and safety of these 
complementary and integrative approaches in alleviating pain, and in 
improving quality of life.
    To address this critical need, NCCAM is intensifying its focus on 
determining whether and how CAM interventions add value to existing 
approaches and on understanding their biological mechanisms. In order 
to advance the science and practice of symptom management, NCCAM plans 
to support Centers of Excellence for Research on CAM for Pain in fiscal 
year 2011. NCCAM is also working with our colleagues at the Department 
of Defense to explore ways that CAM mind and body approaches can be 
used in integrative approaches to treat pain, stress disorders, and 
other symptoms. For example, we recently sponsored a joint workshop on 
acupuncture for the treatment of acute pain. We are also investigating 
potential collaborations with the Department of Veterans Affairs to 
advance CAM research and to maximize our investments in bringing relief 
to our wounded warriors.

             STRATEGIES FOR PROMOTING HEALTH AND WELL-BEING

    It is generally accepted and well established that sustaining 
healthy behaviors (e.g., good eating habits and regular physical 
exercise) and modifying unhealthy behaviors (e.g., smoking) reduce 
risks of major chronic diseases. Many CAM and integrative medicine 
practitioners and disciplines employ various interventions (e.g., 
meditation or yoga) to help motivate people to adopt and sustain 
health-seeking behaviors, or to encourage dietary practices (sometimes 
grounded in traditional medical systems) that incorporate a healthy 
food philosophy. Newly emerging evidence suggests that CAM use may be 
associated with greater degrees of health-seeking behavior. While 
causal relationships between CAM use and healthy behavior have not been 
established, the claims and preliminary data deserve investigation 
given the formidable public health challenges in motivating behavior 
change. Research is needed to explore, clarify, and examine the 
hypothesis that certain CAM approaches or practices can, in fact, be 
useful in encouraging better self-care, an improved personal sense of 
well-being, and a greater commitment to a healthy lifestyle.

                        CAM RESEARCH CHALLENGES

    Given the scope and self-care nature of CAM use by Americans, NCCAM 
remains committed to supporting rigorous research that will address the 
need for scientific evidence to help the public and their healthcare 
providers make better-informed decisions about CAM use. For example, 
herbal medicines, dietary supplements, and other CAM natural products 
are readily available to and purchased by consumers, but evidence 
regarding usefulness of many does not exist. In addition, some people 
believe that herbal medicines, dietary supplements, and other CAM 
natural products are inherently healthier or safer than drugs. In fact, 
there are ongoing concerns about safety, including the presence of 
contaminants or adulterants (e.g., conventional drugs) in some CAM 
natural products, and the potential of toxic interactions with drugs or 
other natural products.
    Clinical research to address these needs will remain a cornerstone 
of the CAM research enterprise, but these studies are complex, 
expensive, and time-consuming. NCCAM's strategic approach is to ensure 
that clinical trials of CAM natural products are based on a 
scientifically sound hypotheses and methods that are grounded in basic 
mechanistic and translational research. This foundation facilitates 
design of maximally informative clinical trials that include measures 
of biological effect relevant to the hypothesis (e.g., biomarkers or 
surrogate markers), as well as measures of clinical outcomes.
    Investigators studying mind and body interventions face other 
scientific challenges in designing rigorous research that will address 
the questions of greatest importance to consumers, providers, and 
healthcare policymakers. These include identifying relevant study 
endpoints and defining appropriate experimental designs to test 
interventions. To address such challenges, NCCAM recently collaborated 
with several NIH ICs to sponsor a workshop on control and comparison 
groups for studies of non-pharmacological interventions.\3\
---------------------------------------------------------------------------
    \3\ NCCAM Workshop on Control/Comparison Groups for Trials of Non-
Pharmacologic Interventions, April 26, 2010.
---------------------------------------------------------------------------
                               CONCLUSION

    As established in its third strategic plan, NCCAM is focusing the 
Center's efforts and resources on two compelling areas of public health 
need: better strategies for managing symptoms such as chronic pain, and 
better strategies for promoting health and well-being. In both areas 
there exist promising scientific opportunities for research on CAM 
interventions to contribute to real and meaningful progress in 
addressing common and vexing individual and social problems, and in 
developing more integrative approaches to healthcare and the support of 
healthy behaviors and lifestyles.
    Finally, NCCAM's plan looks to a vision in which scientific 
evidence informs decisionmaking by the public, by healthcare 
professionals, and by health policymakers regarding CAM use. NCCAM will 
continue its multi-pronged efforts to provide world-class information 
about the safety and usefulness of CAM interventions to consumers, and 
to foster dialogue about CAM use between patients and their healthcare 
providers. In addition, a new online resource, tailored to the needs of 
healthcare professionals, is being launched on the NCCAM website. It 
includes information on the safety and efficacy of a range of CAM 
practices, and was developed in response to providers' needs for an 
evidence-based, one-stop resource to help answer their patients' 
questions on CAM.
                                 ______
                                 
   Prepared Statement of Barbara M. Alving, M.D., Director, National 
                     Center for Research Resources

    Mr. Chairman and Members of the Committee: It is a privilege to 
present to you the President's budget request for the National Center 
for Research Resources (NCRR) programs for fiscal year 2012. The fiscal 
year 2012 budget of $1,297,900,000 includes an increase of $41,225,000 
over the comparable fiscal year 2011 level of $1,256,675,000. Funding 
priorities for fiscal year 2012 include the continued support and 
refinement of the Clinical and Translational Science Award program, 
which will reach its targeted number of 60 consortium members later 
this year. Funds will also 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.
    By uniting innovative research teams with the power of shared 
resources across the Nation, NCRR programs provide laboratory 
scientists and clinical researchers with the tools and training they 
need to understand, detect, treat, and prevent a wide range of diseases 
through clinical and translational research. NCRR's diverse yet 
interconnected NCRR programs enable the research of more than 30,000 
NIH-funded investigators nationwide by providing the resources, tools, 
and networking connections.
    This statement is submitted with the recognition of a publically 
announced proposal for reorganization that would result in dissolution 
of NCRR and the transfer of programs to other NIH ICs and Offices.

       BUILDING CLINICAL AND TRANSLATIONAL RESEARCH CAPABILITIES

    NCRR's Clinical and Translational Science Award (CTSA) program is 
transforming biomedical research by building national clinical and 
translational research capacity to speed the translation of laboratory 
discoveries into better treatments for patients. Launched in 2006, the 
CTSA program is a national clinical and translational research 
consortium which now includes 55 medical research institutions in 28 
States and the District of Columbia. The consortium supports research 
by disseminating clinical research informatics tools, forging new 
partnerships with healthcare organizations, and expanding outreach to 
minority and medically underserved communities. The first cohort of 
CTSAs, now re-competing for their next 5 years of funding, have pushed 
scientific discoveries toward novel and promising treatments that 
enable healthcare reform and more cost-effective treatments. For 
instance, research conducted at the University of California, San 
Francisco's CTSA found that reducing salt intake by just a half 
teaspoon per day could help Americans significantly improve their heart 
health, reduce a number of heart-related deaths and potentially save 
millions in healthcare costs. The findings influenced the Food and Drug 
Administration's decision to limit the amount of salt in prepared foods 
and helped support the CDC's salt reduction campaign.
    Importantly, the CTSA consortium serves as a communications hub 
that ensures sharing among sites and accelerates adoption of best 
practices for clinical and translational research. The CTSAs are 
building biomedical research capability by generating new tools and 
resources, such as ResearchMatch.org, a Web-based national recruitment 
registry which matches volunteers with clinical studies seeking 
participants, and the CTSA Pharmaceutical Assets Portal, a public-
private collaboration enabling scientists to learn more about existing 
compounds that are not being actively developed and might be repurposed 
to treat other types of diseases.

                    ENERGIZING RESEARCH COMMUNITIES

    NCRR programs support new investigators and promote new ideas 
through innovative networking collaborations, partnerships, training, 
and career development for clinical and translational scientists. 
Members of the Institutional Development Award (IDeA) program, which 
supports rural and underserved communities, developed the Network of 
IDeA-funded Core Laboratories (NICL) to address common challenges of 
NCRR-funded core laboratories. NICL addresses, develops and 
disseminates sustainable business models for efficient core operations 
and expands access to advanced core resources and expertise. Now 
extended to other NCRR programs, NICL supports, encourages, and 
facilitates resource sharing and collaboration among NCRR-funded cores 
and shared-resource facilities. NCRR programs are also energizing the 
research community with the world's first physician-scholar training 
program on wireless healthcare research, launched through a partnership 
between The Scripps Translational Science Institute (STSI) CTSA and the 
wireless telecommunications company Qualcomm. STSI is positioned to 
become an invaluable resource for this emerging, high-impact field of 
research.

              ADVANCING INNOVATIVE BIOMEDICAL TECHNOLOGIES

    The Biomedical Technology Research Centers (BTRCs) program is 
producing leading edge technologies to accelerate discoveries that help 
researchers who are studying virtually every human disease. At the 
Resource for Magnetic Resonance and Optical Imaging at the University 
of Pennsylvania, researchers are working closely with clinicians to 
improve patient care by developing and promoting ready access to 
imaging tools with the goal of translating novel approaches for imaging 
blood flow through brain tissue and other organs.

            NEW AND BETTER TREATMENTS THROUGH ANIMAL MODELS

    The National Primate Research Center (NPRC) program advances 
research and knowledge in HIV and AIDS, as well as in numerous other 
diseases. The NPRCs have a close relationship with the CTSAs; one 
example is the collaboration between the New England NPRC and the 
Harvard CTSA. The two are jointly examining the observation that 
insulin resistance appears to be a predictor of dementia utilizing a 
monkey model of insulin resistance and an analysis of high-field MRI 
scans in the monkey model conducted by the Harvard CTSA investigators 
who have expertise with MRI in humans. NCRR continues to supply the 
research community with animal models and resources. Through the Link 
Animal Models to Human Disease Initiative (LAMHDI), a Web-based 
resource, investigators can identify and locate useful animal models 
that are essential to their research in treatments for human disease.

        EXPANDING RESEARCH CAPABILITIES TO ADDRESS HUMAN HEALTH

    Through the IDeA and Research Centers in Minority Institutions 
(RCMI) programs, biomedical research capacities across the Nation are 
expanding into States with historically low NIH funding and are having 
a direct impact on human health. One example is from the National 
Center for Genome Resources in New Mexico, home of the DNA sequencing 
and bioinformatics core for the New Mexico IDeA Networks of Biomedical 
Research Excellence (INBRE). Scientists used innovative whole-genome 
sequencing and expression analyses to study Multiple Sclerosis (MS) in 
identical twins resulting in the first published genome sequences of 
female twins or individuals with autoimmune disease. It is also the 
first systematic comparison of genomes in identical twins, including 
epigenetic markers and expression profiles. Another study from the New 
Mexico INBRE used next-generation sequencing methods to develop a pre-
conception genetic test for 500+ mutations known to increase the risk 
of numerous rare diseases in children of carriers.
    Another illustrative example is a pilot study, initiated by the 
RCMI Translational Research Network, to study the effect of Vitamin D 
on cardiovascular disease risk factors in African Americans. This study 
is important because racial/ethnic minorities, especially African 
Americans, continue to suffer a disproportionate burden of 
cardiovascular disease. African Americans also tend to have low levels 
of Vitamin D and these low levels have been associated with 
cardiovascular disease risk. Supplementation with Vitamin D may be an 
accessible and affordable intervention.

            PROVIDING A CATALYST FOR RESEARCH COLLABORATION

    Grantee institutions are adopting research networking tools as a 
step toward national networking of people, resources, and data on the 
web. The VIVO project, which is an initiative to enable national 
networking of scientists and resource discovery, is driving the network 
with availability of linked open data about scientists and their work. 
The potential will be realized through their commitment to publish data 
on the web so the information is more easily discoverable and 
connections with other open linked data can be made. VIVO is an open 
source semantic web application linking information automatically from 
institutional and public systems of record to provide detailed profiles 
of scholars and researchers. The power of this semantic web approach is 
the ability for creative visualization of connections not previously 
possible between diverse types of information and data.
    This brief overview of NCRR's programs demonstrates our continuing 
commitment to accelerating clinical and translational research. NCRR 
will continue to advance research through partnerships among its 
programs, other Institutes and Centers at the NIH, and with other 
Federal and non-Federal agencies to advance training and translational 
research opportunities.
                                 ______
                                 
Prepared Statement of Paul A. Sieving, M.D., Ph.D., Director, National 
                             Eye Institute

    Mr. Chairman and Members of the Committee:I am pleased to present 
the President's budget request for the National Eye Institute (NEI). 
The fiscal year 2012 budget of $719,059,000 includes an increase of 
$18,832,000 over the fiscal year 2011 appropriation level of 
$700,227,000. As the director of the NEI, it is my privilege to report 
on the many research opportunities that exist to reduce the burden of 
eye disease.

                  TECHNOLOGIES TO ACCELERATE DISCOVERY

    The causes of common diseases are complex in that there are 
potentially many different environmental factors and genetic variants 
that can contribute to disease. New technologies such as genome-wide 
association studies (GWAS) allow investigators to scan the genomes of 
patients to identify genetic risk variants for common diseases. 
Individually, each of these variants may only contribute to a small 
percentage of cases, so GWAS require many subjects to identify low 
frequency risk variants. In the largest GWAS study in vision research 
to date, NEI investigators recently sequenced DNA from over 18,000 
patients and control subjects and identified three new genes associated 
with age-related macular degeneration (AMD), the most common cause of 
vision loss in older Americans. Two of these genes are involved with 
high-density lipoprotein cholesterol metabolism, implicating a new 
biochemical pathway involved in the pathogenesis of AMD. These findings 
will allow researchers to better understand the disease mechanisms 
underlying AMD and develop therapies that address the root cause of 
vision loss. Glaucoma is another heritable blinding disease where the 
genetic underpinnings are poorly understood. The NEI Glaucoma Human 
Genetics Collaboration, a consortium of clinicians and geneticists at 
12 institutions throughout the United States dedicated to identifying 
the genetic factors associated with glaucoma is conducting a large-
scale GWAS that involves scanning 5,000 DNA samples. The consortium is 
using state-of-the-science technology to sequence the exome, the full 
complement of protein coding regions in the human genome, in a subset 
of patients. The data from these DNA samples are expected to be 
available to the vision research community in 2011.

          TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT

    Positive results of ongoing, pioneering clinical trials of gene 
therapy for Leber congenital amaurosis, a severe, early onset retinal 
disease, have encouraged applications of this approach to many other 
eye diseases. In the past year, NEI investigators demonstrated proof-
of-concept of gene therapy using animal models of AMD, achromatopsia, 
Leber's hereditary optic neuropathy, retinitis pigmentosa, and red-
green color blindness. Previous work with animal models established the 
utility of gene therapy in juvenile retinoschisis, optic neuritis, and 
Stargardt disease. These studies now allow investigators to conduct the 
pre-clinical work necessary to pursue regulatory approval for clinical 
trials. In addition, novel gene delivery systems, such as the use of 
nanoparticles, have shown promise in animal models. Such vectors will 
be helpful in expanding the reach of gene therapy to target a variety 
of ocular tissues such as retinal ganglion cells and the light-
sensitive photoreceptor cells.

         ENHANCEMENT OF EVIDENCE-BASE FOR HEALTH CARE DECISIONS

    For treating the blinding (``wet'') form of advanced AMD, monthly 
ocular injections of a drug, Lucentis, was approved in 2007 by the FDA. 
This was the first effective treatment that not only stopped 
progression of the disease, but also improved vision for many patients. 
Lucentis blocks formation of new, but abnormal blood vessels that leak 
fluid into the central part of the retina that is responsible for keen 
vision. It was developed from another inhibitor of blood vessels, 
Avastin, which since its approval in 2004, has been used to block new 
vessels that form to nourish growth of some cancers. Even before final 
FDA approval of Lucentis, ophthalmologists began using Avastin ``off-
label'' for treating AMD, and today, most AMD patients receive Avastin. 
Given the lack of data regarding the effectiveness of Avastin for AMD 
treatment, in 2007, the NEI had an obligation to patients and 
clinicians to compare the two drugs and to evaluate whether the drugs 
could be used less frequently as needed--called PRN--rather than 
monthly as originally approved for Lucentis. Visual acuity improvement 
was virtually identical (within one letter difference on an eye chart) 
for either drug when given monthly. When each drug was given PRN, there 
also was no difference between drugs. For PRN dosing, patients required 
four to five fewer injections per year compared to monthly treatment 
and still had substantial gains in vision.
    Lucentis was also studied in a comparative effectiveness trial for 
diabetic macular edema (DME), a common sight-threatening complication 
of diabetes in which fluid from leaky blood vessels causes the retina 
to swell. For the past 25 years, DME has been treated with a laser to 
destroy abnormal blood vessels. Although laser therapy slows disease 
progression, the effects are temporary, and repeated treatments can 
damage healthy retinal tissue and impair vision. In recent years, 
ophthalmologists have been supplementing laser treatment with ocular 
injections of either Lucentis, a drug that prevents blood vessel 
growth, or triamcinolone, a corticosteroid to reduce inflammatory 
complications. An ongoing clinical trial comparing the safety and 
efficacy of these two drugs is being conducted by the Diabetic 
Retinopathy Clinical Research Network (DRCR.net), a public-private 
partnership funded by NEI, the Type 1 Diabetes Funding Program, and 
industry collaborators. After 1 year, Lucentis plus laser treatment was 
superior in both safety and efficacy compared to triamcinolone plus 
laser or to laser alone. This landmark clinical trial identified the 
first new safe and effective treatment regimen for DME in more than two 
decades. In addition, the study demonstrated that intravitreal 
triamcinolone, which had been used in 60 percent of patients with DME, 
had significant side effects (cataract and glaucoma) and was not better 
than laser alone. These results are already being used by community 
ophthalmologists to greatly improve the vision and quality of life for 
people living with diabetes.
    Treatment of cataracts in infants is challenging for pediatric 
ophthalmologists and parents. Replacing the opaque lens with an 
artificial lens is critical to prevent permanent loss of vision in the 
eye. After removing the cataract, contact lenses have been the 
preferred method to overcome the loss of the natural lens. However, it 
is difficult and stressful for parents to insert a contact lens into an 
infant's eye. Removing the cataract and surgically implanting a 
transparent intraocular lens (IOL) in adults is common but had not been 
fully characterized in infants. An NEI-supported clinical trial found 
no difference in visual acuity with contact lenses compared to IOLs 1 
year after cataract removal. However, IOLs caused significant numbers 
of surgical complications. Based on these results, the use of contact 
lenses is considered the safest effective treatment for infants with 
cataract.

                      NEW INVESTIGATORS, NEW IDEAS

    The increasingly quantitative nature of the biomedical sciences and 
the explosive growth of genomic, transcriptomic, proteomic, 
metabolomic, neurophysiological and clinical data require that 
investigators work at the interface of biology and computational 
sciences. The NEI is committed to developing the next generation of 
vision researchers and has expanded its institutional training grant 
program with a program in ocular statistical genetics at several 
universities. This program will partner researchers with expertise in 
mathematics, modeling, and computation, fields that are not usually 
affiliated with ocular research, with researchers in all areas of 
vision science to provide state-of-the-art training for a new breed of 
researchers.
                                 ______
                                 
 Prepared Statement of Eric D. Green, M.D., Ph.D., Director, National 
                    Human Genome Research Institute

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2012 President's budget request for the National Human 
Genome Research Institute (NHGRI). The proposed fiscal year 2012 budget 
is $524,807,000, an increase of $13,749,000 from the comparable fiscal 
year 2011 level of $511,058,000.
    This is an exciting time for biomedical research in general and for 
genomics research in particular. NHGRI investments in the development 
of genomic technologies and their application are generating innovative 
and powerful approaches to address a diverse array of biological and 
biomedical questions. In early 2011, after 2-plus years of rigorous 
consultation and planning, NHGRI published a new strategic plan for the 
field of genomics in the premiere scientific journal Nature. This 
comprehensive strategic vision describes the next key steps in the 
herculean journey to decipher the secrets within our genetic code and 
to use those discoveries to empower health practitioners and patients 
in a fashion that leads to improved human health. The strategic plan 
also challenges the broader biomedical community to anticipate the 
scientific and non-scientific achievements that will be necessary to 
implement cost-effective and accessible genomics-based medical care 
(i.e., genomic medicine).

                           ENABLING RESEARCH

    Basic research lays the foundation for understanding the functional 
features within our genome and how disruptions in them can lead to 
disease. In fact, the knowledge gained from basic genomic 
investigations enables scientists and clinical investigators from other 
disciplines to pursue translational research programs to understand 
particular biological pathways or address disease-specific questions. 
The ENCyclopedia of DNA Elements (ENCODE) project and the related model 
organism ENCODE (modENCODE) project are moving forward effectively 
toward their goals of finding all the functional elements in the human 
genome, as well as in the genomes of organisms that serve as important 
models for human biology.
    To stimulate and accelerate multi-disciplinary research, NHGRI has 
funded several Centers of Excellence in Genomic Science (CEGS). In 
addition to pursuing cutting-edge genomics research questions, these 
centers are associated with rigorous training programs that focus on 
groups under-represented in biomedical research. Such efforts aim to 
reinvigorate the biomedical research community by engaging diverse 
expertise and fostering the development of versatile young scientists.
    The unprecedented decreases in the cost of DNA sequencing resulting 
from the NHGRI-stimulated technology development efforts are moving us 
steadily closer to the reality of using genome sequencing as a routine 
part of clinical care. However, even with the three-to-four orders-of-
magnitude drop in DNA sequencing costs that has occurred, sequencing an 
entire human genome remains too expensive for the kind of human 
research studies needed to dissect the small genetic differences 
between individuals that contribute to increased risk for common 
diseases, such as cancer, heart disease, and asthma, because such work 
often requires the study of thousands or tens of thousands of 
individuals. To this end, NHGRI continues to push forward technology-
development initiatives, such as the $1,000 Genome program, to develop 
novel and even more cost-effective DNA sequencing methods. 
Concurrently, the NHGRI-funded large-scale sequencing centers continue 
to use innovative approaches for improving available DNA sequencing 
technologies. These efforts are projected to result in a substantial 
drop in the cost of generating a human genome sequence--to less than 
$25,000 by the end of fiscal year 2011 and less than or equal to 
$15,000 by the end of fiscal year 2012.
    To develop an appropriately broad catalog of information about the 
variation within the genomes of different individuals across the world, 
NHGRI continues to contribute substantially to the international 1000 
Genomes Project. In addition, on behalf of NIH, NHGRI led the effort to 
launch a research partnership with the Wellcome Trust, called the Human 
Heredity and Health in Africa (H\3\Africa) Initiative. This new effort 
seeks to stimulate research within African laboratories to enable 
leading-edge genomic studies to be conducted across the continent. The 
knowledge gained through a deeper understanding of genomic variation in 
African populations will not only lead to improved abilities to study 
genetic diseases in those populations, but will enhance our 
understanding of the complex interplay between environmental and 
genetic factors that influence disease susceptibility and drug 
responses in many diverse populations.

                  BUILDING A FRAMEWORK FOR TRANSLATION

    Building on the tools and knowledge created by these and other 
basic research programs, the joint NHGRI-National Cancer Institute 
(NCI) project, The Cancer Genome Atlas (TCGA), is providing important 
new insights into some of the most vexing forms of malignancy, 
including brain cancer and, more recently, acute myeloid leukemia and 
ovarian cancer. Results from TCGA and associated cancer genomics 
studies by NHGRI-funded investigators point to new therapeutic targets 
and, as recently reported in the Journal of the American Medical 
Association, demonstrate the potential for more precise modes of cancer 
diagnosis and treatment. As a flagship program for NIH translational 
research activities, TCGA is expanding its efforts and will focus on an 
additional 20 major cancers over the next 5 years.
    Beginning in fiscal year 2012, NHGRI will expand its large-scale 
genome sequencing and analysis portfolio to include centers that target 
the study of rare, single-gene (Mendelian) disorders using cutting-edge 
genomic technologies. Rare disease research already is benefiting from 
the new genomic technologies. For example, the causative genes for a 
pair of developmental disorders were discovered recently: Miller 
syndrome, which affects the development of the face and limbs, and 
Kabuki syndrome, which affects facial and cognitive development. These 
two discoveries represent the ``tip of the iceberg'' with respect to 
the identification of altered genes that result in rare diseases, as 
reports of such discoveries are published in the scientific literature 
almost weekly. Another new NHGRI initiative in fiscal year 2012 will 
pilot the use of genome sequencing in clinical care settings, an 
important step towards implementing genomic medicine.
    Complementing the genome sequencing initiatives, the NIH 
Therapeutics for Rare and Neglected Diseases (TRND) program, which is 
currently administered by NHGRI, aims to innovate and accelerate the 
drug development pathway for rare and neglected diseases. As the TRND 
pilot projects move toward their initial milestones, the first full-
scale project portfolio will be launched in collaboration with external 
and internal partners. Likewise, the NIH Chemical Genomics Center 
(NCGC) continues to serve as a national resource for the generation of 
novel chemical ``leads'' to spur inventive directions in candidate drug 
and biological assay identification. This statement is submitted with 
the recognition of the Department's notification to the Congress of an 
NIH reorganization that would establish a new National Center for 
Advancing Translational Sciences (NCATS).

                EARLY OPPORTUNITIES FOR GENOMIC MEDICINE

    The clinical promise of genomics requires strong foundational 
knowledge about the structure and biology of genomes as well as the 
biology of disease. Increasingly, genomics will be used to advance 
medical science and to improve the practice of medicine.
    Cancer genomics (as previously discussed) and pharmacogenomics (or 
genomically guided medication prescription) are anticipated to be 
leading-edge examples of genomic medicine. Successes of the latter 
include the use of genomic information for making decisions about 
administering the antiretroviral drug abacavir, now the standard of 
care for HIV-infected patients. Other promising examples of 
pharmacogenomics involve the use of patient genomic information to 
target the application and dose of tamoxifen to treat breast cancer, 
clopidogrel to treat cardiovascular disease, and the blood-thinner 
warfarin. For cancer genomics, it is expected that genomic profiling of 
tumors will become increasingly routine for making decisions about 
treatment strategies.
    Major advances in the study of common, genetically complex diseases 
also have been seen recently. Over the past 5 years, more than 4,000 
validated associations have been made between a genomic region and a 
common disease (or another specific trait). Studies that identify and 
provide evidence to support the value-added connections between genetic 
factors and observed phenotype (physical traits, clinical symptoms, 
etc.) require substantial investments in time, funding, and resources, 
but are fundamental to translating genomics investments into clinical 
applications. One such initiative, the Electronic Medical Records and 
Genomics (eMERGE) Network, aims to advance the efficiency of this 
scientific approach. This program will enter its second phase in late 
fiscal year 2011, during which it will not only link patients' DNA to 
their electronic medical record information, but also will explore the 
challenges of using the information to inform clinical care in a 
respectful, responsible manner.
    The new NHGRI strategic plan identified several critical cross-
cutting elements that are integral to navigating successfully the path 
to genomic medicine: bioinformatics and computational biology, 
education and training, and the continued study of the societal 
implications of genomics. The major bottleneck in genome science is no 
longer data generation; rather, it is the computational analysis of 
data. Beyond the research setting, the public, and especially 
healthcare providers, need to become much more conversant in genomics. 
To help address the needs of healthcare professionals, NHGRI has 
launched online tools to support genetic and genomic training in health 
professional education programs, including bilingual case studies.
    Moving forward, translating basic genomic knowledge to improve 
human health will continue to rely on innovative technology 
development, large-scale collaborative and, increasingly, multi-
disciplinary efforts, and robust attention to the societal implications 
of genomic advances. Demonstrating utility and feasibility will be 
critical for widespread adoption of genomic medicine; the thresholds 
for defining benefit and harm will vary across stakeholders and 
cultural perspectives. However, overcoming the challenges that 
accompany such a paradigm-changing venture is within reach. The 
research and related programs that NHGRI will pursue over the next year 
will continue to lay the groundwork for an era where individualized 
genomic medicine will become a reality, and the original promise of the 
Human Genome Project will be fulfilled.
                                 ______
                                 
Prepared Statement of Richard Hodes, M.D., Director, National Institute 
                                on Aging

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Institute on Aging (NIA) of the National Institutes of Health (NIH). 
The fiscal year 2012 budget includes $1,129,987,000 which is 
$30,450,000 more than the comparable fiscal year 2011 appropriation of 
$1,099,537,000.
    The National Institute on Aging leads the national effort to 
understand aging and to identify and 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 a comprehensive 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. We also carry out the crucial task of training 
the next generation of researchers who specialize in understanding and 
addressing the issues of aging and old age.
    Approximately 39 million people age 65 and older live in the United 
States, and data from the Federal Interagency Forum on Aging-Related 
Statistics indicate that their numbers will double within 25 years. In 
less than 50 years, the number of ``oldest old''--people ages 85 and 
older--may quadruple. As record numbers of Americans reach retirement 
age and beyond, profound changes will occur in our economic, 
healthcare, and social systems.

          TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT

    NIA supports a comprehensive portfolio of research that builds upon 
basic discovery to develop new preventive, diagnostic, and therapeutic 
interventions for age-related diseases and conditions. For example, 
investigators with the Alzheimer's Disease Neuroimaging Initiative 
(ADNI) have found that changes in the structure of the hippocampus, a 
brain area important to learning and memory, may reflect disease 
progression and effectiveness of potential treatments, and have 
established biomarker and imaging measures that may predict risk for 
cognitive decline and conversion to dementia. Clinical, imaging, and 
biological data from ADNI are available to qualified investigators 
around the world; over 1,700 researchers have signed up for access to 
the ADNI database, and global collaborations have resulted in over 170 
published scientific papers since 2004.
    NIA-supported research to identify Alzheimer's disease (AD) 
biomarkers and gain a deeper understanding of the disease's pathology 
and clinical course has made possible the first revision of the 
clinical diagnostic criteria for AD in 27 years through a joint effort 
of the NIA and the Alzheimer's Association. Unlike the criteria that 
doctors and researchers have been using since 1984, the updated 
guidelines cover the full spectrum of the disease as it gradually 
changes over many years, from the earliest preclinical stages before 
symptoms are apparent through mild cognitive impairment (MCI) and 
advanced dementia. The new guidelines also address the use of imaging 
and biomarkers to determine whether changes in the brain and body 
fluids are due to AD.
    Even under the new guidelines, however, diagnosis of AD remains 
complex. NIA intramural investigators are working toward development of 
an accurate, noninvasive, inexpensive blood test for AD. Last year, 
they found that the amount of a protein called clusterin in the blood 
of AD patients reflected the severity of disease, predicted the 
progression of memory impairment, and may predict brain amyloid burden 
long before the patient develops memory problems. These findings were 
recently replicated by independent researchers, and research is ongoing 
in this promising area.
    A continuing translational research success story for NIH is the 
ongoing development of the compound exendin-4. NIA intramural 
investigators originally developed exendin-4 as a treatment for type 2 
diabetes, but have since found that exendin-4 may act as a 
neuroprotective agent in animal models, and they are now conducting a 
phase II/III clinical trial of the compound in patients with MCI and 
early AD. NIA also supports over 40 drug discovery and development 
projects through our AD Translational and Drug Discovery Initiative, 
including a number of AD pilot clinical trials.
    Other NIA-supported researchers are pursuing the development of 
interventions that will delay disease and dysfunction and even extend 
lifespan. Investigators with the innovative Interventions Testing 
Program found that the drug rapamycin, used to help prevent rejection 
of transplanted organs in humans, extended life span in middle-aged 
mice, and more recently demonstrated that the drug exerts beneficial 
effects early in life. Rapamycin inhibits the mTOR pathway, which helps 
regulate cell growth and proliferation. Building upon these findings, 
in 2010 NIA began soliciting research to identify and characterize 
molecular targets within the mTOR pathway with potential to impact 
health span and lifespan.
    NIA also partners with other agencies and organizations on 
translational initiatives. For example, with the Administration on 
Aging, NIA has established an initiative to support development of 
evidence-based interventions, programs, policies, practices, and tools 
that can be used by community-based organizations to help elderly 
individuals remain healthy and independent in their own homes and 
communities. NIA is also joining ``ambassadors'' from organizations 
interested in the health and well-being of older people to promote 
Go4Life, our new exercise and physical activity website 
(www.nia.nih.gov/Go4Life.)

                  TECHNOLOGIES TO ACCELERATE DISCOVERY

    New GWAS (genome-wide association study) technologies are 
transforming our understanding of the origins of disease and disability 
by facilitating rapid comparisons of the full genomes of thousands of 
individuals. This research may lead to the identification of novel 
disease pathways that can be targeted to develop new treatments. In the 
largest GWAS ever conducted in AD research, scientists with the AD 
Genetics Consortium found that a previously unconfirmed gene variant, 
BIN 1, affects development of late-onset AD and identified four 
additional genetic variants significant for the disease. The genes 
identified by this study may implicate pathways involved in 
inflammation and the movement of proteins and lipids both within and 
between cells as being important in the disease process. In a another 
large GWAS, NIA intramural researchers joined an international research 
consortium to confirm six previously identified genes for Parkinson's 
disease and identify five new genes or loci (an area on the chromosome 
where a gene is thought to be located).
    A new NIA-supported initiative is underway to develop technologies 
to better understand the life span and fate of cells in various tissues 
of aged mammals. In these studies, cells are permanently marked at a 
specific point in the organism's life and those marked cells are 
followed to determine their fate and traits over time. These studies 
will provide important insights into aging at the cell and tissue 
levels.

               USING SCIENCE TO INFORM HEALTH CARE REFORM

    Research that will lead to the identification of more effective and 
less expensive clinical interventions is a high priority for NIA, 
particularly through a broad portfolio of comparative effectiveness 
research (CER). A major CER effort has been NIA's administration, on 
behalf of the Agency for Health Care Research and Quality and the 
Office of the DHHS Secretary, of an initiative identifying ways that 
principles of behavioral economics could be used to encourage 
healthcare providers to incorporate findings from CER studies into 
their practices. Other ongoing CER studies include a randomized trial 
of behavioral economic interventions to reduce risk of cardiovascular 
disease; a study comparing various motivators to increase HIV 
screening; and a study comparing the effects of an intensive exercise 
program vs. stretching and range of motion exercises on ambulation in 
hip fracture patients.
    Surprisingly little definitive evidence exists on the impact 
insuring the uninsured has on their health-related behaviors (including 
healthcare usage) and outcomes. However, NIA-supported investigators 
are currently taking advantage of a remarkable opportunity to develop 
such evidence. For a brief period in 2008, Oregon opened a waiting list 
for enrollment in its previously closed public health insurance program 
for certain low income adults, and then offered randomly selected 
people the opportunity to enroll. By comparing individuals who obtained 
health insurance through this program with otherwise eligible 
individuals who were not selected in the ``insurance lottery,'' the 
investigators are assessing the impact of insurance on healthcare usage 
and health outcomes, including the differing impacts on different 
groups. Understanding the consequences of health insurance coverage 
will be central to evaluating proposals to expand or modify health 
insurance coverage in the United States.
    Recently, NIA-supported investigators studying older populations in 
the United States, England, and 11 European countries found that 
retirement prior to age 65 was associated with a significant decline in 
cognitive performance. The investigators suggest that this may be in 
part because for many people retirement leads to a less stimulating 
daily environment, and the prospect of retirement reduces the incentive 
to engage in mentally stimulating activities on the job. It is possible 
(although not yet proven) that the recent trend of American workers 
delaying retirement may eventually lead to improved cognitive 
performance in this group.

                      NEW INVESTIGATORS, NEW IDEAS

    As the American population grows older, the need for healthcare 
professionals who specialize in the unique needs of older individuals 
is becoming ever more urgent. To address this increase in demand 
effectively, we must foster the development of physician-scientists 
whose research will lead to improved care and more effective treatment 
options for older patients with complex medical conditions. Recently, 
NIA established the Grants for Early Medical/Surgical Subspecialists' 
Transition to Aging Research (GEMSSTAR) program to support physicians 
who seek to become clinician-scientists in geriatric aspects of their 
subspecialty. We anticipate supporting 18 to 20 emerging physician-
scientists in this program.
    Once again, thank you. I welcome your questions.
                                 ______
                                 
 Prepared Statement of Roger I. Glass, M.D., Ph.D., Director, Fogarty 
                          International Center

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2012 President's budget for the Fogarty International 
Center (FIC). The fiscal year 2012 budget of $71,211,000 reflects an 
increase of $1,835,000 over the comparable fiscal year 2011 
appropriation of $69,376,000.
    When it comes to global health, there is no ``them''--only ``us.'' 
\1\ In an increasingly interdependent world, the United States and 
nations around the globe share diseases, as well as the burden that 
these diseases inflict on healthy people. In fact, the interests of the 
American people are well-served when the United States promotes global 
health, as healthy nations are more likely to succeed in economic 
development and enjoy political stability. In addition, Americans have 
a strong humanitarian tradition and have long supported efforts to 
improve the health of people around the world. The U.S. Government 
(USG) has recognized these realities, and has made global health a 
national priority. For these investments to yield the maximum benefit 
however, U.S. and foreign scientists must work together to generate the 
scientific evidence that will inform how best to allocate resources. 
These researchers will contribute the necessary local expertise and 
knowledge to thwart pandemics and fight diseases that prevent societies 
from achieving their full potential. They will also empower nations to 
more effectively improve the health of their own populations. The 
Fogarty International Center plays a unique role at the National 
Institutes of Health (NIH) and in the USG by supporting the development 
of global health research expertise in the United States and abroad.
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    \1\ Global Health Council, Washington, DC.
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                      NEW INVESTIGATORS, NEW IDEAS

    Research advances are more likely occur when investigators study 
diseases onsite to develop health interventions that are responsive to 
local and international priorities. Therefore, Fogarty supports long-
term research and training partnerships between United States and low- 
and middle-income country (LMIC) research institutions, which has 
resulted in the training of more than 5,000 researchers--many of whom 
contribute to major scientific advances. For example, the first results 
from a large clinical trial testing candidate microbicides that use 
anti-retrovirals (ARVs) found that the incorporation of an ARV into a 
vaginal gel was more than 50 percent protective against HIV infection 
when used as directed. This advance is a key step toward empowering 
women with a safe and effective HIV prevention tool. Notably, six of 
the study's authors are current or former Fogarty-sponsored trainees.
    To increase the pool of physicians who have the necessary skills to 
conduct robust and critical health research, and to support country-
driven efforts that enhance the sustainability of gains made under 
PEPFAR, Fogarty is also administering a major new program called the 
Medical Education Partnership Initiative (MEPI)--a joint effort of the 
Office of the Global AIDS Coordinator, HRSA, DOD, USAID, CDC, and NIH. 
MEPI supports institutions in Sub-Saharan African countries and their 
U.S. partners to develop new models of medical education, and to 
strengthen the ability of medical students and faculty to conduct 
research that responds to the health needs of their countries.
    Non-communicable diseases--such as heart disease, stroke, cancer, 
and diabetes--are in fact the leading causes of worldwide mortality, 
accounting for 60 percent of all deaths. According to the World Health 
Organization, 80 percent of this burden is in LMICs, where these 
diseases affect people disproportionately during their most 
economically productive years. Fogarty is addressing this challenge 
through its expanded program on Chronic, Non-Communicable Diseases and 
Disorders across the Lifespan, which will support training of in-
country scientists to conduct research on these diseases. Given the 
high burden of non-communicable diseases in the United States, 
knowledge gained from these research activities can inform domestic 
efforts to prevent and treat these diseases--particularly in low-
resource settings.
    Fogarty also supports the training of U.S. investigators to conduct 
global health research and actively engage in international scientific 
collaborations. These investments directly respond to the overwhelming 
demand for global health opportunities on university campuses across 
the United States, and are helping early career scientists to build 
long-term relationships and acquire skills that will help to ensure 
that the United States continues to be a global leader in health 
innovation.

         ENHANCEMENT OF EVIDENCE BASE FOR HEALTH CARE DECISIONS

    There is a tremendous gap between scientific advances and health 
outcomes in the developing world. Therefore, there is an urgent need to 
bridge the gap between what we know and what we do. Fogarty has 
expanded support for research training in implementation science, which 
generates knowledge and methods to better integrate research findings 
and proven health interventions into health policy and practice.
    For example without a significant shift in global prevalence 
patterns, smoking is projected to cause roughly 8 million deaths 
annually by 2030; notably, more than 80 percent of these deaths will 
occur in LMICs. Fogarty's International Tobacco and Health Research and 
Capacity Building Program addresses the critical role of research and 
local research capacity in reducing the global burden of tobacco 
consumption and the need to generate a solid evidence base that can 
inform effective local tobacco control strategies and health policies. 
The program supports epidemiological and behavioral research, as well 
as prevention, treatment, communications, implementation, health 
services and policy research. In Delhi, India, researchers are testing 
the efficacy and cost-effectiveness of a community-based behavioral 
intervention for tobacco cessation among youth living in low-income 
communities. Such studies can inform efforts to curb adolescent smoking 
in the United States--particularly in resource-poor settings.
    Another example is Fogarty's International Implementation, 
Clinical, Operational, and Health Services Research Training Award for 
AIDS and Tuberculosis program, which supports training of scientists 
and health professionals in developing countries to conduct research-
related to implementation of prevention, care and treatment 
interventions for HIV and/or TB. Researchers supported by this program 
recently made a significant discovery regarding the treatment of 
patients with both HIV/AIDS and TB. In these resource-limited settings, 
a high proportion of patients begin antiretroviral therapy (ART) while 
on TB treatment, and paradoxical tuberculosis-associated immune 
reconstitution inflammatory syndrome (TB-IRIS) is a frequent 
complication of the ART. To address this disease management challenge, 
investigators in South Africa found that a 4-week course of prednisone 
reduced the need for hospitalization and therapeutic procedures, and 
hastened improvements in symptoms, performance, and quality of life--
all without excess adverse events.
    Fogarty has also partnered with the Bill and Melinda Gates 
Foundation and the Foundation for NIH on a study that examines the 
relationship between malnutrition and intestinal infections, and also 
the consequences of these conditions on various aspects of child health 
and development. Investigators across multiple international research 
sites seek to facilitate the design of more targeted, cost-effective 
interventions that will reduce the burden of child morbidity and 
mortality from diarrheal diseases. One area of focus is the impact of 
malnutrition, along with damage to the gut (from repeated and 
persistent episodes of diarrheal disease), on the effectiveness of 
childhood vaccines. In many low-resource settings, the immunity 
conferred by various vaccines is significantly lower than in high-
income countries. A better understanding of the links between nutrients 
and the health and function of the intestinal immune system will likely 
lead to the development of targeted and modified vaccine formulations 
and delivery strategies (e.g., dosing, schedules) for improved control 
of intestinal infections.

                  TECHNOLOGIES TO ACCELERATE DISCOVERY

    With increasing globalization, the need to monitor, diagnose and 
respond to epidemics has risen dramatically. Since 1998, Fogarty has 
supported partnerships between the United States and LMIC research 
institutions to increase the capacity of biomedical scientists to 
design, access and use modern information technology in support of 
health sciences research. These partnerships are training biomedical 
and behavioral scientists, engineers, clinicians, librarians, and other 
health professionals to access, manage, analyze, and share biomedical 
information electronically. They are also training individuals who will 
be capable of developing new informatics applications. This will 
increase the ability of local scientists and institutions to conduct 
multi-site clinical trials and perform international disease 
surveillance and prevention programs. Several Fogarty-supported 
informatics projects have now reached new levels of maturity, expanding 
to form regional networks and leveraging tools and lessons learned to 
benefit more researchers. For example, a program in Brazil is sharing 
its materials with Mozambique, where Portuguese is also the national 
language. Researchers in Peru are building a Latin American training 
network, and a university in South Africa is forming a consortium to 
strengthen biomedical informatics throughout Africa.

          TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT

    Fogarty's International Cooperative Biodiversity Groups program 
supports natural products drug discovery and ethnomedical and 
botanicals research. Investigators supported by this program are 
generating new and exciting leads from natural products that may result 
in new therapeutics for a range of diseases. For example, a promising 
new weapon in the war against malaria may come from seaweed found in 
Fiji, as discovered by Fogarty grantee Dr. Julia Kubanek, a chemical 
ecologist at the Georgia Institute of Technology. She and her team 
discovered that a type of red algae in Fiji has strong anti-malarial 
properties. Animal studies have begun to further explore the compound's 
potential as a new therapeutic.
    In conclusion, to effectively confront complex health issues that 
transcend national boundaries, more scientific collaborations must be 
developed and strengthened. Deep regional expertise enables Fogarty to 
facilitate these scientific collaborations. In the context of advancing 
science and health, Fogarty seeks opportunities to bridge differences 
between countries that might otherwise not engage and to build trust by 
encouraging scientists from around the world to work together to 
address shared health challenges. These partnerships promote goodwill, 
stability and peace, and effectively harness science for diplomacy. As 
the world continues to become more interdependent, international 
scientific partnerships will play a critical role in building bridges 
and in improving health for people worldwide. Working in partnership 
with rest of the NIH, Fogarty's unique programs will continue to enable 
scientists in the United States and abroad to work together to tackle 
the most pressing and complex health challenges of our time.
                                 ______
                                 
  Prepared Statement of Dr. Kenneth Warren, Ph.D., Director, National 
               Institute on Alcohol Abuse and Alcoholism

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Institute on Alcohol Abuse and Alcoholism (NIAAA), of the National 
Institutes of Health (NIH). The fiscal year 2012 budget includes 
$469,197,000 for the NIAAA, which reflects an increase of $11,304,000 
over the fiscal year 2011 level of $457,893,000, comparable for 
transfers proposed in the President's request.

           ALCOHOL AND HEALTHCARE--TRANSFORMING THE LANDSCAPE

    NIAAA-supported research is leading to dramatic changes in the 
understanding of alcohol-related problems and their prevention and 
treatment across the lifespan. By translating this research into new 
and better prevention and treatment approaches we have the ability to 
reduce the heathcare burden due to alcohol and enhance the well-being 
of individuals, their families, and society-at-large.

                          SCOPE OF THE PROBLEM

    According to the World Health Organization, alcohol is among the 
ten leading causes of death and disability worldwide; and according to 
the Centers for Disease Control and Prevention (CDC), alcohol is also a 
major cause of preventable death and disability in the United States. 
As the United States. implements healthcare reform, it is important to 
recognize that alcohol misuse costs our Nation an estimated $235 
billion annually.\1\
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    \1\ Rehm J, et al. The Lancet 373(9682): 2223-2233, June 27, 2009-
July 3, 2009.
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    The consequences of alcohol misuse can affect both drinkers and 
those around them at all stages of life. NIAAA's National Epidemiologic 
Survey on Alcohol and Related Conditions (NESARC) estimates that almost 
18 million people in the United States. ages 18 and older suffer from 
alcohol abuse or dependence (collectively known as alcohol use 
disorders, AUDs). The highest prevalence of alcohol dependence, which 
encompasses a broad spectrum of disease ranging from a single episode 
of a few years duration to a chronic relapsing disorder, occurs among 
18-24 year olds. Of note, more than 85 percent of individuals with an 
AUD do not have another drug use disorder. Returning war veterans 
represent a particularly vulnerable population for developing AUDs that 
co-occur with Post Traumatic Stress Disorder (PTSD) and other mental 
health problems. Chronic, heavy alcohol use can damage tissues and 
organs, most notably in the brain, liver, heart, pancreas, and 
esophagus. According to the CDC, in 2007, alcoholic liver disease 
accounted for over 14,000 deaths and in 2008 was responsible for nearly 
20 percent of U.S. liver transplants.
    Alcohol misuse can also have second hand effects, both direct 
effects of alcohol exposure such as damage to the developing embryo due 
to drinking by the pregnant mother, as well as indirect effects 
experienced by individuals other than the drinker such as car crashes, 
sexual assault, and violence. According to an analysis of NIAAA's 
NESARC, one in four children grow up in a household where alcohol is a 
problem, putting them at risk for short and long-term adverse physical 
and psychological health outcomes.

Research to Practice
    NIAAA-supported research is increasing our understanding of how to 
identify and address alcohol-related problems across the lifespan. 
Research shows that early identification and intervention are key to 
reducing future health problems and can dramatically reduce healthcare 
and other costs for individuals who misuse alcohol and those around 
them.

The Value of Screening and Brief Intervention
    The medical and economic value of screening and brief intervention 
(SBI) to identify and address high risk drinking behavior early has 
been well documented. In fact, according to an analysis in the American 
Journal of Preventive Medicine, SBI for alcohol misuse was ranked 
similarly in cost-effectiveness to screening for colorectal cancer and 
hypertension, and to influenza immunization. Using NIAAA's A 
Clinician's Guide: Helping Patients Who Drink Too Much, SBI can be 
performed efficiently and effectively by primary care clinicians. By 
intervening early, providers are able to offer their patients more 
appealing, accessible options to address their alcohol problems, 
options that are less resource intensive and less expensive than those 
needed to treat more severe forms of dependence. For individuals who 
want to assess and address their drinking behavior on their own, NIAAA 
has developed an interactive Web site and booklet, Rethinking Drinking, 
http://rethinkingdrinking.niaaa.nih.gov. These tools offer evidence-
based information about risky drinking patterns, the alcohol content of 
drinks, and the signs of an alcohol problem, along with other resources 
to help people who choose to cut back or stop drinking. Tools such as 
Rethinking Drinking may benefit those who could ultimately recover from 
dependence without treatment by decreasing the severity and duration of 
dependence. For others it may provide the motivation to seek 
professional help.

Underage and College Drinking
    According to the Substance Abuse and Mental Health Services 
Administration, more than one-fourth of 16-17 year olds drank in the 
past 30 days, and 17 percent engaged in binge drinking, i.e. drinking 
more than five drinks on an occasion. For 18-20 year olds, over one-
third engaged in binge drinking in the past 30 days. According to The 
Surgeon General's Call to Action to Prevent and Reduce Underage 
Drinking, each year underage drinking results in the death of about 
5,000 people under the age of 21 from alcohol-related injuries. This 
number is equivalent to the incoming freshman class at Virginia Tech, 
and greater than the total student body at the United States Naval 
Academy. Given the widespread use of alcohol and high prevalence of 
binge drinking by children and adolescents, and the link between early 
alcohol use and later problems including alcohol dependence, it is 
important to identify children and adolescents who are at high risk for 
alcohol use and/or alcohol use disorders. NIAAA will soon release an 
easy to use two question screener and guide for pediatricians and other 
clinicians who provide medical care to children and adolescents. This 
empirically based screening instrument is devised to identify children 
at elevated risk for using alcohol as well as those who have already 
begun to experiment or are more heavily involved with alcohol. In 
addition to identifying individuals who need any level of intervention, 
health practitioners can also use the screening process to provide 
information to patients and their parents about alcohol's effects on 
the developing body and brain. In collaboration with other Federal and 
non-Federal partners NIAAA will implement and evaluate the new guide.
    Alcohol use is also a serious public health and safety problem 
among college students with adverse consequences that range from poor 
academic performance to alcohol poisoning. NIAAA has an ongoing 
research focus on reducing college drinking and its consequences. 
Research encompasses both individual approaches, such as screening and 
brief intervention in college health centers, and environmental 
approaches including studies on college and community policies. NIAAA 
has also established a College Presidents Working Group to advise the 
Institute.

Exploiting Technology to Improve Treatment
    For those who need treatment, NIAAA seeks to provide more and 
improved options. Individuals experience alcohol differently, for some 
it provides almost immediate euphoria, others can drink much higher 
quantities yet feel relatively little effect. Both types may be at risk 
for developing alcohol dependence. Clinical trials with alcohol 
dependent patients testing a variety of medications suggest that, just 
as their physiological response to alcohol differs, so too does their 
response to a specific treatment; and genes appear to be responsible, 
at least in part, for these differences. Given that alcohol dependence 
is a complex disorder influenced by multiple genes, along with the 
evidence that specific treatments only work for subsets of individuals, 
NIAAA continues to seek additional medications that target different 
molecules and pathways in the brain. A number of medications currently 
prescribed for other indications are being evaluated as 
pharmacotherapies to reduce heavy drinking including: the mood 
stabilizing drug quetiapine, the antiepileptic drug levetiracetum, the 
smoking cessation drug varenicline and the anti-nausea drug 
ondansetron. Recently, clinical trials with ondansetron revealed that 
individuals with specific variations in a gene which encodes the 
serotonin transporter respond better to treatment than individuals 
without these variants. Similarly, individuals with a specific variant 
in the mu opioid gene respond better to the FDA-approved alcohol 
dependence treatment naltrexone than those lacking the variant. The 
identification of additional medications, along with the knowledge of 
what works for whom, will soon make personalized treatment for alcohol 
dependence a reality. NIAAA's efforts to make testing of compounds more 
efficient, its active role in engaging the pharmaceutical industry in 
concert with its willingness to test novel compounds, and its work with 
the FDA to improve guidelines and methodology for alcohol clinical 
trials have greatly accelerated the pace of medications development for 
alcohol dependence.
    In parallel, NIAAA is exploiting technological advances in genomics 
to determine the multiple underlying genetic signatures that contribute 
to the range and severity of alcohol use disorders. As part of the next 
NIAAA NESARC, DNA samples will be collected from an estimated 46,000 
people for use in genome-wide association analyses. The level and 
complexity of information derived from new, large-scale, comprehensive 
genomic studies will facilitate our ability to correlate genetic make-
up with subtypes of alcohol dependence improving our ability to match 
patients with treatments.
    Treating the medical consequences of heavy chronic drinking is also 
a priority. For example, currently liver transplantation is often the 
only viable option for treating advanced liver disease but it is a 
prolonged, expensive and risky process only available to patients who 
maintain abstinence. To expand treatment options, NIAAA is supporting 
studies to test a number of compounds that target progressive stages of 
liver disease including fatty liver and liver fibrosis. In addition, 
seminal research is providing a better understanding of why some 
individuals develop liver cirrhosis whereas others who consume similar 
amounts of alcohol do not. Over-activation of the body's natural repair 
mechanisms may actually promote liver disease, suggesting new targets 
for prevention and treatment of alcoholic and non-alcoholic liver 
disease.
                                 ______
                                 
Prepared Statement of Stephen I. Katz, M.D., Ph.D., Director, National 
      Institute of Arthritis and Musculoskeletal and Skin Diseases

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget for the National Institute of 
Arthritis and Musculoskeletal and Skin Diseases (NIAMS) of the National 
Institutes of Health (NIH). The fiscal year 2012 budget includes 
$547,891,000 which is $14,002,000 more than the comparable fiscal year 
2011 appropriation of $533,889,000.

                              INTRODUCTION

    NIAMS addresses diseases that affect individuals of all ages, of 
all racial and ethnic backgrounds, and across all economic strata; many 
disproportionately affect women and minorities. Some are rare 
disorders, but many are very common, and all have a major impact on the 
quality of people's lives. Twenty-five years of NIAMS-funded research 
has contributed greatly to a variety of new treatment and prevention 
strategies that are reducing the burden the diseases place on 
individuals, their families, and society.

            LEVERAGING BASIC SCIENCE TO IMPROVE PATIENT CARE

    NIAMS research has been the basis for the development and testing 
of many new medications, including biologic therapies for autoimmune 
diseases. The newly approved drug belimumab, the first lupus treatment 
to receive U.S. Food and Drug Administration approval in over 50 years, 
interferes with a molecule that NIAMS-funded researchers showed to be 
involved in the immune dysfunction that characterizes this disorder. 
Other, more recent basic research results suggest another existing 
drug, omalizumab, may prevent lupus-associated kidney damage. NIAMS 
investigators in Bethesda, Maryland, are planning to start testing the 
drug's safety for lupus patients soon.
    Basic research into disease mechanisms also is explaining why some 
therapies do not work as well as expected. In 2003, investigators were 
baffled when two NIAMS-funded clinical trials showed that combining two 
medications (a bisphosphonate and parathyroid hormone) that each 
improve bone mass and prevent fractures did not help people any more 
than either drug did individually. Eight years later, research into the 
mechanisms by which bisphosphonates preserve bone revealed that they 
interfere with parathyroid hormone's bone-forming activity. This 
discovery can help physicians choose drug regimens that are best for 
their patients.

            DEVELOPING TOOLS TO DIAGNOSE AND MONITOR DISEASE

    Improvements in bone health have underscored the importance of 
identifying which of the 40 million Americans \1\ who have low bone 
mass are most likely to break a bone. Several large, NIAMS-funded 
studies have indicated that spine fractures predict both future spine 
fractures and debilitating hip fractures. Researchers recently 
published evidence that women who have mild spine defects may also be 
at risk of hip fractures and could benefit from lifestyle changes or 
drugs that prevent bone deterioration. However, the ability to 
distinguish between deformities related to fragile bones and those from 
other causes is critical. If imaging tools that are under development 
can make this distinction, clinicians will be better able to predict 
patients' risk and monitor responses to therapies. Also, the new tools 
potentially could reduce the cost of clinical trials by allowing 
investigators to assess a medication's effects relatively quickly.
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    \1\ Looker AC, et al. J Bone Miner Res. 2010 Jan;25(1):64-71. PMID: 
19580459.
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    Other researchers are testing whether a specific type of magnetic 
resonance imaging can predict worsening of knee arthritis. Preliminary 
work--using images that are available to the research community through 
a public-private partnership supported by the NIH and various 
companies--is promising. If confirmed, clinicians could use the 
technology to identify patients whose knee cartilage is likely to 
rapidly deteriorate due to osteoarthritis. Moreover, like the imaging 
tools mentioned above, the discovery and validation of structural 
changes that researchers can visualize could lead to shorter, more 
efficient trials of promising disease-modifying agents that may help 
the more than 27 million Americans \2\ who have osteoarthritis pain in 
their knees or other joints.
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    \1\*Lawrence RC, et al. Arthritis Rheum. 2008 Jan;58(1):26-35. 
PMID: 18163497.
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    Many diseases within the NIAMS mission involve pain, fatigue, and 
other difficult-to-measure symptoms. A test to quantify changes in 
these parameters could enhance clinical outcomes research and, 
ultimately, clinical practice. NIAMS is one of several NIH components 
engaged in the Patient-Reported Outcomes Measurement Information System 
(PROMIS) initiative to develop such a tool. In addition to managing 
PROMIS on behalf of the NIH, NIAMS encourages researchers to use the 
resource. For example, NIAMS is funding a study to test questions for 
fibromyalgia patients, along with information collected through PROMIS, 
for development of disease-specific measures that allow investigators 
and healthcare providers to monitor patients more effectively.

  APPLYING GENETICS, GENOMICS, AND OTHER CUTTING-EDGE RESEARCH TO NEW 
                               TREATMENTS

    Researchers have been trying to determine for decades if pain and 
itch send different signals to the brain. Difficulties distinguishing 
the two symptoms at molecular and cellular levels had hindered this 
effort, but a group of NIAMS investigators finally identified an itch-
specific molecule. Their work also illuminated a previously elusive 
mechanism by which the itch message travels through the spinal cord to 
be perceived by the brain. Such a discovery should pave the way for 
studies into how chronic itch develops, and make it possible, for the 
first time, to design better treatments.
    Research is providing hope to patients with epidermolysis bullosa 
(EB), a group of rare, inherited blistering skin conditions. When 
investigators repaired the genetic defect in an EB patient, NIAMS-
funded scientists wondered if gene therapy might also work for another 
form of the disease. The strategy seemed promising in a mouse model of 
recessive dystrophic EB (characterized by large, painful blisters, open 
wounds, and early death due to cancer). A first-in-human clinical trial 
will begin this year.
    NIAMS also is funding a Phase I clinical trial that suggests that a 
different gene transfer approach may correct the molecular defect 
underlying type-2 limb-girdle muscular dystrophy (LGMD-2D). The study, 
supported through one of the Senator Paul D. Wellstone Muscular 
Dystrophy Cooperative Research Centers, demonstrated that the procedure 
could safely produce the corrected protein for at least 6 months. The 
data provide a framework that investigators can use when designing 
subsequent LGMD-2D clinical trials. Furthermore, researchers can 
leverage the study's findings about immune responses as they develop 
gene-based therapies for other diseases.
    In the past 12 months, muscular dystrophy researchers also have 
made considerable progress toward understanding the genetic 
underpinnings of facioscapulohumeral muscular dystrophy (FSHD). Prior 
findings from an NIH-funded FSHD patient registry showed that the 
disease is associated with a shorter-than-normal series of repeated 
genetic sequences. Recent technologic advances enabled researchers to 
identify a genetic pattern within these sequences in FSHD patients. 
This discovery, combined with findings that the defects cause FSHD by 
activating a gene and allowing its product to accumulate in muscle, are 
enabling new directions that will accelerate progress. For example, 
researchers can now engineer animal models of the disease, something 
that they could not do without a basic understanding of the genes 
involved.
    Like FSHD, many health problems are influenced by complex genetic 
factors. Over the last few years, the ability of genome-wide 
association (GWAS) approaches to identify gene variants related to 
disease risk has matured from an intriguing concept to a widely used 
scientific tool. These analyses can require thousands of patients, and 
often entail data sharing among NIAMS-funded researchers and scientists 
around the globe.
    An international GWAS team including researchers at the NIH 
Clinical Center showed that a gene involved in the body's immune 
response underlies a person's susceptibility to a painful, inflammatory 
condition called Behcet's disease, which primarily affects people of 
Asian, Middle Eastern, Turkish, or European descent. The gene linked to 
Behcet's disease is associated with other conditions for which 
treatments exist or are being developed. Because of this connection, 
therapies might be available sooner than if the investigators had found 
a completely new disease mechanism.
    In the past year, other genetic studies uncovered additional, 
shared links among diseases. Investigators discovered that rare 
variants of a gene encoding the enzyme sialic acid acetylesterase are 
associated with rheumatoid arthritis and type 1 diabetes, and may play 
a role in other autoimmune diseases. Likewise, researchers leveraging 
the NIAMS-sponsored National Alopecia Areata Registry found that genes 
associated with rheumatoid arthritis and type 1 diabetes are linked to 
the development of alopecia areata, a disease in which the body's 
immune system attacks the hair follicles and causes hair loss. As with 
Behcet's disease, the possibility of a common mechanism is particularly 
exciting because drugs under development for other diseases might also 
be effective against alopecia areata.
    GWAS also holds promise for understanding the genetic differences 
that give rise to more common diseases, such as osteoporosis. The NIAMS 
dedicated funds from the American Recovery and Reinvestment Act of 2009 
toward developing a resource that investigators can use to identify 
molecular changes that influence bone health. The discovery of gene 
variants that protect against osteoporosis or increase a person's risk 
of having low bone mass is likely to suggest targets that researchers 
can pursue when exploring new ways to prevent fragility fractures. 
Moreover, investigators could use genetic markers to identify 
appropriate participants for clinical trials. Data from this effort is 
likely to be available to the wider research community at the end of 
this year.

                               CONCLUSION

    Twenty-five years ago, a few months after Congress passed the 
Health Research Extension Act of 1985 (Public Law 99-158), the NIH 
established the NIAMS. Over the past two and one-half decades, the 
increased emphasis on research on arthritis and musculoskeletal and 
skin disorders has benefited nearly every household in our Nation. We 
are proud of the scientific advances that our researchers have made 
toward helping people who have diseases of the bones, joints, muscles, 
and skin, and are excitedly looking forward to the discoveries they 
will make in the future.
                                 ______
                                 
  Prepared Statement of Roderic I. Pettigrew, Ph.D., M.D., Director, 
      National Institute of Biomedical Imaging and Bioengineering

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Institute of Biomedical Imaging and Bioengineering (NIBIB) of the 
National Institutes of Health (NIH). The fiscal year 2012 budget is 
$322,106,000, which is $8,573,000 more than the fiscal year 2011 
appropriation of $313,533,000. This statement is submitted with the 
recognition of the Department's notification to the Congress of an NIH 
reorganization that would establish a new National Center for Advancing 
Translational Sciences and reallocate the remaining portions of the 
National Center for Research Resources to other parts of NIH, including 
NIBIB.
    The mission of NIBIB is to improve human health by leading the 
development and accelerating the application of biomedical 
technologies. NIBIB invests resources in scientific and technological 
research opportunities at the convergence of the quantitative and life 
sciences, and in training the next generation of researchers. The 
Institute is at the forefront of translating scientific advances into 
engineered medical solutions. Ultimately, NIBIB seeks to realize 
innovations that address healthcare challenges, reduce disease 
mortality and morbidity, and enhance quality of life. To accomplish 
this goal, NIBIB continues to fund bold and far-reaching projects that 
facilitate discovery and translate basic science into new and better 
healthcare.

           TRANSLATIONAL SCIENCE AND THERAPEUTICS DEVELOPMENT

    Biodegradable Home-Based Vaccination System.--Influenza is a major 
cause of morbidity and mortality worldwide. Despite vaccination 
campaigns, the CDC attributes 36,000 deaths and 226,000 
hospitalizations per year in the United States to influenza, with an 
associated cost of approximately $100 billion per year. The number of 
cases could be greatly reduced if more people were vaccinated and if 
the vaccine was more effective. Researchers at the Georgia Institute of 
Technology are addressing both issues by developing a bio-dissolvable 
micro-patch that will allow people to vaccinate themselves. The patch 
is painless, has an application time of just seconds, has no 
biohazardous waste, does not require refrigeration for storage, and 
develops an enhanced immune response to flu. The patch combines cutting 
edge technology and user-friendly simplicity to address this 
significant public health problem.
    Noninvasive Image-Guided Therapy: Focused Ultrasound.--NIBIB 
supports research to develop and promote innovative image-guided 
therapies. One of these technologies is High-Intensity Focused 
Ultrasound (HIFU). HIFU is a non-invasive, image-guided and controlled 
new therapy delivery system which consists of a highly focused beam of 
high-intensity ultrasound that is capable of ablating tissue in a 
targeted region of the body, without harming surrounding tissues. 
Researchers are combining magnetic resonance imaging and HIFU to form 
an image-guided therapy delivery system for non-invasive tumor 
ablation, which can either replace or complement surgery or radiation 
therapy. In addition, transcranial transmission of HIFU can also induce 
the opening of the blood-brain barrier, which allows delivery of drugs 
directly to specific locations in the brain. HIFU for treatment of 
uterine fibroids is now an FDA-approved clinical procedure. These 
developments could revolutionize surgery, cancer therapy and the 
delivery of therapeutic agents in new targeted approaches.
    Regenerative Medicine for Wounded Warriors.--The NIBIB is the lead 
NIH institute for participation in the U.S. Military's signature Armed 
Forces Institute for Regenerative Medicine (AFIRM), now in its third 
year. AFIRM is a multi-institutional, interdisciplinary network to 
develop advanced treatment options for our wounded servicemen and 
women. Researchers are addressing many severe medical conditions 
including burns, compartment syndrome, complex craniofacial injuries, 
limb/digit salvage, and wound healing.

                 TECHNOLOGIES TO ACCELERATE DISCOVERIES

    Monitoring Tumor Cells and Cancer Biology.--NIBIB Quantum Grant 
investigators have successfully developed a test capable of detecting a 
single cancer cell among the billions of normal cells in a blood 
sample. The microchip device, known as the HB-Chip (after the micro 
herringbone pattern on the chip surface), enables the isolation of rare 
circulating tumor cells that may be the source of cancer metastasis. 
Subsequent molecular characterizations of these cells have led to the 
discovery of several subtypes of prostate, breast, and lung cancer. 
These subtypes serve as the basis for customized cancer treatments that 
are tailored to specific patients. The isolation and characterization 
of circulating tumor cells has the potential to revolutionize the 
management of care in cancer patients. Recently, Johnson & Johnson 
announced a partnership with the researchers at Massachusetts General 
Hospital to further develop and market this blood test. ``Stand Up to 
Cancer,'' an organization focused on translational cancer research, is 
supporting four leading cancer centers to launch clinical trials using 
the HB-Chip to determine the sensitivity and specificity of the device 
for various cancers.
    Global Technologies for Disease at the Point of Care.--NIBIB has 
partnered with the Department of Biotechnology and the Ministry of 
Science and Technology in India to support the development of low-cost 
diagnostic and therapeutic technologies that will be used in 
underserved communities worldwide. As the prevalence of chronic 
diseases in low-resource settings increases, PATH (Program for 
Appropriate Technology in Health, a nonprofit organization that 
improves the health of people around the world) is working on new 
initiatives to tackle diabetes. NIBIB-supported researchers are 
evaluating cost-effective technologies to monitor and screen for 
gestational and type 2 diabetes in India. These technologies are also 
applicable to rural and low resource settings in the United States and 
can lead to more effective interventions and therapies.
    In the United States, about 500 mothers die every year during 
childbirth, and in Africa, childbirth-related deaths are nearly 300,000 
annually. Many of these deaths could be prevented if these populations 
had ready access to ultrasound exams, which identify mothers at high 
risk for birth complications. In addition, cardiovascular disease and 
abdominal illnesses could be broadly monitored and managed with wide 
access to ultrasound exams. NIBIB has supported the successful 
development by GE of a hand-held battery powered portable ultrasound 
system (VSCANTM) that costs approximately $8,000 but has the 
features of a conventional hospital or office based system costing 
approximately $200,000. The broad goal is to make ultrasound imaging as 
available as stethoscopes, to facilitate earlier detection and 
monitoring response to therapies.

       TECHNOLOGIES TO IMPROVE EVIDENCE-BASED CLINICAL DECISIONS

    Patients routinely receive their healthcare at multiple locations 
ranging from physician's offices to major medical centers. For optimal 
care, medical records and medical imaging studies must be readily 
available at different sites. To address the need for sharing of images 
and to enhance the adoption of evidence and comparative effectiveness 
in clinical decisions, NIBIB has funded several coordinated projects.
    Patient Controlled Web-Based Access and Sharing of Medical 
Images.--A contract with the Radiological Society of North America 
(RSNA) includes five academic institutions: UCSF, University of 
Maryland, Mayo Clinic, University of Chicago, and Mount Sinai. Two 
additional grants provide support to Wake Forest University and the 
University of Alabama at Birmingham. Each of these projects is 
developing an approach to patient-controlled medical image sharing 
systems for secured image sharing among radiologists and clinicians 
across organizational boundaries. The project at Wake Forest University 
has a special focus on image sharing in rural and under-served areas. 
Validation testing of patient health records that can accept images 
with the appropriate controls and privacy safeguards has begun and will 
start enrolling patients in the near future.
    On Line Decision Support Systems.--NIBIB is providing resources to 
the Brigham and Women's Hospital and the Massachusetts General Hospital 
to implement information technology systems that include clinical 
decision support capability. These systems enable the care providers to 
make clinical decisions that are based on the best available evidence 
and the patient's comprehensive medical data set, including clinical 
images.

                      NEW INVESTIGATORS, NEW IDEAS

    Nanoparticles for Improved Drug Delivery: Overcoming the Mucus 
Barrier.--The delivery of bioactive molecules to target tissues can 
significantly improve drug effectiveness while reducing side effects by 
concentrating medicine at selected sites in the body. While the barrier 
properties of mucus provide protection against infection and other 
potentially toxic particles, they also have thwarted efforts to achieve 
uniform and sustained drug delivery to mucosal surfaces, and have 
likely prevented successful delivery of genes that could potentially 
treat fatal diseases, such as cystic fibrosis. The work of NIBIB 
grantee Dr. Justin Hanes at Johns Hopkins University seeks to 
understand the properties of mucosal barriers and use this knowledge to 
guide the development of polymeric nanoparticulate carriers capable of 
more efficient drug and gene delivery to the respiratory tract, female 
reproductive tract, gastrointestinal tract, surface of the eye, and 
other mucosal tissues for improved therapies. The delivery of bioactive 
molecules to target tissues can significantly improve drug 
effectiveness while reducing side effects by concentrating medicine at 
selected sites in the body.
    Robotic Prostheses for Amputees.--Despite significant technological 
advances over the past decade, state-of-the-art transfemoral prostheses 
are unable to provide power for joint motion. The absence of joint 
power significantly impairs the ability of these prostheses to restore 
many locomotive functions, including walking upstairs and up slopes, 
running, and jumping, all of which require significant net positive 
power at the knee joint, ankle joint, or both. Dr. Michael Goldfarb, an 
NIBIB Edward C. Nagy Young Investigator, recently reported the 
development of the first robotic transfemoral prosthesis with fully 
powered knee and ankle joints. The device allows above-the-knee 
amputees to walk 25 percent faster with less energy than is expended 
with conventional prosthetics and provides increased balance, agility, 
and recovery reflexes to prevent falls. In April, Freedom Innovations 
announced a worldwide licensing agreement for exclusive rights to 
commercialize this device.
    The Institute's emphasis on interdisciplinary approaches to 
biomedical research has provided unprecedented opportunities for 
collaborations among the life and physical scientists leading to 
advances in biology and medicine through the quantitative, physical 
sciences, and engineering perspective, as well as the development of 
technologies that reflect the translation of biological mechanisms. 
These advances will produce remarkable improvements in the health of 
individuals around the world.
                                 ______
                                 
   Prepared Statement of Alan E. Guttmacher, M.D., Director, Eunice 
     Kennedy Shriver National Institute of Child Health and Human 
                              Development

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2012 President's budget request for the Eunice Kennedy 
Shriver National Institute of Child Health and Human Development 
(NICHD) of $1,352,189,000. This reflects an increase of $35,466,000 
over the fiscal year 2011 level of $1,316,723,000.
    In my short time as NICHD Director, the breadth and importance of 
the Institute's mission have already impressed me. Our research changes 
clinical practice and improves health for many people, particularly 
those who may be under-represented in medical research--pregnant women 
and their offspring; adolescents; and people with intellectual, 
developmental, and physical disabilities. Our research shows that even 
simple approaches can have significant impact. For example, a recent 
study found that an inexpensive program teaching newborn care to 
Zambian midwives reduced deaths in the first week of life by 40 
percent. Today, I would like to highlight a few other examples of 
NICHD's recent progress toward improving health, and describe a new 
effort to position our research to continue to contribute to a 
healthier Nation and world.

              IMPROVING HEALTHCARE FOR WOMEN AND CHILDREN

    Thanks partly to NICHD research, Centers for Disease Control and 
Prevention (CDC) data show that the preterm birth rate in the United 
States declined for the second year in a row in 2008. Still, 12 percent 
of all pregnancies end in preterm birth, a leading cause of infant 
death in our country. Preterm infants have greater risk for breathing 
problems, life-threatening infections, cerebral palsy, and 
developmental disabilities. In recent years, NICHD research showed that 
treating pregnant women with a prior history of preterm birth with a 
type of progesterone reduced their risk of another preterm delivery. 
Now, a new study shows that a vaginal gel containing another type of 
progesterone substantially reduces the risk of premature delivery in 
women with a short cervix. With adoption of such treatments, the 
preterm birth rate should drop further.
    Spina bifida, which occurs when the fetal spinal column does not 
close properly, affects nearly 1,500 U.S. infants a year, according to 
the CDC. The most common and severe form of spina bifida, 
myelomeningocele, can cause paralysis, problems with nerve function, 
and brain damage. Recently, the NICHD reported an important trial, the 
Management of Myelomeningocele Study (MOMS). MOMS researchers compared 
standard surgical repair of the spinal cord after birth to repair while 
the fetus is in utero. They found that repairing the spinal cord in the 
womb greatly reduced risk of death and the need to divert fluid from 
the brain. It also doubled the chance of walking and improved later 
motor and cognitive development. Infants undergoing prenatal surgery, 
however, were also more likely to be born preterm, and their mothers 
more likely to experience a uterine tear in childbirth. While 
researchers continue to study this specialized surgery, the initial 
findings promise to improve the quality of life for thousands of 
children.
    New findings also can improve healthcare for women: NICHD 
researchers recently showed that women's cholesterol levels correspond 
with monthly changes in estrogen levels. On average, the total 
cholesterol level of the women studied varied 19 percent over the 
course of the menstrual cycle. Although previous data showed that 
estrogen-containing oral contraceptives or menopausal hormone therapy 
could affect cholesterol levels, this was the first study to show 
conclusively that the cyclical levels of naturally occurring hormones 
have similar effects. This natural variation suggests that clinicians 
should consider the phases of a woman's monthly cycle when evaluating 
her cholesterol levels and before prescribing treatment to help protect 
women against heart disease.

        NEW TECHNOLIGES ADVANCE HOPE FOR AUTISM AND PARKINSON'S

    Autism spectrum disorder (ASD) encompasses a range of conditions 
involving impaired social interactions and communication, atypical 
behaviors, and health problems. While ASD is known to have genetic 
components, researchers have not identified a consistent pattern of 
variant genes. In fact, dozens of gene variants, along with other 
factors, are now linked with ASD, complicating, but also advancing, our 
understanding of the condition and ability to develop new treatments. 
Using advanced imaging technology, NICHD-supported researchers 
identified a gene that impairs communication between parts of the 
brain. Additional genetic studies may reveal ASD subtypes and how 
certain genes function and interact with each other. This research 
could help individualize treatments based on a child's genetic profile. 
New technologies also hold promise for other neurologic conditions, 
such as Parkinson's disease, which results from a loss of brain cells 
that help coordinate movement. NICHD-supported researchers injected 
stem cells from the endometrium (lining of the uterus) into the brains 
of mice with a laboratory-induced form of the disease. These new cells 
took over the function of the brain cells eradicated by Parkinson's. 
This is the first time that scientists showed endometrial stem cells 
could assume the properties of the tissue into which they were 
transplanted. Since endometrial stem cells are widely available, this 
suggests that women with Parkinson's disease might serve as their own 
stem cell donors, or healthy endometrial stem cells might be stored and 
later matched to individuals with the disease.

              TRANSLATING SCIENCE TO ADVANCE REHABILATION

    Applying basic scientific findings to clinical problems can help 
scientists develop new diagnostics or therapeutics for many conditions. 
For instance, NICHD researchers seeking to understand how the vitamin 
folate is metabolized found that the vitamin appears to promote healing 
in rats with damaged spinal cord tissue. Up to 20,000 people yearly 
suffer a spinal cord injury, and about 200,000 people currently live 
with such injuries, according to the National Center for Injury 
Prevention and Control. Folate, a B vitamin that naturally occurs in 
leafy green vegetables and other foods, plays an important role in 
early embryonic brain and spinal cord development. Further 
translational studies on folate could lead to new techniques to help 
regenerate nerve fibers and heal damaged nervous system tissue.

                  THE NATIONAL CHILDREN'S STUDY (NCS)

    The NCS is designed to examine the effects of genetic factors and a 
broad range of environmental factors such as physical environment and 
family, community, and cultural influences on the development and 
health of children in the United States over time. The NCS will yield a 
rich repository of environmental and genetic/genomic data and 
biospecimens that can be mined by scientists for years to come and help 
answer questions concerning the earliest origins of health and disease. 
Over the past year, the NCS has been in a pilot phase, known as the 
``Vanguard Study,'' enrolling about 650 children in 37 sites as of 
February 2011. Three separate recruitment strategies are being tested 
to optimize participation and cost management. During the coming year, 
a range of experts will review ongoing findings, allowing staff to 
develop, by late summer 2011, evidence-based cost-estimates and 
recommendations for the initial phase of the Main Study.

                         VISION FOR THE FUTURE

    The NICHD has embarked on crafting a vision for the future that 
inspires the institute and its partners to achieve critical scientific 
goals and meet pressing public health needs. In early 2011, in a series 
of workshops, we asked leading scientific and health experts to 
identify what the scientific future should look like in 10 years and 
what knowledge must be obtained to reach these new frontiers. We 
focused on such areas as plasticity, development, cognition, behavior, 
reproduction, pregnancy and pregnancy outcomes, developmental origins 
of health and disease, environment, and diagnostics and therapeutics. 
Resultant white papers are posted on our website for additional public 
comment. In June, we will assemble another diverse group of experts to 
refine these concepts and identify those that are most promising. We 
will publish the final vision document by early 2012, helping to ensure 
that NICHD addresses the most important science for the Nation's women, 
children, families, and individuals with special needs.
    Mr. Chairman and members of the Committee, thank you for your 
continued support of NICHD's important work. I would be pleased to 
respond to any questions.
                                 ______
                                 
 Prepared Statement of Nora Volkow, M.D., Director, National Institute 
                             on Drug Abuse

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Institute on Drug Abuse (NIDA). The fiscal year 2012 budget of 
$1,080,018,000 includes an increase of $30,377,000 over the comparable 
fiscal year 2011 level. The following statement updates NIDA's 
scientific progress in addressing drug abuse and addiction. These 
public health problems cost our society more than $600 billion annually 
in health- and crime-related costs and losses in productivity, not to 
mention incalculable personal and social devastation (ONDCP 2004; Rehm 
et al. 2009; CDC 2007). NIDA has crossed a threshold into a new 
research era, unprecedented in its scope, and transformative in its 
prevention, treatment, and policy implications for substance use 
disorders (SUDs).

         RETURN ON INVESTMENT: TECHNOLOGIES TO SPEED DISCOVERY

    New technologies and scientific breakthroughs continue to generate 
actionable information about the genetics, chemistry, and circuitry of 
the human brain. This knowledge has dramatically enhanced our 
understanding of the underlying vulnerabilities and the long-term 
effects of addiction on neurophysiology and behavior. Continuing 
advances in DNA sequencing and analytical tools have transformed the 
landscape of genomic exploration. For example, we can now engage in 
high resolution and accurate sequencing of vast genomic tracts, from 
many different individuals, to systematically search for and identify 
addiction risk variants, which may open up new targets for medications. 
Also, we are dissecting the epigenetic processes that can affect gene 
expression through persistent but reversible changes. Epigenetics 
research has started to help explain the deleterious impact of known 
environmental risk factors, like poverty or chronic stress, on 
vulnerability for SUDs. The burgeoning availability of genetic, 
epigenetic, and environmental data heralds new opportunities for 
translational applications. NIDA is committed to optimizing this 
potential through harmonization efforts that help ensure the 
comparability of pooled data.
    Harmonized databases are crucial for individualized medicine. This 
is clear in the genomics field, but also in the emerging field of 
globally connected biomarkers, or the ``human connectome,'' and for 
brain imaging. NIDA is supporting research to develop biomarkers to 
screen for drug exposure and addiction vulnerability that would be more 
accurate, reliable, and sensitive than current tests (i.e. bodily 
fluids, hair, questionnaires) and would help transform the way SUDs are 
identified and treated.
    Other innovations, such as wireless remote sensing and virtual 
technologies, offer opportunities for transforming how prevention 
messages, real-time monitoring, and even some treatment modalities are 
delivered to the public. Having real-time, objective measures of drug 
use could have a huge impact on SUD treatments. One example is remote 
physiological monitoring (RPM), a rapidly evolving form of telemedicine 
that can track patients' health status (e.g., heart rate, blood 
pressure, skin temperature, and glucose levels) remotely, using devices 
that can store and transmit the results in real-time. NIDA is 
supplementing studies on the use of RPM for monitoring drug use to 
evaluate the effects of treatment interventions and their relationship 
to clinical outcomes. Such data could support the establishment of non-
abstinence endpoints, which in turn could inform the Food and Drug 
Administration (FDA) addiction medications approval process.

             EMERGING PSYCHOACTIVE THREATS TO PUBLIC HEALTH

    The past few years have witnessed several alarming trends, 
particularly prescription drug abuse. Although opioid analgesics are 
among the most effective medications for pain management, they are also 
associated with serious and growing public health problems, including 
drug abuse, addiction, and overdose deaths. The Substance Abuse and 
Mental Health Services Administration reports a six-fold increase in 
treatment admissions for opioid analgesics, from nearly 20,000 in 1998 
to about 120,000 in 2008, while the Centers for Disease Control and 
Prevention acknowledge that unintentional poisonings involving opioid 
analgesics have more than tripled from 1999 through 2007, exceeding the 
total number of deaths involving heroin and cocaine. These trends 
illustrate the challenge of balancing access to critical medications 
for those who need them and preventing their abuse, particularly when 
the public does not perceive their dangers and has much greater access 
to them from a decade-long surge in availability. In 2009, 202 million 
opioid prescriptions were dispensed in the United States making opioids 
the most prescribed class of medications. NIDA is committed to helping 
reverse this trend by providing information on the patterns and 
motivations behind their abuse, sponsoring research on developing pain 
medications with less abuse potential, and creating curricula to 
minimize diversion through better prescribing practices.
    Lingering public misperceptions, particularly among youth, continue 
to hinder our marijuana prevention efforts. The latest Monitoring the 
Future survey of 8th, 10th, and 12th graders reveals that daily 
marijuana use is up for all grades. These teens are not only at higher 
risk of becoming addicted, but they are functioning below optimal level 
at a time when their future depends on peak cognitive performance. Why 
is this happening now? We do not know for sure, but it is reasonable to 
infer that the public debates surrounding medical marijuana have 
increased confusion and lowered the perception of risk, an important 
factor in curtailing use.
    Meanwhile, new drugs routinely emerge and gain rapid notoriety 
thanks to the Internet. Recent examples include ``bath salts'' and 
``spice,'' which are synthetic stimulants and cannabinoids, 
respectively.

         IMPROVING PUBLIC HEALTHCARE--DELIVERY AND PERFORMANCE

    NIDA will continue to leverage our knowledge base into better 
strategies for battling addiction. To further this goal, NIDA takes 
advantage of collaborative research infrastructures designed to deploy 
proven strategies rapidly and effectively. For example, NIDA's Drug 
Abuse Treatment Clinical Trials Network (CTN) tests evidence-based 
treatments in community settings with diverse patient populations, 
optimizing the utility and cost-effectiveness of treatments and 
fostering their adoption. Similarly, NIDA's Criminal Justice-Drug Abuse 
Treatment Studies (CJ-DATS) network promotes multilevel collaborations 
to bring proven treatment models into the criminal justice system, 
disproportionately affected by both drug abuse and HIV. These 
infrastructures allow for the broad testing of promising new 
strategies. One example, called ``Seek, Test, and Treat,'' has great 
potential to improve the public health by expanding access to HIV 
testing and treatment, and ultimately reducing HIV spread.
    Another cornerstone of our strategy is to engage physicians as 
``frontline'' responders to patient substance abuse, providing the 
science-based tools they need to identify potential substance abuse in 
their patients and offering better options for treatment. Recent 
research shows, for example, that compared with methadone, 
buprenorphine results in fewer neonatal abstinence symptoms among 
babies born to opioid-addicted mothers, and is associated with 
decreased hospital stays and thus, costs. To bolster education in the 
treatment of pain, NIDA is leading a multi-Institute effort to create 
Centers of Excellence (CoEs) to develop curricula for medical students, 
nurses, resident physicians, and others. Part of our NIDAMED physician 
outreach initiative, CoEs have also developed and are helping to 
disseminate substance abuse training curricula, woefully neglected in 
most medical training. NIDA continues to encourage physician screening 
of drug abuse with the help of a Web-based interactive screening tool 
that generates clinical recommendations. The broad availability of 
these resources is an important step toward integrating substance abuse 
screening, brief intervention, and referral to treatment (SBIRT) into 
medical care, which will enable better healthcare decisions and 
outcomes.

                 TRANSLATION--THERAPEUTICS DEVELOPMENT

    To help those affected by the disease of addiction, we need to 
expand the pharmacological and behavioral tools available to treat 
SUDs. Thus, medications development is one of the main areas that 
benefits from new discoveries. For example, the century-old practice of 
vaccination has recently been found to be a viable approach for 
treating addiction. In this case, the body itself is coaxed to produce 
antibodies that bind a drug while still in the bloodstream, blocking 
its psychoactive effects in the brain. Already, a nicotine vaccine that 
reduces craving and withdrawal symptoms is in advanced stages of 
development and will be market-ready following approval by the FDA. 
Another strategy has been the development of long-acting, or depot, 
formulations of medications that serve to overcome poor compliance. One 
example is Vivitrol, an extended-release opioid antagonist 
(naltrexone), recently FDA-approved for treating opioid addiction. NIDA 
is now testing the use of depot medications in high-risk groups, such 
as criminal justice offenders, and in regions of the world that have 
high rates of HIV infection and are resistant to treatment with opioid 
agonist medications.
    In parallel, NIDA is supporting research on drug combinations, an 
effective strategy for treating many diseases (e.g., HIV/AIDS, cancer) 
and one starting to show success with addiction. For example, the 
combination of lofexidine (a hypertension medication) and marinol (a 
synthetic form of marijuana's THC) shows promise in treating withdrawal 
symptoms among marijuana-addicted individuals. Early results also 
suggest that a buprenorphine-naltrexone combination could be effective 
in treating cocaine addiction.

                      NEW INVESTIGATORS, NEW IDEAS

    To help sustain our commitment to the next generation of biomedical 
research scientists, NIDA supports multiple training initiatives at 
various career levels and areas of need (e.g., physician scientists, 
computational neuroscience, and medicinal chemists). Examples include 
efforts aimed at mentoring minority investigators and international 
HIV/AIDS researchers, as well as multi-Institute training programs. To 
identify and encourage the next generation of addiction scientists, 
NIDA also awards special prizes at the annual Intel International 
Science and Engineering Fair to high school students whose projects 
exemplify excellent achievement in addiction science.
    In closing, NIDA pledges to continue to tackle the emerging and 
significant public health needs related to drug abuse and addiction, 
taking advantage of unprecedented scientific opportunities to close the 
gaps in our knowledge base and develop and disseminate more effective 
strategies to prevent and treat drug abuse and addiction.
                                 ______
                                 
  Prepared Statement of James F. Battey, Jr., M.D., Ph.D., Director, 
    National Institute on Deafness and Other Communication Disorders

    Mr. Chairman and Members of the Subcommittee: I am pleased to 
present the President's budget request for the National Institute on 
Deafness and Other Communication Disorders (NIDCD) of the National 
Institutes of Health (NIH). The fiscal year 2012 NIDCD budget of 
$426,043,000 includes an increase of $11,244,000 over the comparable 
fiscal year 2011 appropriation of $414,799,000. This statement is 
submitted with the recognition of the Department's notification to the 
Congress of an NIH reorganization that would establish a new National 
Center for Advancing Translational Sciences (NCATS).
    The NIDCD conducts and supports research and research training in 
the normal and disordered processes of hearing, balance, smell, taste, 
voice, speech, and language. Our Institute focuses on disorders that 
affect the quality of life of millions of Americans in their homes, 
workplaces, and communities. The physical, emotional, and economic 
impact for individuals living with these disorders is tremendous. NIDCD 
continues to make investments to improve our understanding of the 
underlying causes of communication disorders, as well as their 
treatment and prevention. It is a time of extraordinary promise, and I 
am excited to be able to share with you some of NIDCD's ongoing 
research and planned activities on communication disorders.

                     AFFORDABLE HEARING HEALTHCARE

    Hearing loss is a serious public health issue and has significant 
social and economic impacts. Approximately 17 percent of American 
adults, or 36 million individuals, report a hearing loss, and only 
about one in five of those individuals who could benefit from a hearing 
aid wears one. Additionally, hearing healthcare and hearing aids are 
only rarely covered by health insurance, and are not covered by 
Medicare. A recent industry survey found that the average cost per 
hearing aid to an individual is $1,600, and for many, the cost is much 
higher. Hearing aids are also consumable devices, often requiring 
replacement every 4-6 years, and frequent battery replacement. This 
makes hearing aids potentially the third highest cost item for an 
individual, following just behind the purchase of a home and car. In 
2009, NIDCD sponsored a workshop, Accessible and Affordable Hearing 
Health Care for Adults with Mild to Moderate Hearing Loss, to examine 
the factors that contribute to hearing healthcare access, 
affordability, and usage; and to develop a set of research objectives 
which could be explored in the future. Based on the recommendations, 
NIDCD published several targeted research initiatives for hearing 
healthcare: to explore new approaches that could lead to improved 
access, assessment, and intervention; to develop methods to determine 
the success of new or improved approaches; and to create small business 
technologies to improve access for underserved patients. The research 
supported through these and other NIDCD-sponsored efforts will enhance 
the evidence-base for hearing healthcare decisions, and provide a 
strong research base for future policy decisions related to affordable 
hearing healthcare.

                                TINNITUS

    Tinnitus--a perceived ringing, buzzing or roaring in the ears--is a 
major public health concern, affecting more than 25 million American 
adults. It can range in severity from a mild condition, requiring no 
medical intervention, to a severe debilitating disease with significant 
physical, emotional, and economic impacts. The Department of Veterans 
Affairs reports tinnitus as the most prevalent service-connected 
disability for veterans receiving disability compensation. More than 
744,000 veterans received service-connected disability compensation for 
tinnitus in fiscal year 2010, presenting a significant cost burden for 
the Nation. Past research has shown that tinnitus is often associated 
with hearing loss; however, little is known about the specific neural 
dysfunctions that lead to the disorder. There are also limited 
treatment options available, and their effectiveness varies widely. In 
response to this need, NIDCD is supporting a strong research portfolio 
on tinnitus. In 2009, NIDCD sponsored a research symposium, Brain 
Stimulation for the Treatment of Tinnitus, to explore the potential 
translation of existing brain stimulation technologies for the 
treatment of tinnitus. Recently, NIDCD supported scientists have 
demonstrated that stimulation of the vagus nerve (a large nerve that 
runs from the head to the abdomen) with an implantable electrode, in 
combination with the playing of tones, is able to ``reset'' the brain, 
eliminating tinnitus in a rat model of the disease. (Vagus nerve 
stimulation is already in use for the treatment of epilepsy and 
depression in more than 50,000 individuals). By varying the tones 
played and the co-stimulation of the vagus nerve, scientists were able 
to abolish the tinnitus sensation and restore the normal function of 
the brain. These exciting findings are the first demonstration of a 
treatment that specifically erases the tinnitus, rather than simply 
masking the sound or providing coping mechanisms for the individual. 
Scientists are now working to translate these findings from the animal 
model into a novel therapeutic strategy for people with severe 
tinnitus.

                         VESTIBULAR PROSTHESIS

    Based on the recent 2008 National Health Inventory Survey, Balance 
and Dizziness Supplement, about 15.5 percent of U.S. adults, or about 
33.6 million individuals, reported they had a problem with dizziness or 
balance in the past 12 months. Balance disorders are one of the reasons 
older people fall, and falls and fall-related injuries, such as hip 
fracture, can have a serious impact on an older person's life. One 
balance disorder which has been particularly difficult to treat is 
Meniere's disease. This disorder causes severe dizziness (vertigo), 
tinnitus, hearing loss, and a feeling of fullness or congestion in the 
ear. NIDCD estimates that approximately 615,000 individuals in the 
United States are currently diagnosed with Meniere's disease and that 
45,500 cases are newly diagnosed each year. While many individuals are 
able to manage the symptoms associated with Meniere's disease through 
diet, drugs, or surgery, up to 2 in 10 do not find adequate relief from 
their symptoms after exhausting all treatment options. NIDCD-supported 
scientists are working to adopt cochlear implant technologies to 
produce a vestibular implant that could counteract vertigo attacks that 
persist despite other treatments. Scientists have already demonstrated 
the ability of a vestibular implant to induce, and provide recovery 
from, vertigo attacks in animal models of Meniere's. Most recently, 
scientists have translated this technology to humans and performed 
their first implantation into an individual. While clinical trials are 
still several years away, this recent breakthrough provides hope to 
many for whom traditional treatments have failed.

                               STUTTERING

    The popularity of the recent Academy Award winning movie, ``The 
King's Speech,'' has brought to light the communication challenges 
faced by approximately 3 million Americans each day. Stuttering can 
affect individuals of all ages, but occurs most frequently in young 
children between the ages of 2 and 6, with boys 3 times more likely 
than girls to stutter. Most children, however, outgrow their 
stuttering, and it is estimated that less than 1 percent of adults 
stutter. For those individuals who continue to stutter into adolescence 
and adulthood, there are limited treatment options. NIDCD supports a 
research portfolio on stuttering to understand the underlying genetic, 
neurologic, and physiologic causes of stuttering, to predict which 
children will continue to stutter, and to develop novel and effective 
therapies for treatment of stuttering. Recently, NIDCD intramural 
scientists pinpointed the first specific genes that underlie 
stuttering. Building on previous studies which identified a genetic 
region linked to stuttering, and harnessing new technologies in genetic 
sequencing, the researchers found mutations in three genes important in 
the recycling of cellular breakdown products inside cells. Different 
mutations in two of these genes are related to severe metabolic 
disorders, called mucolipidosis II and III, which cause joint, 
skeletal, heart, liver, and other health problems, including speech 
problems. The findings may result in the development of new drug 
therapies for individuals who stutter.

        OLFACTORY DEFICITS EARLY WARNING OF ALZHEIMER'S DISEASE

    For several years, it has been know that individuals with 
Alzheimer's disease (AD) often exhibit an impaired sense of smell 
(olfaction), making a smell screening test an attractive opportunity 
for development as a biomarker of disease. However, it was not known 
why AD impacts olfaction. Recently, NIDCD-supported scientists used a 
mouse model of AD to identify pathological changes in the olfactory 
system very early in the animals' lives, indicating a sensitivity of 
the olfactory system to this type of damage. These changes manifested 
well in advance of the onset of changes in other areas of the brain 
involved in memory, and were predicted by the animals' performance on a 
smell discrimination task. In addition, NIDCD-supported scientists have 
used brain imaging of humans to examine changes in brain activity 
during smell discrimination tasks. These imaging studies have 
identified a significant blunting of response in individuals with AD. 
Both of these discoveries could lead to new, non-invasive tools to 
enhance the early diagnosis of AD, and better inform healthcare 
decisions for affected individuals.

                      NEW STRATEGIC PLAN FOR NIDCD

    NIDCD has initiated the development process for a new Strategic 
Plan. In March 2011, NIDCD convened a series of working groups of 
scientific experts in the smell and taste; voice, speech, and language; 
and hearing and balance fields to advise us on emerging scientific 
opportunities in four priority areas: understanding normal function of 
communication systems; understanding diseases and disorders of 
communication systems; improving diagnosis, treatment, and prevention 
of communication disorders; and accelerating translation of research 
findings into practice. In addition, we remain committed to continuing 
our leadership in fostering the development of new investigators in the 
communication sciences. Our staff is currently working to compile these 
priority areas into a document that will guide our research investments 
from fiscal year 2012 through 2016. A draft will be made available for 
public comment later this year and we anticipate publication of our new 
Strategic Plan in January 2012.
    Mr. Chairman, I would like to thank you and Members of this 
Subcommittee for giving me the opportunity to present examples of 
recent research progress and to highlight some programs made possible 
through your support of the NIDCD.
                                 ______
                                 
 Prepared Statement of Dr. A. Isabel Garcia, D.D.S., M.P.H., Director, 
         National Institute of Dental and Craniofacial Research

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute of Dental and 
Craniofacial Research (NIDCR) of the National Institutes of Health 
(NIH). The fiscal year 2012 budget request for NIDCR is $420,369,000, 
which reflects an increase of $11,113,000 over the fiscal year 2011 
enacted level of $409,256,000 comparable for transfers proposed in the 
President's request.
    The NIDCR goal of improving the Nation's dental, oral, and 
craniofacial health is an ambitious one. It demands that we address the 
wide array of diseases and conditions that affect the oral cavity and 
craniofacial structures, including diseases such as dental caries 
(tooth decay) and periodontal diseases that are endemic in the United 
States, as well as birth defects such as cleft lip and palate, chronic 
oral-facial pain conditions, oral and pharyngeal cancers, and oral 
manifestations of systemic diseases, such as Sjogren's syndrome, 
diabetes, and HIV infection. NIDCR is committed to identifying 
effective preventive, diagnostic, and treatment approaches for these 
diseases and conditions. Today, I will describe how we are investing in 
basic discovery and preclinical studies across these myriad areas and 
applying new knowledge to the development of clinical trials and 
studies in humans.

                      ACCELERATING BASIC DISCOVERY

    Joshua Lederberg, who shared the 1958 Nobel prize for discovering 
that bacteria can mate and exchange genes, once quipped about microbes 
that ``you know one when you see it.'' The problem, he explained, is 
that microbes were largely ``invisible'' and noticed only after their 
damage had been wrought. NIDCR-supported researchers and others 
recently identified--made ``visible''--more than 600 distinct microbial 
species as residents of the human mouth. NICDR scientists are also 
systematically exploring how the individual bacterial species assemble 
into biofilms. Biofilms are the living, mat-like microbial communities 
found on many parts of the human body, including our teeth and gums, 
and play a major role in the development of dental and oral disease.
    Microbial biofilms can form on any surface, including on medical 
devices, and are implicated in more than 80 percent of human 
infections. The oral cavity offers tremendous potential both as a 
diagnostic window and an easily accessible model for research aimed at 
understanding the host of bacteria associated with biofilm-mediated 
disease throughout the body. Researchers now possess the tools to 
extract a biofilm sample and determine the identities of most of its 
microbial inhabitants.
    Recently, NIDCR grantees devised a new fluorescent imaging system 
that successfully distinguished among 28 oral microbes within a single 
field of view and that soon will be able to distinguish among at least 
100, providing spatial analysis in three dimensions. Enhanced imaging 
of the oral biofilm will accelerate discovery in studies of biofilm 
formation, organization, and composition and thus the keys to their 
control. This structural understanding will form the basis for research 
aimed at development of tools to combat oral and other infectious 
diseases and improve health.
    An NIDCR grantee and colleagues recently performed a novel type of 
systematic genetic analysis to better elucidate microbial behavior. The 
researchers collected over 4,000 mutant bacterial strains and tested 
them in 324 different environmental conditions. Pulling all the data 
together, the scientists gained a fuller understanding of the 
functional molecular networks governing bacterial response. They also 
gleaned new information about a gene involved in antibiotic resistance 
and the synergy of three common antibiotic drugs.
    Both of the exciting advances described above were spearheaded by 
young investigators on NIDCR training grants, offering prime examples 
of the vital importance of continuing to support new investigators and 
new ideas. NIDCR is committed to developing and strengthening the 
workforce of researchers that can leverage the latest tools of 
discovery and are dedicated to solving urgent problems in oral, dental 
and craniofacial health. To enhance this critical pipeline further, 
NIDCR continues to create innovative new training and career programs, 
such as a new transition path for clinical researchers, as well as an 
initiative to catalyze the formation of multidisciplinary teams led by 
new investigators researching temporomandibular disorders and orofacial 
pain.

         TRANSLATING BASIC SCIENCE INTO IMPROVED PUBLIC HEALTH

    Advances in studying oral microbial communities have the potential 
for rapid impact on research for new, more personally targeted, 
clinical treatment. A team of NIDCR-supported scientists recently 
reported that a microbe called Scardovia wiggsiae appears to be linked 
with severe forms of early childhood caries (ECC), the most prevalent 
chronic childhood disease in the United States. For decades, the oral 
bacterium Streptococcus mutans has been singled out as the primary 
pathogen involved in ECC. The scientists found that S. wiggsiae often 
was present in children with decayed teeth in the absence of S. mutans. 
The discovery of this bacterium's role in ECC offers a future target in 
efforts to identify children at risk and to prevent or stop progression 
of this disease before it leads to destruction of the teeth.
    The burden of craniofacial, oral, and dental disease, particularly 
untreated disease, falls heaviest on lower socioeconomic status (SES) 
groups, which include disproportionately large numbers of racial and 
ethnic minorities. Researchers, including those at the five NIDCR-
supported Centers for Research to Reduce Disparities in Oral Health, 
continue working to identify creative, practical approaches to deal 
with pressing oral health issues, including ECC and oral and pharyngeal 
cancer. These approaches must be inexpensive, easily applied, and 
readily tailored to meet individual and community needs. Three of these 
Centers recently initiated clinical trials to test new interventions to 
prevent ECC among American Indian and Hispanic children and in 
residents of public housing. Children in low SES families are 
particularly vulnerable to ECC's painful and costly impact. Three 
additional trials will launch in fiscal year 2012.

            ENHANCING THE EVIDENCE BASE FOR ORAL HEALTH CARE

    Tackling real-world clinical issues and generating evidence that 
will be of immediate value to practitioners and patients is the central 
goal of the NIDCR-supported dental Practice-based Research Networks 
(PBRNs). Conducting research in dental practices draws on the 
experience and insight of practicing clinicians to help identify and 
frame research questions. Because PBRN studies address practice-based 
problems, their results tend to be more quickly translated into daily 
clinical care.
    Leveraging the infrastructure of established dental practices for 
conducting PBRN studies also can be a powerful and cost-effective means 
to conduct clinical research. For example, the past decade brought 
reports that people who take bisphosphonates, a class of drug 
prescribed for osteoporosis or to treat the bone-wasting effects of 
cancer, can develop osteonecrosis (bone death) of the jaw, or ONJ. To 
address the problem, the three regional PBRNs, taking advantage of 
their presence in practices spanning multiple States, teamed up to 
carry out a collaborative study on ONJ. The study results, published in 
2010, confirmed that bisphosphonate use is a risk factor for ONJ, and 
provided additional important evidence to guide clinicians in their 
treatment of this challenging condition.
    In fiscal year 2012, NIDCR will launch a new National Dental PBRN. 
This single network, more national in scope and more representative of 
a greater variety of practice settings, will provide a framework to 
study and improve the delivery of oral care and will build upon the 
collaboration among the regional networks that was crucial to the 
successes to date. Critical to this effort is an improved capacity to 
collect data electronically. Using an adaptable electronic platform for 
enhanced connectivity, data sharing, and communication within and 
between networks will help providers conduct research effectively and 
efficiently and strengthen the PBRN enterprise.

                   DEVELOPING NEW CLINICAL TREATMENTS

    Each year, about 400,000 people worldwide are diagnosed with cancer 
in the head and neck region. In an effort to identify new treatments 
and improve the stagnant 5-year survival rate that hovers only slightly 
above 50 percent, NIDCR scientists focused their research on the 
immunosuppressive drug rapamycin. This research is now moving from the 
basic and preclinical phases, which included studies in an NIDCR-
developed mouse model, to clinical studies. By fiscal year 2012, 
scientists will be recruiting subjects for a clinical trial to assess 
rapamycin's safety and efficacy in humans.
    Research is also needed to combat harmful treatment side effects 
for head and neck cancers. Many patients with head and neck cancers 
will receive radiation therapy, which has the significant long-term 
side effect of xerostomia (dry mouth). The salivary glands, damaged by 
the radiation used to kill nearby tumor cells, can become less 
permeable to the fluid that naturally flows through them and yield less 
saliva, or stop working altogether. Many functional and quality-of-life 
problems occur when oral tissues are deprived of saliva's protective 
properties, including difficulty chewing and swallowing, burning mouth, 
and greater risk of dental caries and oral fungal infections. Despite 
continuing efforts to eliminate this problem, many patients continue to 
suffer.
    Moving from bench to bedside, NIDCR scientists began the first 
gene-transfer study in people with radiation-induced xerostomia. The 
transferred gene, Aquaporin-1, encodes a protein that conveys fluid by 
forming pores, or water channels, in the cell membrane. The study 
assesses whether the transferred gene will open water channels in the 
duct cells, allowing the rapid movement of water through the duct. In 
fiscal year 2012, NIDCR will issue an initiative to stimulate 
additional research on restoring damaged salivary gland structure and 
function to complement this important clinical advance.
    As these highlights illustrate, NIDCR has made a strong commitment 
to advancing oral health science through efforts in the laboratory, in 
training sites, in dental practices, and in the community. This 
investment is providing new tools and scientific approaches that may 
greatly accelerate the next breakthroughs in oral health research. 
NIDCR will continue to support research that provides new and exciting 
leads that can translate into better ways to prevent, diagnose, and 
manage oral, dental, and craniofacial diseases and disorders. In so 
doing, NIDCR seeks to improve the oral health of the Nation.
                                 ______
                                 
   Prepared Statement of Linda S. Birnbaum Ph.D., D.A.B.T., A.T.S., 
   Director, National Institute of Environmental Health Sciences and 
                            Health Services

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Institute of Environmental Health Sciences (NIEHS) of the National 
Institutes of Health (NIH). The fiscal year 2012 budget includes 
$700,537,000; an increase of $17,400,000 over the comparable fiscal 
year 2011 enacted level of $683,137,000, comparable for transfers 
proposed in the President's request.

                              INTRODUCTION

    Good health is vitally important for all Americans, and it depends 
on a clean and safe environment. Currently, our healthcare system 
expends huge resources controlling a variety of diseases and 
dysfunctions that are known to be at least partially connected with 
environmental exposures: asthma, cancer, developmental disabilities, 
neurological/cognitive deficits, heart attack, and many others. 
Preventing these diseases through prevention of adverse environmental 
exposures could make an enormous difference in reducing healthcare 
costs. At NIEHS, and through NIEHS-funded projects in research 
institutions across the United States, we are bringing all the tools of 
biomedical science to bear on the fundamental questions of the effects 
of environmental exposures to toxic substances on biological systems. 
Environmental health science is advancing at a tremendous rate and new 
tools--genetics, genomics, proteomics, metabolomics, informatics, and 
computational biology, just to name some of these new disciplines--give 
us new insights on how environmental effects happen in our bodies. They 
also point the way toward technologies and testing procedures to 
provide better and more timely information for the use of our agency 
partners who are responsible for policy decisions and regulations.

             ADVANCES IN TOXICOLOGY AND EXPOSURE ASSESSMENT

    With our rapidly increasing understanding of the subtleties of 
biological effects of environmental exposures, we are moving toward a 
new kind of toxicological testing that is less expensive and time-
consuming than our current methods, and also gives us an improved 
understanding of the actual effects on humans. Toxicology is becoming a 
more powerful predictive science focused on making target-specific, 
mechanism-based, biological observations. Alternative assays are 
targeting the key pathways, molecular events, and processes linked to 
disease or injury and incorporating them into a research and testing 
framework. Our National Toxicology Program (NTP) at NIEHS is laying the 
foundation for this new testing paradigm in partnership with the 
National Human Genome Research Institute, the Environmental Protection 
Agency, and the Food and Drug Administration. We are using quantitative 
high-throughput screening assays to test a large number of chemicals. 
The resulting data are being deposited into publicly accessible 
relational databases. Analyses of these results will set the stage for 
a new framework for toxicity testing.
    The NIEHS-led Exposure Biology Program (EBP), part of the NIH 
Genes, Environment and Health Initiative, has resulted in the 
development of dozens of new technological advances for personalized 
measurement of environmental exposures. At a recent workshop, EBP 
investigators presented their prototypes: miniaturized personal 
monitors for black carbon and other air pollutants; a wearable 
nanosensor array for real-time monitoring of exposure to diesel and 
gasoline exhaust; a personal aerosol sensor platform to link children's 
exposures to asthma severity; personal exposure assessment systems for 
chemical toxicants; gene expression biomarkers of airway response to 
tobacco exposure; and biomarkers of organophosphate-linked proteins. 
One prototype of a continuously operating wearable badge that provides 
real-time measurements of chemical toxicants has attracted subsequent 
R&D funding from the Department of Defense to develop this model for 
use by military personnel. Others are being moved into validation 
studies as a next step toward their deployment in environmental health 
research.

      EPIGENETICS, ENDOCRINE DISRUPTERS, AND ENVIRONMENTAL HEALTH

    Our understanding of chemical toxicity has been challenged by the 
new science of epigenetics, which is the study of changes to the 
packaging of the DNA molecules that influence the expression of genes, 
and hence the risks of diseases and altered development. Studies 
indicate that exposures that cause epigenetic changes can affect 
several generations.\1\ This new understanding heightens the need to 
protect people at critical times in their development when they are 
most vulnerable. NIEHS is making key investments in understanding basic 
epigenetic processes and how they are influenced by environmental 
factors. Recently, some of this work has provided a critical resource 
for understanding and characterizing properties of human induced 
pluripotent stem cells.\2\ The development of pluripotent stem cells 
shows promise for research and clinical applications in lieu of 
embryonic stem cells, but many questions remain to be answered about 
their structure, utility, and safety. NIEHS-funded investigators have 
established genome-wide reference maps of DNA methylation (an 
epigenetic marker) and gene expression in previously derived human 
embryonic cell lines and human iPS cell lines, to assess their 
epigenetic and transcriptional similarity and predict their 
differentiation efficiency. A separate report by another NIEHS-funded 
group reported ``hotspots'' of aberrant epigenomic reprogramming in 
human iPS cells.\3\ There are still many questions about the role of 
these important epigenetic processes which will need to be answered 
before iPS cells can be confidently used in research and therapy.
---------------------------------------------------------------------------
    \1\ Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic 
transgenerational actions of endocrine disruptors and male fertility. 
Science 308:1466-1469.
    \2\ Bock C, Kiskinis E, Verstappen G, et al. (2011) Reference maps 
of human ES and iPS cell variation enable high-throughpu 
characterization of pluripotent cell lines. Cell 144(3):439-52.
    \3\ Lister R, Pelizzola M, Kida YS, et al. (2011) Hotspots of 
aberrant epigenomic reprogramming in human induced pluripotent stem 
cells. Nature 471(7336):68-73.
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    Related to the field of epigenetics is the key concept of ``windows 
of susceptibility.'' Research shows that the developmental processes 
that occur at fetal and early life stages are especially vulnerable to 
disruption from relatively low doses of certain chemicals.\4\ \5\ \6\ 
We first saw this in the case of lead and other metals, such as mercury 
and arsenic, which we learned decades ago could harm neurological 
development as a result of fetal and childhood exposures. This concept 
also applies to hormonally active agents which disrupt the endocrine 
system. This is an active area of our research program. For example, 
NIEHS and NTP are funding important studies to fill the gaps in our 
knowledge about bisphenol A (BPA), a widely distributed compound used 
in plastics, can linings, thermal paper, and more. NTP's Center for 
Evaluation of Risks to Human Reproduction determined that there was 
``some concern'' about effects to the brain, behavior, and prostate 
gland in fetuses, infants, and children exposed to BPA.\7\ NIEHS is now 
supporting an aggressive research effort to fill the research gaps in 
this area, especially concerning BPA effects on behavior, obesity, 
diabetes, reproductive disorders, development of prostate, breast and 
uterine cancer, asthma, cardiovascular diseases and transgenerational 
or epigenetic effects.
---------------------------------------------------------------------------
    \4\ Rogan WR, Ragan NB (2003) Evidence of effects of environmental 
chemicals on the endocrine system in children. Pediatrics 112:247-252.
    \5\ Dolinoy DC, Weidman JR, Jirtle RL (2007) Epigenetic gene 
regulation: Linking early developmental environment to adult disease. 
Reproductive Toxicology 23:297-307.
    \6\ Committee on Environmental Health, American Academy of 
Pediatrics (1999) Pediatric environmental health, 2nd edition, pp 9-23.
    \7\ http://www.niehs.nih.gov/news/media/questions/sya-bpa.cfm See 
``What does some concern mean?''.
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    Any consideration of important public health issues in the United 
States. has to include obesity. Environmental exposures are beginning 
to be implicated in the obesity epidemic.\8\ \9\ NIEHS is supporting 
research on the developmental origins of obesity and the theory that 
environmental exposures during development play an important role in 
the current epidemic of obesity, diabetes, and metabolic syndrome. 
There are data showing weight gain in adult rats and mice following 
developmental exposure to a number of different chemicals, such as 
tributyltin compounds,\10\ which have been termed ``obesogens'' by some 
researchers. A groundbreaking workshop on environmental factors in 
obesity and diabetes was sponsored by NIEHS in January 2011. Many 
research gaps still need to be filled, but if these early research 
results are confirmed, we may find it more useful to expand our 
approach to fighting obesity to include not just educating about diet 
and lifestyle but also reducing early life exposure to these 
``obesogenic'' chemicals that might be setting the stage for us to gain 
weight later in life.
---------------------------------------------------------------------------
    \8\ Grun F, Blumberg B (2009) Endocrine disrupters as obesogens. 
Mol Cell Endocrinol 304:19-29.
    \9\ Verhulst SL, Nelen V, Hond ED, Koppen G, Beunckens C, Vael C, 
Schoeters G, Desager K (2009) Intrauterine exposure to environmental 
pollutants and body mass index during the first 3 years of life. 
Environ Health Perspect 117:122-126.
    \10\ Iguchi T, Watanabe H, Ohta Y, Blumberg B (2008) Developmental 
effects: oestrogen-induced vaginal changes and organotin-induced 
adipogenesis. Int J Androl 31:263-268.
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                        PLANNING FOR THE FUTURE

    NIEHS recently began work on the development of a new Strategic 
Plan to set goals for guiding our research investments over the next 5 
years. Our process is designed to bring in information and perspectives 
from a wide variety of sources: community members, advocacy groups, 
agency partners, and scientists from all disciplines.
    In summary, understanding the connection between our health and our 
environment, with its mixture of chemicals, diet and lifestyle 
stressors, is a complex and intricate scientific endeavor. At NIEHS, we 
remain committed to leading the evolution of the field of environmental 
health sciences to meet emerging public health challenges.
                                 ______
                                 
    Prepared Statement of Thomas R. Insel, M.D., Director, National 
                       Institute of Mental Health

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute of Mental 
Health (NIMH) of the National Institutes of Health (NIH). The fiscal 
year 2012 NIMH request of $1,517,006,000 includes an increase of 
$40,981,000 over the fiscal year 2011 appropriated level of 
$1,476,025,000. In my statement, I will underscore the impact that 
mental disorders have on public health in the United States; outline 
examples of NIMH's strategies for reducing the burden associated with 
mental disorders; and, highlight examples of research activities that 
are advancing us toward this goal. I submit this statement with the 
recognition of the Department's notification to the Congress of an NIH 
reorganization that would establish a new National Center for Advancing 
Translational Sciences.

                 PUBLIC HEALTH BURDEN OF MENTAL ILLNESS

    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. The burden of mental illness is 
enormous. In 2009, an estimated 11 million American adults 
(approximately 1 in 20) suffer from serious mental illness.\1\ 
According to the World Health Organization, mental disorders are the 
leading cause of medical disability in the United States and Canada.\2\ 
In contrast to many other chronic medical conditions, mental disorders 
typically begin at an early age, usually before the age of 30. Mental 
disorders, such as schizophrenia, depression, and bipolar disorder, are 
increasingly recognized as the chronic medical illnesses of young 
people.
---------------------------------------------------------------------------
    \1\ SAMHSA. Results from the 2009 National Survey on Drug Use and 
Health: Mental Health Findings (Office of Applied Studies, NSDUH Series 
H-39, HHS Publication No. SMA 10-4609). Rockville, MD; 2010.
    \2\ The World Health Organization. The global burden of disease: 
2004 update, Table A2: Burden of disease in DALYs by cause, sex and 
income group in WHO regions, estimates for 2004. Geneva, Switzerland: 
WHO, 2008.
---------------------------------------------------------------------------
    The annual economic costs of mental illness in the United States 
are enormous. The direct costs of mental health treatment represent an 
estimated 6.2 percent of all healthcare spending,\3\ which, according 
to the Centers for Medicare and Medicaid Services, totals 15.8 percent 
of the gross domestic product. Indirect costs, which include all non-
treatment-related costs such as Social Security disability payments, 
lost earnings, and incarceration, account for an even greater expense 
than the direct costs associated with mental healthcare. A conservative 
estimate places the total direct and indirect costs of mental illness 
at well over $300 billion annually.\4\
---------------------------------------------------------------------------
    \3\ Mark TL, et al. National Expenditures for Mental Health 
Services and Substance Abuse Treatment, 1993-2003. SAMHSA Publication 
No. SMA 07-4227. Rockville, MD: SAMHSA, 2007.
    \4\ Insel TR. Assessing the economic cost of serious mental 
illness. Am J Psychiatry. 2008 Jun;165(6):663-5.
---------------------------------------------------------------------------
    NIMH's mission is not merely to reduce the symptoms and disability 
associated with mental disorders, but to promote recovery, to extend 
healthy life, and ultimately, to discover preventive interventions. In 
the year ahead, NIMH will work toward this mission by fostering and 
facilitating a collaborative approach across the spectrum of mental 
health research approaches--from discovery to dissemination--to make a 
positive change in the lives of people with mental disorders and their 
families.

                  TECHNOLOGIES TO ACCELERATE DISCOVERY

    Funding from the American Recovery and Reinvestment Act of 2009 has 
enabled NIMH to support infrastructure development that will provide a 
framework for future discoveries. One large, collaborative project that 
promises to provide researchers with an invaluable reference tool is 
the Transcriptional Atlas of Human Brain Development. This atlas is 
mapping when and where genes are switched on and off during normal 
brain development, because to understand disorders, scientists must 
first understand what the normal patterns of gene expression are during 
development. The atlas will contain data from 16 brain regions at 11 
developmental stages--ranging from embryonic development to mid-
adulthood. These maps will highlight differences between prenatal and 
postnatal brains, changes across adolescence, and unique patterns of 
gene expression that only occur during development. The first maps from 
the atlas were released this year and will form the foundation for 
future maps and releases.

          TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT

    NIMH-funded researchers are working to translate discoveries from 
basic science into targeted, rapidly acting therapeutics. Current 
antidepressant medications and cognitive behavioral therapies often 
require 6 to 8 weeks to have an effect. Previous NIMH research has 
shown that the drug ketamine can reduce depression, including thoughts 
of suicide, within 6 hours. However, long-term use is associated with 
side effects, and the mechanism by which ketamine works remained 
unclear, until NIMH-funded researchers made a significant discovery in 
2010. They identified how the brain responds to ketamine, as well as 
the molecular mechanism for this rapid response--the rapid activation 
of an enzyme, mTOR, which regulates cell growth, proliferation, and 
survival. The discovery of this cellular mechanism today helps point 
the way to developing practical, rapid-acting treatments for depression 
tomorrow.
    In tandem with this cutting-edge discovery-to-treatment research, 
NIMH is looking into ways to personalize and optimize current 
treatments for depression. While effective interventions do exist, 
there is considerable variation in individual treatment outcomes. The 
Establishing Moderators/Mediators for a Biosignature of Antidepressant 
Response in Clinical Care (EMBARC) study is working to develop a 
collaborative approach among researchers who are focusing on biological 
indicators (biomarkers) of depression. EMBARC researchers hope to 
identify a standard set of biomarkers and other measures that can be 
used to predict which interventions will produce the best treatment 
outcomes for an individual. Taken together with our advancing knowledge 
of ketamine, we can say with confidence that rapid, personalized, and 
effective treatments for depression are close at hand.

         ENHANCEMENT OF EVIDENCE-BASE FOR HEALTHCARE DECISIONS

    NIMH's basic and translational research will improve U.S. public 
health only when they lead to improved mental healthcare. To improve 
the outcomes for people suffering from schizophrenia, NIMH is funding 
the Recovery After an Initial Schizophrenia Episode (RAISE) project--a 
large-scale clinical trial designed to alleviate the long-term 
disability associated with schizophrenia by intervening as early as 
possible after the first onset of symptoms, so that people with the 
disorder can lead more productive, independent lives. RAISE addresses 
the effectiveness of providing early, sustained, and integrated care to 
improve health and life functioning outcomes, and develops strategies 
to facilitate implementation of successful, cost-effective early 
interventions in the U.S. healthcare system. RAISE incorporates 
features necessary for rapid dissemination into community settings, 
thus accelerating the transition from research to practice.
    NIMH has also launched the Mental Health Research Network to 
encourage scientific collaboration among nine established research 
centers that are based in integrated, not-for-profit healthcare 
systems. These systems provide care coverage to a diverse population of 
10 million people in 11 States, and they share rich and compatible data 
resources to support a range of effectiveness research. Researchers 
have begun to use this network to address vital issues, including the 
development of a geographically and ethnically diverse autism research 
registry; a pilot study for a new type of therapy for postpartum 
depression; and, a longitudinal analysis of how suicide warning labels 
on antidepressants affect later suicidality among youth.

                      NEW INVESTGATORS, NEW IDEAS

    The future of discovery and translational research lies in the next 
generation of mental health researchers. NIMH's Biobehavioral Research 
Awards for Innovative New Scientists (BRAINS) program provides support 
to early stage investigators to foster innovative research aimed at 
critical gaps identified by the NIMH Strategic Plan. NIMH also 
recognizes the importance of ensuring that our workforce reflects the 
diversity of backgrounds and perspectives that has made the United 
States a source of innovation. NIMH is leading an NIH Blueprint for 
Neuroscience initiative to enhance diversity in neuroscience through 
undergraduate research education experiences, and has established a 
supplemental funding program to provide underrepresented minority 
scholars with mentored research training in strong institutional 
training programs.

               WORKING COLLABORATIVELY TO COMBAT SUICIDE

    NIMH is committed to collaborating with other Federal agencies and 
private partners to hasten the development of interventions and to 
facilitate their widespread use by those most in need. As an example, 
NIMH has been concerned by the high rate of suicide among our Nation's 
military personnel, and has partnered with the Army to conduct the 
Study to Assess Risk and Resilience of Service Members (Army STARRS)--
the largest mental health study of military personnel ever conducted. 
Early examination of Army STARRS data has begun to reveal potential 
predictors of risk for suicide among soldiers. Researchers plan to 
analyze additional historical data and new survey data collected by 
Army STARRS to confirm and expand upon these findings.
    Suicide among civilians is also of significant concern. 
Approximately 34,500 American lives are lost to suicide each year, 
nearly twice the number lost due to homicide, making it the 10th 
leading cause of death in the United States.\5\ \6\ To combat this 
issue, under the leadership of the Substance Abuse and Mental Health 
Services Administration, NIMH joined the Army, the Centers for Disease 
Control and Prevention, other NIH Institutes, and private partners to 
form the National Action Alliance for Suicide Prevention. NIMH is 
spearheading a Research Prioritization Taskforce on behalf of the 
Action Alliance to develop a strategic research agenda that could 
reduce suicide-related mortality by 20 percent in 5 years, or 50 
percent in 10 years, if fully implemented.
---------------------------------------------------------------------------
    \5\ CDC, National Center for Injury Prevention and Control. Web-
based Injury Statistics Query and Reporting System.
    \6\ U.S. Department of Justice, Federal Bureau of Investigation. 
(September 2009). Crime in the United States, 2008.
---------------------------------------------------------------------------
    Successfully combating mental disorders requires collaboration 
across multiple levels of society; Federal agencies, the research 
community, private industry, and the individuals and families affected 
each day. Despite the tremendous burden of mental disorders, NIMH is up 
to the challenge of bringing all stakeholders to the table, harnessing 
scientific advances, and directing the next generation of research to 
improve the lives of people affected by mental disorders.
                                 ______
                                 
Prepared Statement of John Ruffin, Ph.D., Director, National Institute 
               on Minority Health and Health Disparities

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the National Institute on Minority 
Health and Health Disparities (NIMHD) of the National Institutes of 
Health (NIH). The fiscal year 2012 budget of $214,608,000 includes an 
increase of $5,073,000 over the fiscal year 2011 comparable 
appropriation level of $209,535,000.
    This statement is submitted with the recognition of the 
Department's notification to the Congress of an NIH reorganization that 
would establish a new National Center for Advancing Translational 
Sciences and reallocate the remaining portions of the National Center 
for Research Resources to other parts of NIH, including NIMHD.

                              INTRODUCTION

    Health disparity is an issue of immense proportions with health, 
economic, social and environmental impact for the Nation. Disparities 
in the burden of illness and premature death experienced by racial and 
ethnic minorities, low-income, and rural populations, apply to a broad 
spectrum of disease types. Evidence-based research reveals that health 
disparities are the result of interacting factors that may be genetic, 
biological, environmental, social, economic, or psychological in 
nature. The causes of and solutions to health disparities are 
multidimensional and require multidimensional approaches to improve 
health and eliminate the disparities.
    Health disparities have had a longstanding economic burden on the 
healthcare system. The Affordable Care Act (ACA) included several 
provisions aimed at mobilizing the Nation around actions to confront 
health disparities in order to overcome the multiple barriers faced by 
underserved communities in obtaining quality healthcare. One provision 
in the ACA re-designated the National Center on Minority Health and 
Health Disparities (NCMHD) at the NIH to an Institute--named the 
National Institute on Minority Health and Health Disparities. The NIMHD 
was created to strengthen the base for the acceleration of scientific 
discovery already initiated by the predecessor organization, the NCMHD, 
to understand health disparities and to identify and implement 
strategies to eradicate them across the Nation. In accordance with the 
Affordable Care Act, NIMHD is charged to plan, review, coordinate, and 
evaluate minority health and health disparities research activities 
conducted by the NIH Institutes and Centers (ICs). As health 
disparities transcend many diverse areas of biomedical science and 
public health, this work must involve all of the NIH ICs, and numerous 
Federal Government and non-Federal Government partners.

                    BUILDING ON A DECADE OF PROGRESS

    During the past decade, under the aegis of the NCMHD, the NIMHD 
launched its congressional mandates, and established new programmatic 
initiatives and partnerships, allowing it to create the infrastructure 
required to be at the cutting edge of scientific discovery through its 
independent programs and support for collaborative research, research 
infrastructure development, and outreach projects with partners within 
the NIH, HHS, and beyond.
    The foundation of the NIMHD's research portfolio is the NIMHD 
Exploratory and Comprehensive Centers of Excellence (COE) programs. 
Research in the COEs spans the wide array of diseases, health 
conditions, and complex non-biological factors contributing to health 
disparities. Translational research and the development of appropriate 
health interventions is a particular strength of the NIMHD COEs. The 
NIMHD University of Puerto Rico-Cambridge Health Alliance Research 
Center of Excellence has focused its research on Latino health and 
healthcare disparities, specifically mental disorders, substance abuse 
and asthma. This COE has generated and tested models aimed to improve 
health service delivery to eliminate these disparities. This includes 
multi-level interventions at the provider, individual/family and policy 
levels to reduce health services disparities and has provided 
invaluable data to understand the magnitude of substance abuse 
treatment disparities and the social and economic burden of these 
disparities.
    In addition, NIMHD COEs have assisted in emergency response to 
disasters with health disparities implications such as Hurricane 
Katrina in 2005, and the Haiti earthquake in 2010. NIMHD COEs responded 
to the Haitian earthquake crisis with assistance to Haitian communities 
in south Florida and beyond the borders of the country. These efforts 
have improved the understanding of the global nature of health 
disparities.
    To effectively conduct research, individuals, institutions and 
organizations must have the capacity and access to the resources that 
are necessary to conduct research. NIMHD is a leader in advancing the 
NIH efforts to increase the number of underserved populations 
represented in science and medicine. The NIMHD Health Disparities 
Research and the Clinical Research for Individuals from Disadvantaged 
Backgrounds Loan Repayment Programs (LRP) have supported more than 
2,300 individuals representing multiple disciplines through loan 
repayment of educational loans. More than 60 percent of the LRP 
scholars represent racial/ethnic minority populations. The program has 
incentivized the pursuit of a scientific or health disparities research 
career and many former LRP recipients have been successful in competing 
for other NIH grants. Also, NIMHD offers the opportunity for LRP 
recipients to transition into becoming independent investigators 
through its Disparities Research and Education Advancing our Mission 
(DREAM) program in its Intramural Research Program (IRP). During their 
2-year appointment at the NIH conducting research on health 
disparities, the DREAM fellows work with mentors within the NIH 
Intramural Research Program across different NIH Institutes and 
Centers. After the 2-year period, the DREAM fellows have the option of 
returning to their originating academic institution or to a health 
disparity community to further hone their research skills and complete 
the final 3 years of the program.
    In addition, programs such as the Research Centers in Minority 
Institutions and the new NIMHD Science Education Initiative which 
focuses on promoting science education and increasing the pool of 
individuals from health disparity populations in the science field 
starting from kindergarten through the post-doctoral level, will play a 
key role in advancing the NIMHD's activities in this area.
    There is growing interest in scientific research including health 
disparities research at academic institutions throughout the Nation. 
However, many institutions have limited or no current capacity to 
conduct scientific research. Recognizing the variance in capacity among 
institutions of higher education, the NIMHD has invested considerable 
resources in the enhancement of research infrastructure and capacity of 
less research-intensive institutions through programs such as the NIMHD 
Building Research Infrastructure and Capacity (BRIC) program. Over 
time, the BRIC awards have been instrumental in transforming the 
abilities of some institutions to conduct health disparity research. 
For example, San Francisco State University (SFSU) through the 
development of shared research facilities has resulted in the 
publication of approximately 70 research articles on a variety of 
scientific topics, 76 SFSU students have entered highly competitive 
Ph.D. programs, and BRIC-supported faculty have received more than $13 
million in support to conduct health disparity research. Importantly, 
BRIC support has provided a strong base for institutions to expand 
their graduate level educational programs to include new doctorate 
opportunities to advance health disparities research, as well as the 
development of NIMHD Centers of Excellence.

           A NEW ERA IN THE FIGHT AGAINST HEALTH DISPARITIES

    The next decade will focus on bridging persistent gaps in health 
disparities, sustaining effective investments, and developing and 
adapting innovative approaches to health disparities. NIMHD will lead 
the development, implementation and evaluation of the agency's health 
disparities research agenda in collaboration with the other NIH 
Institutes and Centers. Research on minority health and health 
disparities, research capacity-building and outreach/information 
dissemination priorities across the NIH will emphasize areas such as: 
translational research, genetics and biological factors, global health, 
social determinants of health, behavioral and social sciences, 
innovative health technologies, developing a diverse scientific 
workforce, health informatics capacity, public-private partnerships, 
social networking, and diverse participation in clinical trials.
    NIMHD will advance this health disparities research agenda through 
translational research and dissemination of research findings for the 
benefit of clinical practice and health disparity communities. 
Community and population health intervention studies that map social, 
economic and environmental determinants will provide greater insight 
into the underlying causes of health disparities. In addition, primary 
care and prevention research to inform healthcare reform, improve 
healthcare quality, reduce costs and ultimately improve health outcomes 
for health disparity populations will be examined.
    In today's culturally diverse and technologically advanced society, 
the construction of health messages that do not consider culture, 
history, environments, or literacy levels of certain health disparity 
communities can result in the inability of those communities to receive 
health information. NIMHD is committed to supporting and developing 
vehicles to translate and deliver research findings and health 
information to health disparity communities in a culturally and 
linguistically appropriate manner.

                               CONCLUSION

    While many health disparities concerns of the past decade remain 
pervasive, the NIMHD sees opportunities to accelerate the pace of 
scientific discovery and translation. Within the context of the NIH and 
HHS priorities for eliminating health disparities, the NIMHD will 
intensify and diversify its research focus to elucidate the Nation's 
understanding of health disparities. Research strategies must continue 
to be innovative and the results of this research must reach the 
community at a faster pace. The NIMHD is committed to strengthening its 
research efforts to realize these goals.
                                 ______
                                 
   Prepared Statement of Story C. Landis, Ph.D., Director, National 
             Institute of Neurological Disorders and Stroke

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2012 President's budget request for NINDS. The fiscal 
year 2012 budget is $1,664,253,000. Our mission is to reduce the burden 
of neurological disorders through research. NINDS research has improved 
diagnosis, prevention, and treatment, but the best of medical science 
is still far from optimal for most nervous system disorders. 
Fortunately, advances in understanding the brain and its disorders are 
providing extraordinary opportunities for progress.

           ENHANCING THE EVIDENCE BASE FOR MEDICAL DECISIONS

    U.S. Centers for Disease Control and Prevention statistics show 
that from 1997 to 2007 the stroke death rate in the United States 
decreased 34.3 percent, and the number of stroke deaths declined 18.8 
percent, which translates to thousands of lives saved and thousands 
with reduced disability every year. For decades, NINDS clinical trials 
have contributed to this trend by providing evidence that enables 
physicians to choose the best stroke prevention interventions according 
to each person's risk factors. In April, NINDS stopped a stroke 
prevention clinical trial early because the results were already clear 
\1\. The trial included patients at high risk because of a prior non-
disabling stroke and severe narrowing of arteries to the brain. 
Angioplasty combined with stenting, which opens clogged arteries with a 
tiny balloon and inserts a device to prop them open, plus aggressive 
medical therapy led to a higher risk of stroke than the medical therapy 
alone. Another recent NINDS clinical trial showed that a procedure 
using stents is as safe and effective in preventing stroke as carotid 
endartarectomy, a more invasive surgical procedure to clear arteries, 
in people with certain risk factors.\2\ Follow up to monitor longer 
term results is continuing for both trials. NINDS clinical trials are 
similarly guiding treatment for other diseases. A recent clinical trial 
showed that an older drug, ethosuximide, may be the best first drug to 
test to prevent seizures with minimum side effects in children with 
absence epilepsy, providing much needed guidance for treating this 
common disorder \3\. An NINDS-Department of Veterans' Affairs trial 
showed that surgical implantation of deep brain stimulators (DBS) can 
yield better movement and quality of life than drug treatment for 
people with advanced Parkinson's disease, and more recent results of 
this trial provided information about choosing the best site in the 
brain to implant electrodes for each patient \4\. NINDS currently 
supports 32 multi-site clinical trials to test the safety and 
effectiveness of interventions in stroke, epilepsy, traumatic brain 
injury, multiple sclerosis, muscular dystrophy, and other diseases, and 
more than 120 earlier phase trials that are essential steps toward 
large efficacy trials.
---------------------------------------------------------------------------
    \1\ http://www.nlm.nih.gov/databases/alerts/
intracranial_arterial_stenosis.html.
    \2\ Brott TG et al. Stenting Compared to Endarterectomy for 
Treatment of Carotid Artery Stenosis, New England Journal of Medicine 
363:11-23 2010.
    \3\ Glauser et al. Ethosuximide, Valproic Acid, and Lamotrigine in 
Childhood Absence Epilepsy. New England Journal of Medicine. 362:790-
799 2010.
    \4\ Weaver F. et al. Best Medical Therapy versus Bilateral Deep 
Brain Stimulation for Patients with Advanced Parkinson's Disease: A 
Randomized Controlled Trial. JAMA 301:63-73 2009; Follett et al. 
Pallidal versus Subthalamic Deep Brain Stimulation for Parkinson's 
Disease. New England Journal of Medicine 362:2077-91 2010.
---------------------------------------------------------------------------
                    ADVANCING TRANSLATIONAL SCIENCE

    Since long before the term ``translational'' became common, NINDS 
has pushed development of basic science advances into drug, biologic, 
and device therapies. The first enzyme therapy for inherited metabolic 
diseases, several drugs for epilepsy, the first emergency treatment for 
stroke, and pioneering technology for devices that replace lost nervous 
system function are among advances that NINDS translational research 
made possible. Often, industry capitalizes on NIH basic science 
findings to develop a new therapy. However, rare diseases, bold new 
therapeutic strategies, and new uses for existing drugs are all 
challenges that NINDS is more likely than industry to take on. This is 
especially so now because drug companies, citing the extraordinary 
challenges of brain research, are reducing programs to develop nervous 
system drugs \5\.
---------------------------------------------------------------------------
    \5\ ``R&D Cuts Curb Brain-Drug Pipeline,'' The Wall Street Jounal, 
March 27, 2011.
---------------------------------------------------------------------------
    NINDS launched the Cooperative Program in Translational Research in 
2003 to exploit increasing opportunities from neuroscience research. 
This program supports teams of academic and small business 
investigators to carry out milestone-driven, preclinical therapy 
development for a broad range of neurological disorders. The first 
candidate therapies from this program have moved into clinical testing 
for disorders including stroke, Batten disease, and muscular dystrophy.
    Several NINDS programs meet special translational needs for 
particular diseases. Among these are the Anticonvulsant Screening 
Program, the Specialized Centers of Translational Research in Stroke 
(SPOTRIAS), the Udall Centers of Excellence in Parkinson's Disease, and 
the Wellstone Centers for Muscular Dystrophy Research. NINDS chose 
spinal muscular atrophy (SMA) as the disease to pilot another 
innovative approach to drug development. With experts from academia, 
industry, and FDA, the SMA Project designed a drug development plan and 
is implementing the plan through a ``virtual pharma'' organization that 
engages resources via contracts. Promising drug candidates are now in 
advanced pre-clinical testing, and the Project is working toward 
certification for a clinical trial in 2012. Building on the SMA Project 
strategy, NINDS is leading the NIH Blueprint for Neuroscience in a 
larger scale Grand Challenge on Neurotherapeutics. The challenge goal 
is to develop truly novel drugs that will transform the treatment of 
nervous system diseases. The NINDS Intramural Research Program, which 
has a long record of therapy development, is also accelerating 
translational research under a new Clinical Director. NINDS 
translational programs work closely with all of the NIH-wide programs 
and resources that will become part of the National Center for 
Advancing Translational Sciences (NCATS), and will certainly benefit 
from NCATS programs to catalyze translational research.
    Because novel therapies for several neurological diseases are 
moving toward readiness for clinical testing, NINDS is developing a 
multi-site clinical network to improve the speed and effectiveness of 
the early steps in clinical testing of novel therapies for neurological 
disorders. Better early phase testing will increase the likelihood of 
success in larger and more expensive phase III clinical trials of 
effectiveness. This network will test promising interventions, whether 
they arise from academia, foundations, or industry, and will engage 
expertise much greater than the Institute could dedicate to separate 
networks for each of the many neurological diseases. This is especially 
important for rare disorders, including pediatric diseases. A project 
to validate biomarkers for SMA will be among the network's first 
studies.
    Another major clinical initiative will develop and validate 
biomarkers for Parkinson's disease, that is, measurable indicators of 
the disease process. Biomarkers research, which NINDS supports for many 
disorders, exemplifies another way that NINDS programs can catalyze 
both NIH and industry therapy development efforts. With biomarkers for 
neurodegenerative disorders, clinical trials can determine in months, 
rather than years, whether drugs are slowing the progression of disease 
and understand why a new treatment worked or did not. Better biomarkers 
can reduce the cost of research and speed the development of better 
treatments in NIH and industry.

                ACCELERATING PROGRESS THROUGH TECHNOLOGY

    An extraordinary array of technologies has accelerated progress in 
neuroscience. These range in scale from imaging activity of the 
thinking human brain as people carry out complex tasks, to 
understanding atom by atom how molecules control electrical activity in 
brain cells. This year research demonstrated the power of whole genome 
sequencing to understand Charcot-Marie-Tooth disorder, a peripheral 
nerve disease \6\. This is a harbinger of personalized genomics for 
many diseases. Next generation genomics research is underway for 
several neurological disorders. A ``Center without Walls'' will bring 
together the best possible team, regardless of geography, to apply 
advanced genomics to epilepsy. On another technological frontier, ARRA 
enabled NINDS to accelerate research on induced pluripotent stem cells 
(iPSC's) that can be derived from patients with Parkinson's, 
Huntington's, ALS, epilepsy, and other disorders. A spate of new 
technologies, from methods that label nerve cells with more than a 
hundred different colors, to computerized three-dimensional 
reconstruction of intricate nerve cell circuits, to techniques that 
control the activity of individual nerve cells with light, are arming 
neuroscientists to meet the longstanding challenge of understanding how 
circuits of nerve cells underlie memory, perception, complex movement, 
and other higher brain functions. This has implications for 
understanding autism, epilepsy, Parkinson's, Alzheimer's, and many 
other diseases.
---------------------------------------------------------------------------
    \6\ Lupski JR et al. Whole-genome sequencing in a patient with 
Charcot-Marie-Tooth neuropathy. New England Journal of Medicine 
362:1181-91 2010.
---------------------------------------------------------------------------
              ENCOURAGING NEW INVESTIGATORS AND NEW IDEAS

    When progress against disease is not forthcoming, a gap in basic 
understanding of the normal brain or the disease process is often the 
cause. Physicians and scientists across academia and industry agree 
that basic research propels long-term progress against disease. The 
insight and ingenuity of the research community is the key. Supporting 
a vigorous scientific community and investigator-initiated research are 
thus high priorities throughout NINDS programs and policies. To 
encourage innovative research, for example, the EUREKA (Exceptional 
Unconventional Research Enabling Knowledge Acceleration) program 
complements the NIH Pioneer Awards, New Innovator Awards, and 
Transformative R01's, all of which support neuroscientists. To prepare 
the next generation of neuroscientists, NINDS training and career 
development programs are tailored to the needs of basic and clinical 
researchers, and funding policies favor early stage investigators. 
NINDS encourages cooperative research and promotes sharing through 
several programs. Examples include the Common Data Elements program, 
Human Genetics Resource Center, consortia on induced pluripotent stem 
cells, disease centers programs, and other grants to multi-investigator 
teams. NINDS is improving programs on workforce diversity and health 
disparities based on guidance from an external review and planning 
process that was completed in 2011.

                           CONCLUDING REMARKS

    Neurological disorders present formidable challenges. Nonetheless, 
prospects for progress have never been more encouraging because of 
progress in understanding the nervous system and its diseases at every 
level from molecules through the working human brain. NINDS is 
aggressively pursuing better prevention and treatment with a balance of 
basic, translational, and clinical research, supported through 
investigator-initiated and priority-targeted programs.
                                 ______
                                 
  Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN, Director, 
                 National Institute of Nursing Research

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Institute of Nursing Research (NINR) of the National Institutes of 
Health (NIH). The fiscal year 2012 budget includes $148,114,000 which 
is $3,857,000 more than the comparable fiscal year 2011 appropriation 
of $144,257,000.

                              INTRODUCTION

    I appreciate the opportunity to share with you some of the exciting 
areas of research that we support at the National Institute of Nursing 
Research (NINR). As you know, a unique combination of societal trends 
challenges our Nation's health, including an aging population, 
increased chronic illness and obesity rates, and shortages in the 
healthcare workforce. At NINR, we address these issues by supporting 
research across the life span that: builds the scientific foundation 
for clinical practice; improves quality of life through managing and 
easing symptoms of illness; promotes health and prevents disease 
through biological and behavioral interventions; and enhances end-of-
life and palliative care. We also seek to ensure future discoveries by 
training the next generation of nurse scientists. NINR's emphasis on 
clinical research and training places NINR in a position to make major 
contributions to trans-NIH initiatives to enhance the evidence-base for 
healthcare decisions, promote translational research, and support new 
investigators and new ideas. NINR was established 25 years ago, in 
1986, as the National Center for Nursing Research. This year, we are 
commemorating our 25th anniversary through a series of scientific 
outreach events to celebrate our longstanding emphasis on translating 
science to improve health and clinical practice. In our first event, a 
scientific symposium entitled ``Bringing Science to Life,'' some of our 
distinguished scientists presented cutting edge research on topics as 
varied as: the role of sleep in health and safety; managing chronic 
illness in racially/ethnically diverse groups; testing interventions to 
educate and support parents with premature infants; and understanding 
the biological underpinnings of muscular dystrophy. This Anniversary is 
an opportunity to review what NINR science has accomplished, and more 
importantly, to envision and plan the next phase of evidence-based 
research to meet future health and healthcare needs, challenges, and 
priorities. As we look forward to the next 25 years, we are confident 
that NINR-supported science will play an ever-increasing role in 
addressing the most pressing issues facing our Nation's health. I 
would, next, like to share with you some examples of the research that 
we support and how it improves quality of life.

             CHILDHOOD AND ADOLESCENCE: RISK AND RESILIENCE

    From birth through young adulthood, children and adolescents face 
many health challenges and also demonstrate incredible resilience. NINR 
supports research to promote positive outcomes for children and 
families facing a myriad of challenges. For example, chronic health 
conditions in children, such as diabetes, arthritis, and obesity, pose 
challenges for the entire family and require sustained attention to 
treatment adherence and health assessment. NINR-funded scientists have 
made advances both in understanding the family's role in children's 
health and in improving assessment strategies. One study found that 
although parents detected significant pain in their child following the 
child's surgery, they tended to under-treat it, suggesting that 
educating parents about pain management may be beneficial. Another 
study found that screening children's waist circumference, which can be 
easily implemented in schools, identifies more cases of high blood 
pressure than the usual measure of body mass index alone. A current 
initiative led by NINR aims to improve self-management of chronic 
illness in children. An increasing challenge later in childhood comes 
from HIV, with adolescents and young adults comprising one-third to 
one-half of new infections in the United States,\1\ despite numerous 
prevention campaigns. Moreover, adolescents from racial/ethnic minority 
groups are disproportionately affected.\2\ A new NINR initiative 
supports projects to examine psychosocial, cognitive, and neurological 
predictors of HIV/AIDS risk decisionmaking in adolescents. This 
research will provide an evidence-base to guide future culturally and 
developmentally relevant interventions to prevent HIV/AIDS.
---------------------------------------------------------------------------
    \1\ National Institute for Child Health and Human Development. 
AIDS/HIV. 2008.
    \2\ Centers for Disease Control and Prevention. 2008. HIV/AIDS 
among youth.
---------------------------------------------------------------------------
             CHALLENGES AND CHANGES IN AN AGING POPULATION

    The population of our Nation is aging rapidly, due in large part to 
increased longevity and the aging of the baby boomers. These changes 
are giving rise to significant challenges, resulting in a need for: 
improved strategies to manage co-occurring chronic illnesses; better 
interventions to support family caregivers; and new ways to address 
health disparities and meet the needs of an elderly population that is 
more racially and ethnically diverse than ever before. One pressing 
challenge is the increase in the number of older adults with multiple 
chronic illnesses, such as heart disease, diabetes, and arthritis. Such 
older adults have complex care needs, face long-term self-management of 
illness, and may experience poor coordination of care in the community. 
In a recent NINR-supported Nurse Coordinated Care Intervention, 
advanced practice nurses developed individualized care plans for older 
adults, which included family members and ongoing follow-up care. The 
intervention improved health outcomes and reduced costs of care for 
Medicare patients. A new NINR initiative, that benefits not only older 
adults but individuals across the life span, supports research that 
translates basic genomic science to clinical practice with the goal of 
preventing and alleviating symptoms of chronic illness. Such efforts 
have the potential to improve quality of life for older adults and 
families. Another challenge is Alzheimer's disease (AD), which is 
incurable, affects up to 5.1 million Americans, and is expected to 
dramatically increase in incidence by the year 2030.\3\ NINR is 
addressing the quality of care for AD patients, and the quality of life 
of, and burden on, family caregivers. For example, researchers funded 
by NINR and the National Institute on Aging (NIA) developed an 
intervention to teach caregivers about AD, stress management, and 
maintaining their own health. The intervention showed promising 
improvements in emotional, mental, and physical health in racially 
diverse groups.
---------------------------------------------------------------------------
    \3\ National Institute on Aging. 2009 Progress report on 
Alzheimer's disease: Translating new knowledge.
---------------------------------------------------------------------------
            END OF LIFE: SUPPORTING INDIVIDUALS AND FAMILIES

    As a society we are living longer lives than ever before; however, 
we are also more likely to die from chronic and sometimes painful 
illnesses \4\ that require families to make complex decisions about 
life and death issues, often without adequate support and information. 
As the lead NIH Institute on issues related to end-of-life research, 
NINR supports research leading to evidence-based end-of-life and 
palliative care that ultimately assists individuals, families, and 
healthcare professionals in alleviating symptoms, planning for end-of-
life decisions, and promoting psychological, social, spiritual, and 
physical well-being. NINR's Office of Research on End-of-Life Science 
and Palliative Care, Investigator Training, and Education coordinates 
research, training, and educational efforts in end-of-life and 
palliative care science. One NINR-supported study recently examined the 
effectiveness of a program to communicate patient preferences for end-
of-life decisions to clinicians. Compared to traditional practices such 
as Do-Not-Resuscitate orders, the program led to fewer unwanted life-
sustaining treatments without affecting quality of remaining life. In 
addition, a new NINR initiative begun in 2011 will support research to 
address issues related to end-of-life and palliative care for 
individuals with chronic illness who also experience life-threatening 
acute illness. Finally, on August 10-12, 2011, NINR, with support from 
partners across the NIH, will convene a forum entitled ``The Science of 
Compassion: Future Directions in End-of-Life and Palliative Care.'' 
This forum is intended to energize and mobilize end-of-life and 
palliative care research and to draw attention to the end-of-life and 
palliative care processes, the care options available to patients and 
their families, and the obligations of health service communities to 
address these complex needs.
---------------------------------------------------------------------------
    \4\ Centers for Disease Control and Prevention and The Merck 
Company Foundation. The state of aging and health in America 2007. 
Whitehouse Station, NJ: The Merck Company Foundation; 2007.
---------------------------------------------------------------------------
               TRAINING THE NEXT GENERATION OF SCIENTISTS

    NINR places strong emphasis on equipping the next generation of 
scientists with the necessary skills to conduct research that improves 
the Nation's health. In light of the societal trends that will 
characterize the coming decades, NINR recognizes that tomorrow's nurse 
scientists need to be trained in rigorous, innovative, and 
interdisciplinary research that reaches diverse individuals, families, 
and communities. NINR supports young scientists and junior and senior 
scholars through grant funding, fellowships, and career development 
awards. NINR also offers an intensive summer training program, the 
Summer Genetics Institute, to improve research and clinical practice 
among graduate students and faculty by providing a foundation in 
molecular genetics. Additionally, our Pain Boot Camp, held for the 
first time in 2010, is a 1-week research intensive program where 
participants learn innovative pain research methodology from nationally 
and internationally known scientists. NINR's efforts to invest in new 
investigators and new ideas are critical investments in preparing a 
nursing workforce to address the healthcare challenges of the coming 
years.

                  FUTURE DIRECTIONS IN NURSING SCIENCE

    Nursing science is at the forefront of efforts to improve health 
and healthcare practice. NINR is currently formulating its new 
strategic plan and will continue its focus on the unique social, 
cultural, societal, genetic, and biological factors that contribute to 
disease prevention, health promotion, and self-management of illness. 
We look forward to the next 25 years in which nursing science, focused 
on individuals, patients and families, will make critical contributions 
to improving healthcare practice and quality of life across the disease 
spectrum and across the lifespan. Thank you, Mr. Chairman. I will be 
happy to answer any questions that the Committee might have.
                                 ______
                                 
 Prepared Statement of Donald A.B. Lindberg, M.D., Director, National 
                          Library of Medicine

    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2012 budget request for the National 
Library of Medicine (NLM) of the National Institutes of Health (NIH). 
The fiscal year 2012 NIH request includes $387,153,000 for NLM, which 
is $24,420,000 more than the comparable fiscal year 2011 NLM 
appropriation of $362,733,000.
    As the world's largest biomedical library and the producer of 
internationally trusted electronic information services, NLM delivers 
trillions of bytes of data to millions of users every day. Many who 
begin a search in Google, another search engine, or a mobile ``app'' 
actually receive health information from an NLM website. Now in its 
175th year, NLM is a key link in the chain that makes the results of 
biomedical research--DNA sequences, clinical trials data, toxicology 
and environmental health data, published scientific articles, and 
consumer health information--readily available to scientists, health 
professionals, and the public worldwide. A leader in biomedical 
informatics and information technology, NLM also conducts and supports 
leading-edge informatics research and development in electronic health 
records, clinical decision support, information retrieval, advanced 
imaging, computational biology, telecommunications, and disaster 
response.
    NLM's programs and services directly support NIH's four key 
initiatives. The Library organizes and provides access to massive 
amounts of scientific data from high throughput sequencing; assembles 
data about small molecules to support research and therapeutic 
discovery; provides the world's largest clinical trials registry and 
results database; and is the definitive source of published evidence 
for healthcare decisions. Research supported or conducted by NLM 
underpins today's electronic health record systems. The Library has 
been the principal funder of university-based informatics research 
training for 40 years, supporting the development of today's leaders in 
informatics research and health information technology. NLM's databases 
and its partnership with the Nation's health sciences libraries deliver 
research results wherever they can fuel discovery and support health 
decisionmaking.

                     RESEARCH INFORMATION RESOURCES

    NLM's PubMed/MEDLINE database is the world's gateway to research 
results published in the biomedical literature, linking to full-text 
articles in PubMed Central, including those deposited under the NIH 
Public Access Policy, and on publishers' websites, as well as 
connecting to vast collections of scientific data. Through its National 
Center for Biotechnology Information (NCBI), NLM is a hub for the 
international exchange and use of molecular biology and genomic 
information, with databases accessed by more than 2 million users 
daily. NCBI meets the challenge of organizing, analyzing, and 
disseminating scientific research data with more than 40 integrated 
databases and analysis tools that enable genomic discoveries in the 
21st century. These databases are fundamental to the identification of 
important associations between genes and disease and to the translation 
of new knowledge into better diagnoses and treatments. Resources such 
as dbGAP and the upcoming Genetic Testing Registry (GTR) create a 
bridge between basic research and clinical applications. dbGaP links 
genotype and phenotype information from clinical studies to identify 
genetic factors that influence health and serves as the public 
repository for data from genome wide association studies (GWAS) 
supported by NIH and other research funders. The GTR will be a central 
source for healthcare providers and patients to find detailed 
information about genetic tests and the laboratories that offer them.
    NLM also stands at the center of international exchange of data 
about clinical research studies. NLM's Lister Hill National Center for 
Biomedical Communications builds ClinicalTrials.gov, the world's 
largest clinical trials database, including registration data for more 
than 106,000 clinical studies with sites in 174 countries. 
ClinicalTrials.gov has novel and flexible mechanisms that enable 
submission of summary results data for clinical trials subject to the 
Food and Drug Administration Amendments Act of 2007. To date, summary 
results are available for about 3,400 completed trials of FDA-approved 
drugs, biological products, and devices--providing a new and growing 
source of evidence on efficacy and comparative effectiveness.

          HEALTH DATA STANDARDS AND ELECTRONIC HEALTH RECORDS

    Electronic health records with advanced decision-support 
capabilities and connections to relevant health information will be 
essential to achieving personalized medicine and will help Americans to 
manage their own health. For 40 years, NLM has supported seminal 
research on electronic health records, clinical decision support, and 
health information exchange, including concepts and methods now used by 
MicroSoft Health Vault and Google Health. As the central coordinating 
body for clinical terminology standards within HHS, NLM works closely 
with the Office of the National Coordinator for Health Information 
Technology (ONC) to facilitate adoption and ``meaningful use'' of 
electronic health records (EHRs). NLM supports, develops, and 
disseminates key data standards for U.S. health information exchange in 
ONC's criteria for certification of electronic health records. NLM is 
actively engaged in research on Next Generation EHRs, while also 
developing tools and frequently used subsets of large terminologies to 
help EHR developers and users implement health data standards right 
now. Most recently, NLM released MedlinePlus Connect, which allows 
application developers to establish direct links from a patient's view 
of his or her EHR to high quality health information relevant to that 
person's specific health conditions, medications, and (coming soon) 
recent tests.

                  INFORMATION SERVICES FOR THE PUBLIC

    This new EHR connection builds upon NLM's extensive information 
services for patients, families and the public. The Library's 
MedlinePlus website provides integrated access to high quality consumer 
health information produced by all NIH components and HHS agencies, 
other Federal departments, and authoritative private organizations and 
serves as a gateway to specialized NLM information sources for 
consumers, such as the Genetic Home Reference and the Household 
Products database. Available in English and Spanish, with selected 
information in 40 other languages, MedlinePlus averages well over 
600,000 visits per day. Covering nearly 900 health topics, MedlinePlus 
has interactive tutorials for persons with low literacy, an illustrated 
medical encyclopedia, surgical videos and links to the scientific 
literature in PubMed. Mobile MedlinePlus, also in both English and 
Spanish, reaches the large and rapidly growing mobile Internet 
audience.
    The NIH MedlinePlus quarterly magazine is an outreach effort made 
possible with support from many parts of NIH and the Friends of the 
NLM. Like MedlinePlus itself, the magazine is free and contains no 
advertising. It is distributed to the public via physician offices, 
community health centers, libraries and other locations and has a 
readership of up to 5 million nationwide. Each issue focuses on the 
latest research results, clinical trials and new or updated guidelines 
from the 27 NIH Institutes and Centers. A Spanish/English version, NIH 
MedlinePlus Salud, launched with support from the National Alliance for 
Hispanic Health and the National Hispanic Medical Association, 
addresses the specific health needs of the growing Hispanic population 
and showcases the many Hispanic outreach efforts and relevant research 
results funded by the NIH.
    To be of greatest use to the widest audience, NLM's information 
services must be known and readily accessible. The Library's outreach 
program, with a special emphasis on reaching underserved populations, 
relies heavily on the more than 6,300-member National Network of 
Libraries of Medicine (NN/LM). The NN/LM is a network of academic 
health sciences libraries, hospital libraries, public libraries and 
community-based organizations working to bring the message about NLM's 
free, high-quality health information resources to communities across 
the Nation.

                    DISASTER INFORMATION MANAGEMENT

    Events of the past year, such as the Deepwater Horizon oil spill 
and the earthquake, tsunami, and radiation event in Japan, demonstrated 
yet again the importance of rapid, organized response to natural 
disasters and other emergencies. NLM has a long history of providing 
health information to prepare for, respond to, and recover from 
disasters and has tools and advanced information services designed for 
use by emergency planners, responders and managers. Through its 
Disaster Information Management Resource Center, NLM builds on proven 
emergency backup and response mechanisms within the National Network of 
Libraries of Medicine to promote effective use of libraries and 
disaster information specialists in disaster preparedness and response. 
NLM also conducts research on new methods for sharing health 
information in emergencies as its contribution to the Bethesda Hospital 
Emergency Preparedness Partnership, a model of private-public hospital 
collaboration for coordinated disaster planning. NLM partners with the 
Pan American Health Organization (PAHO) and other bodies in the Latin 
American Network for Disaster and Health Information to promote 
capacity-building in the area of disaster information management.
    Within 2 days of the gulf oil spill, NLM launched a web page 
focused on the potential effects of oil on human health, which quickly 
became a highly regarded resource for evidence-based information by 
Federal, State, and local agencies and communities. NLM continued to 
support information needs in Haiti, including onsite assistance to PAHO 
in setting up a system for collecting information from cholera 
treatment centers. The Radiation Emergency Medical Management (REMM) 
tool, previously developed by NLM, the HHS Office of the Assistant 
Secretary for Preparedness and Response, CDC and NCI, was deployed in 
Japan, via the web and on mobile devices, to assist with assessing and 
managing the health effects of radiation. NLM also activated the 
Emergency Access Initiative, a partnership with publishers and medical 
libraries which provides free temporary access to key electronic 
medical journals and books when disasters interrupt regular health 
information services, and provided practical advice to Japanese 
libraries and archives on rescuing water-damaged books and documents.
    In summary, NLM's information services and research programs serve 
the Nation and the world by supporting scientific discovery, clinical 
research, education, healthcare delivery, public health response, and 
the empowerment of people to improve personal health. The Library is 
committed to the innovative use of computing and communications to 
enhance public access to the results of biomedical research.
                                 ______
                                 
  Prepared Statement of Jack Whitescarver, Ph.D., Director, Office of 
                             AIDS Research

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2012 President's budget request for the trans-NIH AIDS 
research program, which is $3,159,531,000. This amount is an increase 
of $100,254,000 over the fiscal year 2011 enacted level. It includes 
the total NIH funding for research on HIV/AIDS and the wide spectrum of 
AIDS-associated malignancies, opportunistic infections, co-infections, 
and clinical complications; intramural and extramural research; 
research management support; research centers; and training. It also 
includes a transfer of approximately $27 million to the HHS Office of 
the Assistant Secretary of Health to foster collaborations across HHS 
agencies and finance high priority initiatives in support of the 
President's National HIV/AIDS Strategy.

                           THE AIDS PANDEMIC

    Nearly 30 years since the recognition of AIDS and the 
identification of HIV as its causative agent, the HIV/AIDS pandemic 
remains a global scourge. UNAIDS reports that in 2009, more than 33 
million people were estimated to be living with HIV/AIDS; 2.6 million 
were newly infected; and 1.8 million people died of AIDS-related 
illnesses. The majority of cases worldwide are the result of 
heterosexual transmission, and women represent more than 50 percent of 
HIV infections worldwide. More than 1,000 children become infected each 
day, most of them as newborns. More than 25 million men, women, and 
children worldwide have already died.
    In the United States, CDC reports that more than 1.1 million people 
are estimated to be HIV-infected; approximately 56,300 new infections 
occur each year; and someone is infected with HIV every 9\1/2\ minutes. 
HIV/AIDS continues to be an unrelenting public health crisis, 
disproportionately affecting racial and ethnic populations, women of 
color, young adults, and men who have sex with men. The number of 
individuals aged 50 years and older living with HIV/AIDS is increasing, 
due in part to antiretroviral therapy, which has made it possible for 
many HIV-infected persons to live longer, but also due to new 
infections in individuals over the age of 50.

                       NIH AIDS RESEARCH PROGRAM

    To address this pandemic, NIH has established the most significant 
AIDS research program in the world, a comprehensive program of basic, 
clinical, translational, and behavioral research in domestic and 
international settings--a multi-disciplinary, global research program 
carried out by every NIH institute and center in accordance with their 
mission. This diverse research portfolio requires an unprecedented 
level of trans-NIH planning, scientific priority-setting, and resource 
management. The Office of AIDS Research (OAR) was authorized to plan, 
coordinate, evaluate, and budget all NIH AIDS research, functioning as 
an ``institute without walls,'' to identify the highest priority areas 
of scientific opportunity, enhance collaboration, minimize duplication, 
and ensure that precious research dollars are invested effectively and 
efficiently.

               NEW SCIENTIFIC ADVANCES AND OPPORTUNITIES

    The past year has been a significant one for AIDS research. The NIH 
investment in the priority areas of HIV prevention research and in 
basic science over the past several years has resulted in important 
progress in critical areas of the NIH AIDS research program. Recent 
research advances by NIH intramural and extramural investigators have 
opened doors for new and exciting research opportunities in the search 
for strategies to prevent, treat, and ultimately cure HIV infection. 
These advances include:
    Technologies to accelerate discovery--
  --Vaccines.--A team of scientists led by researchers at the NIAID 
        Vaccine Research Center discovered two potent human antibodies 
        that can stop more than 90 percent of known global HIV strains 
        from infecting human cells in the laboratory and determined the 
        structural analysis of how they work. The novel techniques used 
        in this research may accelerate HIV vaccine research as well as 
        the development of vaccines for other infectious diseases. An 
        HIV vaccine clinical trial conducted in Thailand by NIH and the 
        Department of Defense demonstrated the first indication of a 
        modest but positive effect in preventing HIV infection. The 
        trial marked the first step in proving the concept that a 
        vaccine to prevent HIV infection is feasible.
  --Microbicides.--For the first time in nearly 15 years of research, 
        scientists discovered a vaginal microbicide gel that gives 
        women a level of protection against HIV infection. The study, 
        sponsored by USAID and conducted by the Centre for the AIDS 
        Programme of Research in South Africa (CAPRISA), found that the 
        use of a microbicide gel containing the antiretroviral drug 
        tenofovir resulted in 39 percent fewer HIV infections compared 
        with a placebo gel. NIH provided substantial support and 
        resources to establish the infrastructure and training for 
        CAPRISA. Ongoing and future NIH clinical trials will build on 
        these study results with the goal of bringing a safe and 
        effective microbicide to licensure.
  --Basic Science.--This past year, using genome-wide association 
        studies, NIH-sponsored researchers made an important discovery 
        related to the genetics of an individual's immune system. These 
        genes appear to be involved in the control of HIV disease 
        progression among a group of individuals considered ``elite 
        controllers,'' who have been exposed to HIV over an extended 
        period, but whose immune systems have controlled the infection 
        without therapy and without symptoms. These findings will 
        contribute to the development of potential HIV prevention 
        strategies.
    Translational sciences and therapeutic development.--New lymphoma 
regimens have been developed that can be tailored to specific tumor 
types. This development has markedly improved the therapeutic outcome 
and survival of patients with AIDS-related lymphoma. In addition, 
progress in both basic science and treatment research aimed at 
eliminating viral reservoirs has been significant enough that 
scientists are now, for the first time, planning to conduct research 
aimed at a cure. NIH has announced several initiatives to generate new 
ideas for curing HIV infection through domestic and international 
partnerships among government, industry, and academia.
    Enhancement of evidence-base for healthcare decisions.--In the 
critical area of treatment as prevention, two recent studies have 
demonstrated the effectiveness of new multi-drug antiretroviral 
regimens for the prevention of mother-to-child-transmission of HIV 
during pregnancy and breastfeeding. In addition, a large international 
NIH clinical trial provided strong evidence that the use of pre-
exposure prophylaxis (PrEP), that is, the use of antiretroviral 
treatment before exposure to prevent infection, can reduce risk of HIV 
acquisition in men who have sex with men. Additional and continued 
research is needed to determine whether PrEP will be similarly 
effective at preventing HIV infection in other at-risk populations and 
assist healthcare workers in providing these potential options.

                       TRANS-NIH PLAN AND BUDGET

    These advances, while preliminary and incremental, provide the 
groundwork for further scientific investigation and the building blocks 
for the development of the trans-NIH AIDS strategic Plan, developed by 
OAR in collaboration with both government and non-government experts. 
The priorities of the strategic Plan guide the development of the 
trans-NIH AIDS research budget. OAR develops each IC's AIDS research 
allocation based on the Plan, scientific opportunities, and the IC's 
capacity to absorb and expend resources for the most meritorious 
science--not on a formula. This process reduces redundancy, promotes 
harmonization, and assures cross-Institute collaboration. The 
priorities of the Plan will establish the biomedical and behavioral 
research foundation necessary to implement the major goals of the 
President's National HIV/AIDS Strategy and to implement the NIH 
Director's themes.

                 FISCAL YEAR 2012 SCIENTIFIC PRIORITIES

    A growing proportion of patients receiving long-term antiretroviral 
therapy (ART) are demonstrating treatment failure, experiencing serious 
drug toxicities and side effects, and developing drug resistance. 
Recent studies have shown an increased incidence of malignancies, as 
well as cardiovascular and metabolic complications, and premature aging 
associated with long-term HIV disease and ART. NIH research will 
address the need to develop better, less toxic treatments and to 
investigate how genetic determinants, sex, gender, race, age, pregnancy 
status, nutritional status, and other factors interact to affect 
treatment success or failure and/or disease progression.
    NIH-funded research is needed to address the causes of HIV-related 
health disparities, their role in disease transmission and acquisition, 
and their impact on treatment access and effectiveness. These include 
disparities among racial and ethnic populations in the United States; 
between developed and resource-constrained nations; between men and 
women; between youth and older individuals; and disparities based on 
sexual identity. In addition, specific fiscal year 2012 research 
priorities include: biomedical and behavioral research focused on the 
domestic AIDS epidemic, particularly in racial and ethnic populations 
of the United States; research to build on important research advances 
in prevention research in the past year in the areas of microbicides, 
vaccines, and treatment as prevention; research to prevent and treat 
HIV-associated co-morbidities, malignancies, and clinical 
complications; research to address the complex issues around AIDS and 
aging; research to better understand the issues of adolescents and 
AIDS; basic and therapeutic research focused on elimination of viral 
reservoirs leading toward a cure; genetic studies to delineate the 
genetic basis for immune responses to HIV and to sequence HIV-
associated tumors; and research on feasibility, effectiveness, and 
sustainability required for the scale-up and implementation of 
interventions in communities at risk.

                                SUMMARY

    The OAR has utilized its authorities to shift AIDS research program 
priorities and resources to meet the changing epidemic and scientific 
opportunities. This investment in AIDS research has produced 
groundbreaking scientific advances. AIDS research also is helping to 
unravel the mysteries surrounding many other cardiovascular, malignant, 
neurologic, autoimmune, metabolic, and infectious diseases as well as 
the complex issues of aging and dementia. Despite these advances, 
however, AIDS has not been conquered, and serious challenges lie ahead. 
The HIV/AIDS pandemic will remain the most serious public health crisis 
of our time until better, more effective, and affordable prevention and 
treatment regimens are developed and universally available. NIH will 
continue its efforts to prevent, treat, and eventually cure AIDS.
    Thank you for your continuing support for our efforts.
                                 ______
                                 
   Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D., Principal 
             Deputy Director, National Institutes of Health

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2012 President's budget request for the Office of the 
Director (OD). The fiscal year 2012 budget includes $1,298,412,000; an 
increase of $132,451,000 over the comparable fiscal year 2011 enacted 
level of $1,165,961,000, comparable for transfers proposed in the 
President's request.
    The OD promotes and fosters NIH research and research training 
efforts in the prevention and treatment of disease through the 
oversight of the Intramural Research program and through coordination 
of program offices responsible for stimulating specific areas of 
research throughout NIH to complement the ongoing efforts of the 
Institutes and Centers. The OD also develops policies in response to 
emerging scientific opportunities employing ethical and legal 
considerations; maintains peer review policies; provides oversight of 
grant and contract award functions; coordinates information technology 
across the Agency; and coordinates the communication of health 
information to the public and scientific community. Moreover, the OD 
provides the core management and administrative services, such as 
budget and financial management, personnel, property, and procurement 
services, ethics oversight, and the administration of equal employment 
policies and practices.
    The principal OD offices providing these activities include the 
Offices of Extramural Research, Intramural Research, Science Policy, 
Communications and Public Liaison, Legislative Policy and Analysis, 
Equal Opportunity and Diversity Management, Financial Management, 
Budget, Management, Human Resources, Chief Information Office, and the 
Executive Office. This request contains funds to support the functions 
of these offices as will be outlined in the Program, Project and 
Activities Table which follows.
    The statement is submitted with the recognition of the Department's 
notification to the Congress of an NIH reorganization that would 
establish a new National Center for Advancing Translational Sciences 
and reallocate the remaining portions of the National Center for 
Research Resources to other parts of NIH, including the OD.

 DIVISION OF PROGRAM COORDINATION, PLANNING, AND STRATEGIC INITIATIVES 
                                (DPCPSI)

    The DPCPSI mission includes identifying the most compelling 
scientific opportunities, emerging public health challenges, and 
scientific knowledge gaps that merit further research or would 
otherwise benefit from strategic coordination and planning across the 
Agency. DPCPSI provides key support of research that is consistent with 
the NIH Director's Themes. The Division is comprised of the Office of 
AIDS Research, Office of Research on Women's Health, Office of 
Behavioral and Social Sciences Research, Office of Disease Prevention, 
Office of Medical Applications of Research, Office of Dietary 
Supplements, Office of Rare Diseases Research, and the Office of 
Strategic Coordination (OSC). The OSC is responsible for the oversight 
and management of the NIH Common Fund. The Division is responsible for 
agency-wide effort in portfolio analysis and also manages NIH-wide 
evaluation and performance activities, including the Evaluation Set-
Aside program and the Government Performance and Results Act plans and 
reports. The fiscal year 2012 budget for DPCPSI/Office of the Director 
is $8,401,000. Descriptions of the eight programmatic offices within 
DPCPSI, and their separate budgets, follow.

                      THE OFFICE OF AIDS RESEARCH

    The Office of AIDS Research (OAR) plays a unique role at NIH, 
establishing a plan for the AIDS research program. OAR coordinates the 
scientific, budgetary, legislative, and policy elements of the NIH AIDS 
research program. OAR's response to the AIDS epidemic requires a unique 
and complex multi-institute, multi-disciplinary, global research 
program. This diverse research portfolio demands an unprecedented level 
of scientific coordination and management of research funds to identify 
the highest priority areas of scientific opportunity, enhance 
collaboration, minimize duplication, and ensure that precious research 
dollars are invested effectively and efficiently, allowing NIH to 
pursue a united research front against the global AIDS epidemic. The 
fiscal year 2012 budget for OAR is $65,760,000.

                THE OFFICE OF RESEARCH ON WOMEN'S HEALTH

    The Office of Research on Women's Health (ORWH) mission is to 
enhance and expand research supported by the NIH to adequately address 
women's health. This is done by identifying gaps in knowledge, and 
collaborating with the ICs to stimulate and support innovative research 
including interdisciplinary scientific approaches to women's health and 
studies of sex and gender differences in health and diseases. ORWH 
continues to lead efforts to ensure adherence to policies for the 
inclusion of women and minorities in clinical research The fiscal year 
2012 budget for ORWH is $43,811,000.

         THE OFFICE OF BEHAVIORAL AND SOCIAL SCIENCES RESEARCH

    The Office of Behavioral and Social Sciences Research (OBSSR) was 
established by Congress to stimulate behavioral and social science 
research at NIH and to integrate it more fully into the NIH research 
enterprise. The Office furthers the NIH mission by emphasizing the 
critical role that behavioral and social factors play in health, 
healthcare, and well-being. The Office supports the activities of the 
NIH Basic Behavioral and Social Science Opportunity Network, a trans-
NIH initiative to expand the agency's funding of basic behavioral and 
social sciences research. The fiscal year 2012 budget for OBSSR is 
$27,949,000.

                    THE OFFICE OF DISEASE PREVENTION

    The primary mission of the Office of Disease Prevention (ODP) is to 
stimulate disease prevention research across the NIH and to coordinate 
and collaborate on related activities with other Federal agencies as 
well as the private sector. The fiscal year 2012 budget for ODP is 
$1,400,000. The Office of Medical Applications of Research (OMAR), 
Office of Dietary Supplements (ODS), and Office of Rare Diseases 
Research (ORDR) are within the ODP organizational structure.
    The Office of Medical Applications of Research (OMAR) mission is to 
work with NIH Institutes, Centers, and Offices to assess, translate and 
disseminate the results of biomedical research that can be used in the 
delivery of important health interventions to the public. The fiscal 
year 2012 budget for OMAR is $4,877,000.
    The Office of Dietary Supplements (ODS) promotes study of the use 
of dietary supplements by supporting investigator-initiated research, 
and through other major mechanisms. The fiscal year 2012 budget for ODS 
is $28,691,000.
    The Office of Rare Diseases Research (ORDR) supports activities 
that stimulate research on rare diseases by collaborating with the 
research institutes, research investigators, patient advocacy groups, 
the pharmaceutical industry, and Federal regulatory and research 
agencies. The fiscal year 2012 budget for ORDR is $18,423,000.

        THE OFFICE OF STRATEGIC COORDINATION AND THE COMMON FUND

    The Office of Strategic Coordination (OSC) facilitates strategic 
planning and management of Common Fund-supported programs by working 
with groups of staff from across the NIH to develop and implement each 
individual program while providing central management for the Common 
Fund as a whole. The NIH Common Fund was enacted into law by Congress 
through the 2006 NIH Reform Act to support cross-cutting, trans-NIH 
programs that require participation by at least two NIH Institutes or 
Centers (ICs) or would otherwise benefit from strategic planning and 
coordination. The Common Fund provides limited-term funding for new 
programs that are intended to catalyze research in the ICs through the 
development of cross-cutting resources, technologies, and data sets. 
Common Fund programs do not address any particular disease or 
condition, but rather, are designed to be broadly relevant. The fiscal 
year 2012 budget for the Common Fund is $556,890,000.

                    THE OFFICE OF SCIENCE EDUCATION

    The Office of Science Education (OSE) develops science education 
programs, instructional materials, and career resources that serve our 
Nation's science teachers, their students (kindergarten through 
college), and the public. OSE's activities are an important component 
to the overall Agency effort to achieve the NIH Director's goal to 
reinvigorate and empower the biomedical research community and enhance 
America's competitiveness in the global economy. The OSE creates 
programs to improve science education in schools (the NIH Curriculum 
Supplement Series) that stimulate interest in health and medical 
science careers (LifeWorks Web site); and advance public understanding 
of medical science, research, and careers; and advises NIH leadership 
about science education issues. The OSE website is a central source of 
information about available education resources and programs. http://
science.education.nih.gov. The fiscal year 2012 budget for OSE is 
$4,120,000.

                LOAN REPAYMENT AND SCHOLARSHIP PROGRAMS

    The Office of Intramural Training and Education administers the NIH 
Intramural Loan Repayment and Undergraduate Scholarship Programs 
(UGSP). The Loan Repayment Programs (LRPs) seek to recruit and retain 
highly qualified physicians, dentists, and other health professionals 
with doctoral-level degrees. These programs offer financial incentives 
and other benefits to attract highly qualified physicians, nurses, and 
scientists into careers in biomedical, behavioral, and clinical 
research as employees of the NIH. The NIH UGSP offers competitive 
scholarships to exceptional college students from disadvantaged 
backgrounds that are committed to biomedical, behavioral, and social 
science health-related research careers at the NIH. The fiscal year 
2012 budget is $7,653,000 for the Intramural Loan Repayment and 
Undergraduate Scholarship Programs.
    I am happy to answer any questions you may have about the OD's 
programs and activities as well as our plans for the upcoming year.
                                 ______
                                 
    Prepared Statement of Jeremy M. Berg, Ph.D., Director, National 
                 Institute of General Medical Sciences

    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2012 President's budget request for the National 
Institute of General Medical Sciences (NIGMS). The fiscal year 2012 
budget request includes $2,102,300,000, an increase of $70,263,000 
above the fiscal year 2011 appropriation of $2,032,037,000, which has 
been adjusted comparably to reflect NIH proposed transfers. This 
statement is submitted with the recognition of the Department's 
notification to the Congress of an NIH reorganization that would 
establish a new National Center for Advancing Translational Sciences 
and reallocate the remaining portions of the National Center for 
Research Resources to other parts of NIH.
    Since the mid-20th century, NIGMS has played a leading role as 
NIH's ``basic research institute.'' Spanning a broad spectrum, the 
Institute's mission supports discovery ranging from how cells work to 
how diseases affect communities across towns, nations, and countries. 
NIGMS-supported scientists probe the unknown to solve mysteries about 
fundamental life processes. This effort goes well beyond the need to 
satisfy innate curiosity; answering basic research questions such as 
how bacterial and human cells divide, move, and communicate has 
increased our knowledge about infections, cancer, birth defects, and 
heart disease in ways that would have been difficult to achieve with 
more directed studies. Other ongoing NIGMS research investments, such 
as in chemistry, continue to provide tangible benefits to society and 
our economy. This past year, an NIGMS-supported scientist shared a 
Nobel Prize for his discovery of a ground-breaking chemistry method 
that is used routinely in the pharmaceutical, electronic and 
agricultural industries.
    Continued investment in basic research is vital because many of 
today's therapies, although effective, nevertheless have significant 
limitations. Treatments that are applied after the onset of serious 
illness--kidney transplants and dialysis, bypass surgery for coronary 
artery disease, surgical removal of tumors--though often lifesaving, 
are still not optimal. Treating disease before such interventions are 
needed would likely improve both outcomes and quality of life. Basic 
biomedical and behavioral research has the power to move treatments in 
this direction, and in the coming years, emerging biotechnology and 
nanotechnology tools will give researchers unprecedented precision to 
detect and derail disease at its earliest stages.

                  TECHNOLOGIES TO ACCELERATE DISCOVERY

    Basic research on stem cells remains one of the most rapidly 
advancing areas of biomedicine, in large part because of the knowledge 
base scientists already have about how cells behave and change. NIGMS-
supported research on stem cells continues to provide hope that these 
multitalented cells will find use in customized therapies for a range 
of conditions. In the near term, stem cells are providing researchers 
powerful tools for understanding diseases and developing drugs to treat 
them. This past year, NIGMS-funded researchers made important progress 
on several fronts:
  --Stem cell research pioneer James Thomson, D.V.M., Ph.D., created a 
        powerful tool to trace the individual steps in a deadly cancer 
        by turning the clock back on blood cells from a person with 
        leukemia.
  --Chemist Laura Kiessling, Ph.D., developed an inexpensive and simple 
        synthetic culture system for growing embryonic stem cells in 
        the laboratory.
  --NIH Director's New Innovator Awardee Alysson Muotri, Ph.D., used 
        cells from a person with Rett syndrome to create a cellular 
        model of autism.
    Another area showing great promise is molecular diagnosis. This 
past year, NIH Director's Pioneer Awardee Thomas Kodadek, Ph.D., 
applied a unique and creative strategy that conducts an ``immune 
surveillance'' of human blood to look for early signs of disease before 
symptoms appear. To date, he has obtained exciting evidence that 
Alzheimer's disease may be detectable by this approach, and he has 
licensed the technology to further its development and application.
    The study of systems--of cells, organs, and diseases--is an 
important area of basic discovery within the NIGMS mission. In 2010, 
the Institute grew its support of systems biology by adding two new 
National Centers for Systems Biology. All 12 centers integrate 
approaches from engineering, genomics, and systems and synthetic 
biology to identify principles and architectural features involved in 
common cellular behaviors, including the response to disease-causing 
microorganisms, poisons, and metabolic imbalances.
    Computer modeling is a key element of all systems biology, and a 
central aspect of the NIGMS-led Models of Infectious Disease Agent 
Study (MIDAS). This international effort continues to add new research 
expertise to increase its capacity to simulate disease spread, evaluate 
different intervention strategies, and help inform public health 
officials and policymakers. This past year, two MIDAS findings are 
worth highlighting:
  --One MIDAS study used computer modeling to analyze the spread of 
        H1N1 flu in a Pennsylvania elementary school. The researchers 
        collected extensive data from seating charts, school 
        timetables, bus schedules, nurse logs, attendance records and 
        questionnaires. The findings indicated that transmission occurs 
        mostly through girl-to-girl and boy-to-boy interactions and 
        that sitting directly next to a child with the flu does not 
        raise a child's risk of getting it.
  --In another MIDAS study, researchers learned that the Haiti cholera 
        outbreak that followed that Nation's colossal earthquake in 
        2010 could have been blunted with the use of a mobile stockpile 
        of oral cholera vaccine.

          TRANSLATIONAL SCIENCES AND THERAPEUTICS DEVELOPMENT

    Since the landmark discovery of the structure of DNA in the 1950s, 
our increasing knowledge of how all living things share a basic set of 
working parts has catalyzed progress in biomedicine. Large-scale 
efforts to scan and compare genomes are teaching scientists about 
individual differences in DNA scripts that predispose us to disease. 
However, such sequence information is only useful if it can be properly 
interpreted. NIGMS has been at the forefront of supporting research 
that facilitates this interpretation, leading to numerous discoveries 
that have revealed new, unforeseen mechanisms by which DNA information 
is made operational.
    As one example, the NIGMS Protein Structure Initiative (PSI) has 
been creating knowledge and providing tools to researchers for more 
than 10 years. This past year, NIGMS enhanced this signature effort by 
launching PSI:Biology, a new program that supports research 
partnerships between groups of biologists and high-throughput structure 
determination centers to solve medically important problems. Already 
this investment is bearing fruit, yielding new structures that show how 
the largest class of drug receptors functions.
    Another example is a pilot study by an individual scientist that 
searched systematically for environmental factors--nutrients, chemicals 
and toxins--that may be linked to diabetes. Based conceptually on the 
Genome-Wide Association Studies approach, Atul Butte, M.D., Ph.D., 
developed a new technique he calls Environment-Wide Association 
Studies. In this method, he considered many different factors at once, 
using health survey data from the U.S. Centers for Disease Control and 
Prevention, which led him to identify 266 environmental factors linked 
to type 2 diabetes. This example highlights the tremendous potential 
benefits of integrating existing data sources and asking the right 
questions.

         ENHANCEMENT OF EVIDENCE BASE FOR HEALTHCARE DECISIONS

    Although medicines have been revolutionary in humankind's ability 
to stay healthy, we now know that people having widely varying 
responses to the drugs they take to heal their various ills. NIGMS has 
been a long-time supporter of pharmacogenomics, the study of how our 
DNA influences the way we respond to medications. This area of research 
is an especially important focus in our country today, as the baby-boom 
generation gets older and is more likely to take multiple medicines 
routinely. NIGMS leads the trans-NIH Pharmacogenomics Research Network 
(PGRN), a nationwide collaborative of scientists looking for clues to 
inherited variability in the response to medicines used to treat heart 
disease, asthma, cancer, depression and addiction.
    This past year, two new groups joined the network, adding 
rheumatoid arthritis and bipolar disorder as new focus areas. Over the 
next 5 years, the PGRN plans to expand to pursue cutting-edge DNA 
sequencing methods and statistical analysis, as well as to perform 
pilot studies to learn about medication response from de-identified 
medical records in healthcare systems. Furthermore, previous PGRN-based 
discoveries are now moving further into clinical application with 
evidence accumulating on improved outcomes and lower costs.

                      NEW INVESTIGATORS, NEW IDEAS

    Biomedical and behavioral research is a human endeavor, and NIGMS 
has a long-standing commitment to supporting and sustaining the people 
behind the research. Creativity comes from the sparks of individual 
minds, and thus the Institute has always adhered to the principle that 
a healthy workforce is an essential ingredient for good science that 
leads to better health for all.
    Science and the conduct of research continue to evolve, though, as 
do workforce needs. It is our responsibility to stay attuned to these 
new needs and opportunities. In 2010, NIGMS launched a process to 
examine its activities and general philosophy of research training--to 
assure that all of the Institute's activities related to the training 
of scientists are aligned with our commitment to build an excellent, 
diverse research workforce to help achieve the NIH mission, now and in 
the long term.
    NIGMS gathered data and input from the scientific community through 
a series of regional meetings across the country, as well as through 
other means of electronic communication including a webinar, online 
postings, and comment submissions via e-mail. The resulting plan, 
Investing in the Future, the NIGMS Strategic Plan for Biomedical and 
Behavioral Research Training, was released in early 2011.
    A key focus of this plan is the importance of putting the needs of 
trainees first--by focusing on mentoring, career guidance, and 
diversity. The plan also affirms the Institute's strong assertion that 
there are multiple avenues in which a well-trained scientist can make 
meaningful contributions to society. These include research careers in 
academia, Government, or the private sector, as well as careers 
centered on teaching, science policy, patent law, communicating science 
to the public, and other areas.
    In closing, and on the cusp of my departure from Federal service, I 
want to note how proud I have been to play a role in furthering the 
basic research that has had such a profound effect on the health and 
well-being of our Nation. I will treasure the time and effort spent 
leading the fine institution that is NIGMS.

                AVERAGE COST OF RESEARCH PROJECT GRANTS

    Senator Harkin. Well, thank you, Dr. Collins. Very poignant 
ending for your testimony.
    We will now begin a round of 5-minute questions.
    Dr. Collins, in addition to drastically cutting NIH 
funding, the House Appropriations bill would have required NIH 
to fund a minimum number of new competing research grants and 
put a ceiling on the average cost to them.
    I have a letter here from a number of different entities--
American Association for Cancer Research, American Medical 
Colleges, American University--a whole list of different people 
who've written us a letter saying that this would really hamper 
the ability of NIH to fund the best, the most innovative, the 
brightest by putting a cap on it. Now, you have to fund so many 
and you have to--I think it was 9,000--and then they put a cap 
on it of, I think, $400,000, if I'm not mistaken.
    Again, I'd like you to speak to that. We've been down this 
road before over the last 25 or 30 years that I've been on this 
subcommittee, in saying that NIH really ought to do this on a 
peer-reviewed basis. Some of the projects cost more, some cost 
less, but to limit it and then to say you have to do so many, 
takes away the ability to really do a good peer-reviewed 
systematic approach to this.
    I would like you to respond to that and what that would 
mean to NIH if, in fact, we were to set a limit on how much and 
to mandate that you have to fund at least so many grants.
    Dr. Collins. Senator, I appreciate the question. This is a 
very serious issue and you've set it up quite well in terms of 
what the risks might he here.
    Certainly, that feature of the language that was part of 
H.R. 1 was deeply troubling to those of us at NIH, because, as 
you have just said, the goal of all of us who tried to carry 
out our responsibilities to support the very best biomedical 
research is to utilize the tools of peer review, to seek advice 
from the scientific community and our advisory councils about 
how best to utilize the resources that the taxpayers, through 
this Congress gives to us.
    The idea that we would have to manage that enterprise in an 
arbitrary way to try to hit a certain number of grants, and 
particularly to try to hit some average cost of a new and 
competing grant could potentially seriously interfere with the 
flexibility that we believe is necessary for the best science 
to be supported.
    For instance, clinical trials tend to be more expensive. 
Would this kind of a limit on the average costs of a new and 
competing grant find its way into conversations about, well, 
maybe we should do fewer clinical trials and more grants that 
happen to be inexpensive, like conference grants? That would 
be, I think, a serious intrusion into the ways in which, 
really, scientific decisions should be made.
    So I agree with you that that particular kind of way of 
tying NIH's hands would be very unfortunate. Given all of the 
scientific opportunities that we have right now, we should be 
able to pursue them in a way that represents the best decisions 
and not managed in this sort of arbitrary way by trying to hit 
certain numerical grant limits.

                                DIABETES

    Senator Harkin. I appreciate that.
    Dr. Rodgers, on diabetes, I think we saw that chart there 
about moderate changes in diet and exercise resulting in a huge 
decrease in the incidence of the disease. I had 71 percent and 
the chart said 58 percent, so I have to figure out why there's 
a difference here. When you testified a few years ago on this, 
you said you would be undertaking a follow-up study to see 
whether these could be sustained over time. What's happened?
    Dr. Rodgers. That's correct, Senator, and thanks for the 
question.
    First of all, the 71 percent, even though the average 
improvement in terms of a reduction with that intensive 
lifestyle modification was 58 percent for all comers, among the 
people over 60 years of age, it was 71 percent. So they really 
enjoyed the best benefit of all of the subsets of the patients 
studied.
    Now, the initial trial, the diabetes prevention trial, was 
published in 2002, and, at that point, the reduction was 58 
percent for intensive lifestyle, 31 percent for a drug, 
metformin.
    But, more recently, the 10-year follow-up, which is what I 
was referring to at that hearing, was just published in the 
Lancet in 2009, and that shows, as Dr. Collins mentioned, a 
durable effect out 10 years. These patients who engaged in the 
intensive lifestyle still showed a reduction of their going on 
to develop diabetes, and the patients, in fact, who were on the 
metformin also continued to show an improvement.
    Senator Harkin. Very good.
    Now, my 5 minutes is up, but I have other questions for 
other people here. I'll do that on my second round.
    Senator Shelby.

                         NCATS BUDGET AMENDMENT

    Senator Shelby. Thank you, Mr. Chairman.
    Dr. Collins, I'm going to get back into NCATS for a minute. 
I think it's very important, and I think it has great promise.
    I think that NCATS proposal requires thoughtful 
consideration to the effect that it will have on NIH, the 
extramural research community and the private pharmaceutical 
market. You've alluded to this a little.
    As I stated, I remain concerned that this announcement was 
made in December, yet we don't have some details before the 
subcommittee yet.
    The reorganization will impact all of NIH's 27 Institutes 
and Centers and will shift at least $1.3 billion. I believe the 
subcommittee needs to review such a proposal, especially one 
that has such a potential impact on the NIH community.
    My question is when will we receive some more details that 
we can renew--for the staff and the subcommittee--or do you 
have a timeline? I know it's a difficult transition.
    Dr. Collins. Senator, it's a very fair question, and I had 
certainly hoped that by the time of this hearing we would have 
been able to provide the full details about the budgetary 
consequences of standing up this new and exciting new center.
    It is a complicated process. The recommendation to do this 
came forward from my Scientific Management Review Board last 
December 7.
    Rather than putting this off until fiscal year 2013, which 
I thought would really have wasted an opportunity, we decided 
we would try to move as quickly as possible. Although some 
people said, ``Hey, this is the Government. You can't possibly 
do that by October'', well, they used to say that about the 
Genome Project. So I decided that we could, and we should, 
because this is the best way to move the science forward.
    But, of course, what this means is taking a number of 
components that already exist in various institutes and in the 
common funded NIH and moving them together into this new 
synergistic entity. That's important to point out.
    Actually, what we're talking about is not to create new 
budgetary implications, with the one exception of the Cures 
Acceleration Network, which is in the President's fiscal year 
2012 budget at $100 million, and which we hope this 
subcommittee and others will see fit to support, because it'll 
give us some flexibilities in terms of how we manage the budget 
that we would dearly love to have.
    But the other pieces of NCATS are basically derived from 
existing programs that are moved together in a way that are 
going to be highly complementary and synergistic.
    We needed, of course, to consult with our communities, with 
our constituencies, and, as we figured out how to do the 
shifting right down to every employee to make sure that the 
programs were encouraged and nurtured, we had to be sure we had 
that right.
    We are at the point now where we believe we have that 
together. It needs, of course, to be reviewed by the Department 
of Health and Human Services (HHS) and Office of Management and 
Budget (OMB) experts. We hope to get that to you, Senator, in 
the fairly near future, within, certainly, the next few weeks 
and, hopefully, a very few weeks.

                   COST OF DE-RISKING PHARMACEUTICALS

    Senator Shelby. Dr. Collins, you've also described the 
NCATS mission as one of what you call de-risk--that moves basic 
scientific discoveries beyond the lab to a point where the 
private pharmaceutical market feels confident enough to jump 
in.
    What is the policy or what would you think the policy would 
be if a selected project is successfully de-risked, but no 
companies produce the drug or medical product? I know you've 
thought about that.
    Dr. Collins. And, indeed, I should point out that this is 
an activity which NIH has been engaged in for some long periods 
of time, and my colleagues, particularly from the National 
Cancer Institute (NCI) and National Institute of Allergy and 
Infectious Diseases (NIAID), have been supporting this kind of 
translational effort in always looking for a commercial partner 
at the earliest moment in order to be able to carry a project 
through to completion and limit the amount of dollars that the 
taxpayers have to cover.
    I would say projects that get undertaken at this point need 
to think about that from the very beginning. There will be 
instances perhaps where no commercial partner can be found, 
even all the way through to the end of a phase III trial, but 
they will be rare indeed, because those are very expensive 
enterprises.
    But for very rare diseases, where the economic incentives 
are simply going to be very limited, and especially if one is 
in a circumstance where you could conduct such a clinical trial 
by repurposing a drug that's already been approved for 
something else, then NIH may very well find it worthwhile to 
undertake that effort.
    But you're quite right to point this out. We have to get 
the balance----

                    HEALTH PREPAREDNESS AND OBESITY

    Senator Shelby. Absolutely.
    Just want to touch on health disparities. You got into it a 
little. Health disparities most often associated with the ethic 
population persist in rural United States. Stroke, diabetes, 
kidney disease and cancer are all more prevalent in both the 
African-American community as well as the South.
    One of the root causes to health disparity is the obesity 
epidemic that is rampant in our Nation. You pointed it out in 
your slides. Southern States have the highest rates in the 
Nation.
    My question is should we be looking for a new paradigm that 
broadly addresses this critical national issue at multiple 
levels for molecules to behavior to policy? You touched on it 
with your slide. And how can NIH help the American people meet 
that challenge?
    Dr. Collins. So, Senator, I really appreciate the question 
because this is an enormous public-health challenge for all 
communities, but particularly so for certain underserved 
communities.
    I'm going to turn to my colleagues, Dr. Rodgers and Dr. 
Shurin, who lead the Obesity Task Force at NIH, who are just 
putting forward a new research plan that's quite exciting.
    Dr. Rodgers. Thank you, Senator.
    Because of the extreme importance of this project, and 
particularly the recognition that obesity is occurring much 
more frequently in children in this country, we've also asked 
Dr. Collins for his permission to have the Director of the 
Child Health Institute on board as a co-chair of this obesity 
research task force.
    As Dr. Collins indicated, we just put out this last month a 
strategic plan which highlights a blueprint for research in 
these critical areas related to prevention and potential 
treatment of obesity, particularly in health disparities or in 
certain ethnic and racial groups, in older adults, in young 
children.
    And it recognizes the fact that obesity is a multifaceted 
problem, and, therefore, you need multifaceted solutions, 
including behavioral, medical, surgical and others.
    Senator Shelby. How important is behavioral here----
    Dr. Rodgers. Behavioral research is extremely important. 
For example, we know that for childhood obesity just decreasing 
screen time, the amount of time kids are in front of the 
television, the computer, video games can greatly reduce the 
risk. Increasing physical activity is another important 
component to this.
    Let me turn to my colleague, Dr. Shurin, who actually has a 
very active program involving children.
    Dr. Shurin. Thank you, Senator. We share your very deep 
concerns about this.
    One of the things that Dr. Rodgers and I have done is to 
convene a group, a collaborative on obesity with the CDC and 
the Department of Agriculture with the support of the Robert 
Wood Johnson Foundation, which has a particular interest in 
childhood obesity.
    So we have a multifaceted research program. Much of it is 
community-based research, but it also ties in to many 
biologically and behaviorally oriented research programs really 
looking at the factors that impact obesity.
    As Dr. Rodgers has said, we've got several studies now 
which show a very profound influence of screen time. Physical 
activity is at least as important as diet, but dietary issues 
are obviously of major importance. And we have a very rich 
portfolio of research projects looking at what are the most 
effective interventional strategies.
    Many of these are site-based, worksite-based and school-
based programs. I think one of the things that's particularly 
important is that many of the projects that we get into which 
look very promising don't actually pan out. It's very helpful 
for us to know what doesn't work, so we can really be fairly 
aggressive in pursuing the ones that do.
    The impact of policy changes, the engagement of the food 
industry and of preventive health services we think are 
particularly important. We initiated a program called We Can, 
which is ways of enhancing childhood activity and nutrition, 
which we have now several thousand community partners aimed 
very heavily at reducing screen time and increasing physical 
activity and focusing very heavily on dietary activities.
    We have several collaborations with the food industry, with 
several partners in the food industry which have become 
increasingly responsive, but we think that there are probably 
going to have to be some policy approaches that will have an 
impact on this, that simply relying on individual choices is 
not going to be sufficient.
    Senator Shelby. Thank you. Thank you, Mr. Chairman.
    Senator Harkin. Thank you. In keeping with the 
subcommittee's policy in order of appearance here at the 
subcommittee be Senator Reed, Senator Moran, Senator Mikulski, 
Senator Brown.
    Senator Reed.

                         GLOBAL COMPETITIVENESS

    Senator Reed. Thank you very much, Mr. Chairman, and thank 
you, doctors.
    Dr. Collins, just a quick point, that Chinese facility that 
you mentioned to is supported by the Chinese Government or do 
we know?
    Dr. Collins. Interesting. It is partly supported by the 
Government, but they actually have put this in place by taking 
out a bank-supported loan to allow them to purchase 128 of 
these----
    Senator Mikulski. They didn't get it here.
    Dr. Collins. Senator Mikulski is correct. It was not at an 
American bank. And they have purchased 128 of these sequencing 
machines, the largest collection in the world, and they are 
quite confident that the value economically will fully justify 
the cost of buying the machines.
    They've also hired about 4,000 of the smartest young 
scientists that I've ever seen in one place from all over China 
who are in their 20s and who are prepared to change the world 
and probably are going to.
    And we should celebrate that. I don't mean in any way to 
say I think this is a bad thing, but it worries me to see that 
China has taken that kind of initiative and we have not.
    Senator Reed. But the financing might be considered quasi 
private and public together, but this is clearly an initiative 
at the highest levels of the Chinese Government to get this 
done.
    Dr. Collins. Yes.
    Senator Reed. And we are at this debate here in the United 
States about what we will commit as a Government to not only 
the genome sequencing, but so many of the innovative proposals 
you've talked about.
    Dr. Collins. That's correct----

                      NIC VOLKER TREATMENT DETAILS

    Senator Reed. Just want to clarify that.
    I thought also, joining the chairman, that the poignant 
story of Nic--I wonder did he or his doctors avail themselves 
to the National Cord Blood Registry, CDC's the MATCH? Was that 
a----
    Dr. Collins. I don't know in terms of where his stem cell 
transplant came from. I can find that out for you, Senator.

                           PEDIATRIC RESEARCH

    Senator Reed. But that's an initiative that Senator Hatch 
and I worked on and I hope it contributed to that great story.
    [The information follows:]
                Nic and the National Blood Cord Registry
    David A. Margolis, M.D., professor of pediatrics and director of 
the Bone Marrow Transplant Program at the Children's Hospital of 
Wisconsin, said, ``Our donor coordinator says `Yes. If it were not for 
the National Marrow Donor Program, and the single access that it 
provides, the search (for Nic's cord blood stem cell donor) would have 
been more difficult, time consuming, and may not have yielded the same 
results.' ''

    Senator Reed. But this raises a larger question, then, in 
terms--that I have with respect to the amount of resources 
going to pediatric research. You've cited several examples. Dr. 
Rodgers, Dr. Shurin have talked about, you know, the research 
you're doing in children's obesity, et cetera.
    For example, I'm told that only about 4 percent of the 
funds in the National Cancer Institute are for pediatric 
cancers. That might be good news, because it might represent 
that it's a relatively healthy population, but just generally a 
sense do you think we're making the right allocation of 
resources to pediatric research?
    If we're not, are there structural issues; that is, is the 
peer-based review tilted toward adult experts rather than 
pediatric experts? Any comments I'd appreciate.
    Dr. Collins. Well, quickly, and then I'll ask Dr. Varmus to 
address the pediatric oncology issue, but we have an entire 
Institute at NIH, the National Institute of Child Health and 
Human Development, which has as its major focus pediatric 
research and which certainly is a place of a great deal of 
interest and excitement right now because there are so many 
promising developments in childhood illness.
    We also are investing in a very large national project, an 
unprecedented one, the National Children's Study, which will 
enroll 100,000 kids beginning even before conception through 
pregnancy and up to age 21 in order to comprehensively collect 
the kind of information about environmental exposures and 
genetics that may shed light on diseases like autism and 
diabetes that have continued to vex us.
    I would say, yes, there's a lot of investment. Could there 
be more? You bet there could, but that would probably be true 
in virtually every area that we're looking at. With these 17 to 
18 percent success rates that were mentioned by the chairman, 
we are clearly not able to support a lot of great science that 
we'd like to support.
    Senator Reed. Before Dr. Varmus, I must say that Brown 
University Medical School is participating along with Women and 
Infants Hospital, and Dr. Rodgers is their commencement 
speaker, because he's one of the most illustrious Brown 
University medical graduates in the history of the program. I 
had to put that in the record. Forgive me, Dr. Collins.
    Dr. Varmus.
    Dr. Varmus. Senator Reed, thank you very much, and I 
appreciate your honoring my colleague, Dr. Rodgers.
    You're correct that the amount of money we specifically 
identify as being devoted to pediatric cancer research is about 
4 percent of our budget, which is about $200 million a year, 
but, of course, a great deal of other funding that we're 
involved in addresses cancer more generally and is applicable 
to pediatric problems.
    Let me say a few words more broadly about pediatric cancer. 
Chairman Harkin alluded to the fact that we do cure most 
patients with leukemia. Pediatric cancers, in general, are much 
more effectively treated, whether they're brain tumors or 
neuroblastomas or Wilms tumor or leukemias, but, nevertheless, 
there still is an increased incidence of childhood cancers over 
the last several years by about 30 percent, but a continuing 
decline in mortality.
    Nevertheless, mortality figures do not tell us the whole 
story. There are severe consequences of being treated for 
cancer at an early age--developmental defects, loss of mental 
capacity in some individuals, and, of course, a very high 
incidence of second tumors, particularly in survivors' 20s and 
30s.
    We're trying to address these problems in a variety of 
ways. We're trying to understand the cancers more profoundly 
with some of the genomic-sequencing techniques that Dr. Collins 
alluded to.
    We, in fact, have spent Recovery Act money on a new project 
to study pediatric cancers in great detail. And we have new 
therapeutic maneuvers that are based on more targeted, bullet-
specific drugs and antibodies that have been very effective in 
reducing mortality rates in neuroblastoma and leukemias with 
therapies that are less toxic.
    We have paid a lot of attention to the survivors of 
pediatric cancer. We have a nationwide survivors study for 
pediatric cancer that has enrolled over 20,000 patients in 
roughly 37 different centers. So with these and other projects, 
we think we're making a pretty good effort to control the 
consequences of treatment of pediatric cancer and to do a 
better job in treating pediatric cancers in a less toxic 
manner.
    But you're correct, we could do more, but, as you know, we 
have budget constraints this year. It's unlikely that we'll see 
a very significant increase in that domain or any other in the 
coming year.

              BIOMEDICAL RESEARCH RESOURCES AND WORKFORCE

    Senator Reed. Thank you very much. Thank you, gentlemen. 
Thank you, Dr. Shurin. Thank you, Mr. Chairman.
    Senator Moran. Chairman Harkin, thank you.
    Dr. Collins and your colleagues, fellow doctors, I 
appreciate the opportunity to have this conversation with you 
this morning.
    This is a beginning course for me. I have 4 months of being 
a United States Senator and being a member of this 
subcommittee, but I'm excited about joining Senator Harkin and 
Senator Shelby and my colleagues here.
    I think medical research is a huge component of the future 
of our country. I think it matters greatly, and I commend you 
for your efforts to date.
    In my healthcare reform bill, we would support medical 
research in a dramatic way. I think it's a cost-saving measure. 
It's about saving people's lives, improving the quality of 
their life. And so from an economic--as you point out--but also 
from a personal, humanitarian point of view, what we do here in 
this subcommittee and what you do at NIH matters greatly.
    And I would welcome the opportunity to become better 
acquainted with NIH, its personnel, its mission. Maybe the 
people in the rows behind you--I want my doctors out there 
doing the research, but I'm happy to have others at NIH devote 
some time to educating me so that I can better understand how 
we can advance the cause of medical research here in the United 
States.
    I would ask first if there is something missing. We're here 
in an appropriations subcommittee, but other than money, is 
there something missing at NIH or here in our country, in the 
United States, that makes it much more difficult or makes it 
difficult for you to reach the goals that you outlined for us 
today or is this just a financial issue, how many dollars do we 
devote? What are the other, if any, impediments toward success?
    Dr. Collins. Well, Senator, I appreciate the question and 
certainly appreciate your strong statement of support, and you 
are most welcome to come and visit us at NIH. We'd love to host 
you for a visit and show you some of the things that are going 
on in the laboratories and in the clinical center, the largest 
research hospital in the world, that's up there in Bethesda.
    Senator Moran. Thank you.
    Dr. Collins. But as you know, most of the money that NIH 
sends out in grants goes to the 50 States, including Kansas, 
and we're very proud of the research that's going on there in 
your State.
    Senator Moran. Thank you.
    Dr. Collins. In terms of other things that potentially are 
barriers, certainly we do not have what I would call a vigorous 
pipeline of young scientists coming into our field, and part of 
that is the sad state of K through 12 science education in this 
country, which has certainly, by any measure, slipped badly 
over where it used to be back in the--30 or 40 years ago in the 
sort of post-Sputnik arena where science education was really 
emphasized.
    Now, in many schools, it is unfortunately quite 
rudimentary, and I think we lose, therefore, the chance to 
capture young people's imagination that science would be a 
place they wanted to spend their own careers. And that means we 
have fewer American-born individuals who are clamoring to come 
in to our laboratories and make the next great discoveries.
    We have lots of interest from individuals born in other 
countries to do that, but that interest has actually declined a 
bit as more opportunities are present in their own countries.
    Some of them, certainly in large numbers, still come to 
train in our universities, but they often now go back to their 
original homes and carry out research instead of staying in the 
United States. And some of our visa practices have not helped 
in that regard in terms of making such talented scientists from 
other countries feel less welcome than we wish they were.
    It seems to me that would be a very important area for us 
to, again, try to get right, because it is to our advantage to 
recruit such individuals--and our universities are still seen 
as the very best in the world--to come and do their research, 
but then for us to also be able to capture their talents in an 
ongoing way I think would be a great advantage. That is just 
one of the areas.
    But, frankly, the major concern that I think we have is 
just the lack of sufficient resources to chase down all of the 
great ideas that are now potentially possible.

                       INTERDISCIPLINARY RESEARCH

    Senator Moran. I appreciate that answer and look forward to 
finding solutions in that regard and understand now the 
importance you place upon the resources.
    I did visit the University of Kansas last week and one of 
the research facilities there, the Molecular Libraries Program, 
and I'm very interested in what the ranking member pursued in 
regard to NCATS.
    And when I heard your testimony today, my assumption is 
that this will take a lot of different kinds of scientists 
engaged in this effort, and I guess an initial question would 
be what steps would you anticipate being taken to ensure that 
the best of American science in as many areas will have that 
opportunity to contribute to this new program?
    Dr. Collins. Well, a very appropriate point. It will take 
an interdisciplinary effort of a considerably revolutionary 
sort.
    It means bringing together biologists and chemists--as no 
doubt you saw at the Molecular Libraries Program in Kansas--
along with computational experts, structural biologists who can 
actually figure out the shape of molecules and figure out which 
shapes fit together in a way that might make a particular drug 
work, immunologists who can help us with monoclonal antibody 
development, engineers who can work on devices that will be the 
next generation of what we need for all manner of medical 
applications, and those disciplines traditionally haven't had 
such an easy time talking to each other, and one of our goals 
through this program and many others is to do that.
    Maybe this is also partly in answer to your first question 
about what are some of the barriers. In some way our own 
traditional disciplines have presented some of that problem, 
although I think those barriers are coming down.
    Clearly, there's a lot of excitement--and I suspect you 
perceived that in your visit to the Kansas center--about the 
potential here of bringing those disciplines together with 
these new comprehensive sciences to enable academic 
investigators to play a larger role in reengineering this 
broken pipeline to try to make it possible to come up with 
therapeutics and devices and diagnostics in a shorter time 
period.
    This resonates with me for the same kind of feeling I had 
about the Genome Project 20 years ago. It was controversial 
then, too, of course. A lot of people wondered whether this was 
biting off more than the Government could chew, but it 
recruited into the effort some of the best and brightest minds 
of that generation because they could see the potential.
    I think that same atmosphere is beginning to appear in 
translational science, and I suspect once we have the programs 
in place it will not be hard to recruit some really brilliant 
minds to play a role in this.
    Harold, did you want to add to that?
    Dr. Varmus. I think it might be important to reassure you, 
Mr. Moran, about the effort that's being made in translational 
research across the institutes.
    As Francis alluded to in his testimony, a great deal of 
work--interdisciplinary work, indeed--has gone on in the 
Institutes and will continue to go on, while NCATS provides a 
catalytic advantage to the efforts that we're making by 
providing new methodologies, ways to analyze how translational 
research is done, some core facilities.
    But, as you probably know from going to your cancer center 
at the University of Kansas, that there is a lot of 
translational research going on there, and that's done by 
interdisciplinary teams.
    So all of us at the NIH are engaged in this process and 
we've had a lot of experience in gathering multidisciplinary 
teams over the last decade or so to do this kind of work.
    Senator Moran. So it's not new and we know it can be done. 
It's being done today.
    Dr. Varmus. But we're all engaged in the process, and it's 
not going to fall solely on the head of NCATS.
    Senator Moran. And, unfortunately, I'm on the social 
science in my education and I detect that the same thing may be 
there between chemistry and biology as there is between history 
and political science.
    Dr. Varmus. Well, there could well be. Yes----
    Senator Moran. But I appreciate that, and I did see the 
enthusiasm. That was perhaps the takeaway of my visit is the 
excitement that is there and the belief in the potential of 
what can be accomplished.
    Dr. Varmus. Yes.
    Senator Moran. It's very appealing to me.
    Dr. Collins. Dr. Fauci wants to add something.
    Dr. Fauci. There is one other thing that sometimes gets 
misunderstood. We mention--and Dr. Varmus mentioned also that 
there's a lot of translational research going on.
    What the center is going to be directing itself at is to 
really advance what we call the discipline of translational 
research, in other words, to help us to do more innovative ways 
of approaching translational research. So translational 
research goes on to the tune of many billions of dollars at the 
NIH, mostly in the big Institutes, but some of the smaller 
Institutes also.
    What we want to do is advance the discipline of how it's 
done, making it a 21st century approach toward translational 
research as opposed to relying on many of the methodologies 
that have been good, but that we think we can do better on. 
That's what it's really all about, putting forth the discipline 
and improving the discipline of translational research.
    Senator Harkin. Thank you. Thank you, Senator Moran.
    Senator Mikulski.

                             SUPPORT OF NIH

    Senator Mikulski. Thank you very much, Mr. Chairman. I'm 
very proud of the fact that NIH is located in the State of 
Maryland. And for more than 25 years, I've visited NIH 
regularly, and every time I come, my eyes pop with wonder, my 
heart beats with excitement and I just--one of the reasons I 
wanted to be here today was to tell you and all of the people 
who work at NIH how proud I am of you, and how America ought to 
be proud of you.
    Dr. Collins, you did path-breaking pioneering work when 
mapping the genome. And we were in a race. You had another 
competitor down the street. You broke the code and we 
invented--not only mapped the code, but came up with new fields 
called computational biology, bioinformatics, new exciting 
careers that help both us in particularly the private sector be 
able to come up with new products.
    And, Dr. Fauci, you, what you've done. You were the guy who 
broke the AIDS code. You were the guy that came here when we 
were gripped in fear and near panic when we were shut down due 
to anthrax and we had no place to turn in our United States 
Government for information, but we turned to you and you kept 
us on the right path, so that we could keep the doors of the 
Capitol----
    Dr. Varmus, a former head of NIH. You know, NIH Directors 
don't leave. They leave legacies, and then they come back to 
create new ones, and we're so glad to see you. And we note that 
when you were at Sloan-Kettering you had a lot of other zeros 
behind your compensation package, which says something about 
why you came back.
    And to Dr. Rodgers and Dr. Shurin, who also was educated at 
Hopkins, we're just glad to see you.
    And, Mr. Chairman, and what they do is the work that helps 
us manage the biggest budget busters in our healthcare budget--
diabetes, heart disease, the chronic conditions that lead to 
chronic problems in the way we live, in the way we have to fund 
healthcare.
    So I wanted to be here today to say for all the people work 
at the institutes, all the people work at the various offices, 
all the lab techs, the security guards, the fire department, 
we're really proud of you.
    So having said that, I want to make sure we help NIH be 
NIH. So I want to stick to the basic mission in addition to 
these exciting new ideas.
    Dr. Collins, how many research grants did NIH fund last 
year, and how many requests did you get for funding? In other 
words, what is the funding gap, and particularly not only with 
the tried and true research, but also with those promising 
young, maybe more upstart type thinking?
    Dr. Collins. So in fiscal year 2010, we funded 
approximately 9,300 research grants. The success rate in fiscal 
year 2010 came out at just about 20 percent; that is, one out 
of five that were able to be supported.
    With the fiscal year 2011 budget now in front of us, now 
that it's been decided, we won't do that well, because, of 
course, as you know, after the dust all settled, we ended up 
with a 1-percent cut of $320 million, although I really want to 
express my appreciation----
    Senator Mikulski. So that's what one percent means, $320 
million?
    Dr. Collins. That's correct. But I do want to express my 
appreciation to members of this subcommittee, because I know 
there was a great deal of debate about exactly where the dust 
would all settle out, and certainly many of the proposals were 
vastly worse than this, and I know many people really went to 
bat for NIH, and we appreciate that enormously.
    But we do believe that in fiscal year 2011--with some 
uncertainty in the number, because we don't actually know how 
many grants we will receive, and, of course, we're talking 
about a proportionality here--that the success rate will fall 
to approximately 17 to 18 percent, and that will be the lowest 
in history.
    We will do our best to try to manage the resources that 
we've got, and we've made a number of adjustments to try to 
keep that number----
    Senator Mikulski. But for every one grant that you can 
fund, let's even go to before fiscal 2011, how many are 
unfunded?
    Dr. Collins. So it would be five out of the six. If you 
have six grants in front of you, we're going to fund one of 
them and five of them are going to go begging.

                           WORKFORCE PIPELINE

    Senator Mikulski. All of which are quite promising.
    Now, let's go to much is made about recruiting young people 
into science, and we want a lot of initiatives in that, but 
young people follow opportunity. So when we look at your 
internship, your fellowship program, both for high school, 
undergraduates and so on, again, how many students can you have 
come in to NIH? And how many--In other words, how many can you 
take and how many apply? What's the enthusiasm gap here?
    Dr. Collins. Well, there is enormous enthusiasm. Certainly, 
we run a number of internship programs on the NIH campus. We 
have a program for high school students and college students 
who come and spend 10 weeks in the summer. That is always 
oversubscribed by at least a factor of five in terms of the 
number of slots that we have available and the space that's in 
the labs.
    We also have a program for individuals who are finishing 
college, who are really interested in science, but they're not 
sure whether they want to go to graduate school or medical 
school. They come and spend 1 year, sometimes 2 years doing 
full-time research in the lab.
    I have three of those students in my lab right now. They're 
enormously energized, excited about what they're doing, and 
they go on to do great things. This is a really important 
program.
    But there again, the number of applications we have for 
that so-called post bac program is at least four or five times 
greater than the number of slots that we have available to 
offer.
    Senator Mikulski. So while we're busy--You know, we like to 
pound our chest and come up with all kinds of things in 
education to encourage people for science, but our young people 
are going in it, but they need opportunity, both in the public 
as well as in the private sector.
    Dr. Collins. So, Senator, I've just set up, as part of my 
advisory committee to the Director, a working group to look at 
our workforce issues, and I've asked Dr. Shirley Tilghman, the 
president of Princeton, to co-chair that, because I think we 
need a better handle on what the supply-and-demand issues are 
in terms of the biomedical research workforce.
    We want to be sure that we're looking forward with a clear 
eye toward all of the different pathways that are going to need 
well-trained, doctoral-level biomedical researchers and that 
we, NIH, as a major source of training support are 
appropriately tuning our programs so that we have the numbers 
right in terms of how many people we are bringing in and what 
kinds of careers we're preparing them for.

                    EFFECTS OF A GOVERNMENT SHUTDOWN

    Senator Mikulski. Well, I think this would be enormously 
useful to this subcommittee, Mr. Chairman, because, as you 
know, this is a topic--a big public-policy topic they ponder 
all of the time.
    My last just comment or question is with all the talk of 
the shutdown and during H.R. 1, a cut to the National Cancer 
Institute, which was stunning to many people, including me, 
what is the morale at NIH now that they thought that they might 
be sent home and told that they were non-essential and the cuts 
might be coming?
    I mean, I must say both the chairman and the ranking member 
were enormously supported to minimize the disaster, but it was 
not a victory.
    Dr. Collins. So I would say this was a very difficult 
period to go through. We were required, of course, in 
preparation for what appeared to be a very high likelihood of a 
shutdown, to define how we would manage that, and that meant 
defining which particular employees were considered essential 
and which were excepted, was the term that was used, and which 
were non-excepted.
    And, of course, those who were involved in patient care or 
management of animals couldn't very well just not come to work, 
but others were told, ``I'm sorry. If there is a shutdown, you 
can't come to work.''
    Think about how that feels if you're a post-doctoral fellow 
who's in the middle of an experiment that you've been working 
on for 2 or 3 weeks and has another couple of weeks to go and 
you're being told, ``I'm sorry. You're not allowed to come to 
work tomorrow if the Government shuts down.'' It did have a 
very significant effect. People were quite shaken up by that.
    I think people are--in the aftermath of that--feeling a 
little uncertain about what it's like to work in this 
environment and hoping that we won't face that again. But, 
again, I think everybody understands these are terribly, 
terribly difficult times for our country.

                 INFLATION EFFECTS ON PURCHASING POWER

    I just want to show you one image because I think it might 
be actually useful.
    [The information follows:]

    
    

    Senator Mikulski. Okay. I'm going to just--chairman 
regulate the time, but I'm fine with it, but if that's okay 
with the chairman.
    Dr. Collins. It'll take 1 second. This is basically why we 
are in such a crunch.
    Senator Mikulski. Well this is a terrific slide.
    Dr. Collins. So this is--this shows----
    Senator Mikulski. It's more like the way my heart went up 
during the shutdown mode.
    Dr. Collins. So in blue, you see the appropriations for NIH 
going back to 1998. You see the doubling that happened between 
1998 and 2003, and then you see that since 2003 the NIH budget 
has been much more in a flat trajectory.
    But in yellow, you see the effects of inflation, the 
biomedical research and development index, which has been 
eating away at our buying power since 2003, placing us now, 
even with the President's budget, in the range of what we were 
at 2001. So we're sort of where we were 10 years ago.
    You see the Recovery Act dollars there in 2009 and 2010, 
which were a wonderful boost to the scientific community, but, 
of course, that was 2-year money.
    That is why the success rates are now dropping to where 
they are. It's all pretty much clear what the consequences 
would be once one considers what's happened to buying power for 
research.
    Senator Mikulski. Thank you. Mr. Chairman, thank you.
    Senator Harkin. Senator Mikulski.
    Senator Mikulski. You are the genius club. I mean, you 
really are. So thank you.
    Dr. Collins. Thanks.
    Senator Harkin. Senator Brown.

                           NEW INVESTIGATORS

    Senator Brown. Thank you, Mr. Chairman. And I've always so 
enjoyed having panels from NIH, some of the smartest people in 
the country, especially those who used to teach in Cleveland, 
Dr. Shurin.
    But thank you. I mean, it really is illuminating and we 
thank you so much for your service. This is such an example of 
public service and why government matters.
    And when I hear some of the know-nothings that hold jobs 
like we hold say that the Government is broke and that 
Government can't function and Government doesn't contribute 
anything and Government doesn't create jobs, you know, I think 
about the special forces. Those were Government employees that 
were in Abbottabad, but I think primarily of what NIH does and 
what you contribute to public health and to wealth of our 
country.
    I want to take up on what Senator Mikulski said, and Dr. 
Collins' response, on the one out of five grants. I was in the 
House, ranking Democrat on the subcommittee back when we 
actually wanted to fund public health bipartisanly in this 
country 15 years ago, doubled the budget at NIH.
    And I remember in those days those numbers that some of 
your predecessors--well, some of you and some of your 
predecessors--would cite, now that we fund one out of five 
grants or one out of six grants. It's gotten a bit worse than 
what Senator Mikulski said.
    The other part of that story that I remember is the young 
researchers that you are always looking to attract when you 
teach at med schools and you counsel people and you mentor 
people, those are the least likely to be the one out of five 
that gets the grants--or the one out of six--because my 
understanding is that people that have done these grants over 
time kind of know how to win the grants better than the young, 
bright researcher also applying for the grant. So the numbers, 
in some sense, among younger, hungry researchers are even 
worse, the ratios, and too many of these young people leave the 
field.
    And I think that's, to me, the most compelling reason that 
this fervor to cut budgets as--we need to address our budget 
deficit, but we're creating terrible deficits in young 
scientists and terrible deficits in the public body of 
knowledge, I just want to say.

                        COST OF PHARMACEUTICALS

    Let me go--two issues I want to talk briefly about. One is 
the issue of the Makena drug, the progesterone that was 
developed over time into a--produced by compounding pharmacies 
as you know, has made a huge difference, provable huge 
difference, clinically trialed--if that's a verb or adverb--
huge difference in preventing early birth, pre-term births.
    We know what this KV Pharmaceuticals in St. Louis did. We 
also know that you at NIH have invested $21 million on now four 
clinical trials, in the midst of the fourth one and still 
investing in this and finding, I think, more indications, 
perhaps, to use this drug, this progesterone, this compounded 
pharmacy drug.
    Well, just give me your thoughts, briefly, if you would, 
how do we prevent this from happening? The Food and Drug 
Administration (FDA) has stepped in and done something pretty 
unusual and pretty gutsy by saying they're not going to enforce 
the cease-and-desist order on compounding pharmacies.
    So when I talk to obgyns and visit hospitals--I was at 
University Hospitals yesterday in Cleveland--2 days ago--
talking about they're still compounding it, still producing 
this.
    When taxpayers invest in this and it's clearly a drug in 
the public interest and one company can get exclusivity for 7 
years, while you continue to do these clinical trials 
expanding--in a sense expanding their market on this fourth 
clinical trial you're doing--and I know this cuts across FDA, 
HHS as a whole and you and CDC and all, but what do we do about 
this?
    Dr. Collins. Well, Senator, I think you spoke out quite 
strongly about the Makena situation and I think brought a lot 
of attention to a circumstance that really was deeply 
troubling, that a drug--let's just call it 17P--that was 
previously available and compounded by pharmacists and then was 
put into a clinical trial, ultimately ended up, after FDA 
approval and orphan-drug status, going up in cost from 
something that cost $10 or $20 to something that costs $1,500.
    We were also deeply alarmed to see that and quite pleased 
to see FDA step in and say they were not going to go after 
pharmacists that continued to provide the compounded material.
    And that, by the way, also, and along with your strong 
statements and that from some of the professional groups, did 
cause KV Pharmaceuticals to drop their costs, but still at a 
much higher level than they were in the old days.
    NIH has its hands a bit tied in this situation. Back in the 
1990s, when Harold Varmus was NIH Director, we had a big 
discussion about whether drugs that NIH plays a role in 
developing should have some sort of reasonable pricing clause 
attached to any kind of licensing that we would do to a 
company.
    And while that might have seemed like a way to avoid 
another kind of Makena outcome, it was a poison pill for any 
serious relationship that NIH would have with a company. No 
company in this country or elsewhere would be interested in a 
partnership with NIH under those circumstances.
    What we can do is to make sure that if profits ensue and 
NIH has made a contribution to that, in terms of genuine 
intellectual property discoveries, that there should be royalty 
sharing on that basis.
    But when it comes to setting the price, as KV did, even 
though we supported the clinical research, we are probably not 
the agency in a position to be able to do something to step in 
and interfere with their pricing decision.
    It was the public outcry, your outcry, Representative 
DeLauro, the professional societies that I think actually 
turned the tide.
    Senator Brown. But that outcry only brought the price from 
$1,500 multiplied times 20, with 20 weeks of treatment, as you 
know----
    Dr. Collins. Yes.
    Senator Brown [continuing]. $1,500, $30,000, when it was 20 
times $10 or $20--depending on the compounded pharmacy's 
charge--down to $690. So the outcry worked with FDA. The outcry 
barely worked with KV.
    But is there a way to sort of cross the--I understand that 
you don't want to engage in partnering and price-setting and 
all that, but--or maybe you do--but when a company so 
overreaches like this, it was such an affront to the public 
interest, if there's a way, sort of across help agencies we 
could find some solutions or----
    I mean, Dr. Hamburg was in here and she said, well, you 
know, FDA didn't do this. She wasn't defensive at all, but then 
FDA did something. This was before they made that decision.
    But I just will follow up with you, but I'd like to see if 
there's a way to----

                            CANCER CLUSTERS

    My other question--I'm sorry to go over the 5 minutes, Mr. 
Chairman--Dr. Varmus, you had talked about pediatric cancers 
and Senator Reed had asked you about that.
    There's a cancer cluster in Clyde, Ohio, where many, many 
children, under 12 in most cases, have developed cancer, and I 
know you see these. There are four or five believed to be 
cancer clusters. I don't know if that's a particular medical 
term, but is certainly what we talk about.
    What is NIH's role in sort of examining these, exploring 
these, finding out the environmental cause, if it is that, as I 
presume--I guess I presume it is. What is your role in that?
    Dr. Varmus. Well, we do investigate that. We have a 
Division of Epidemiological Cancer Research that will look at 
these clusters to ascertain whether or not the cluster is real. 
Because, as you might expect, if cancers are distributed in 
their frequency across the country, there are going to be some 
places that just, by chance, have a particularly high or 
particularly low incidence, and there are several classical 
examples of clusters that turned out only to be arithmetic 
aberrations, but without any clear indication of causes.
    On the other hand, there have been clusters of cancers that 
are linked to certain practices or to exposure to industrial 
mutagens, and we would go in with collaboration with the 
National Institute of Environmental Health Sciences and try to 
ascertain what might be a precipitating cause.
    So we do have a role and we would--I don't know about the 
one you're citing, but we can certainly look into it and report 
back to you on what----
    Senator Brown. We have talked to NIH overall, but we will 
specifically talk to you.
    Thank you, Mr. Chairman.
    [The information follows:]

                       Clyde, Ohio Cancer Cluster

    State and Federal Responses to Cancer Cluster Reports.--State and 
local health departments respond to cancer cluster reports and provide 
the first level of response and review of the most current local data 
for the area. If needed, these local health departments can request 
assistance from Federal agencies, including the National Center for 
Chronic Disease Prevention and Health Promotion (NCCDPHP) of the 
Centers for Disease Control and Prevention (CDC), the Agency for Toxic 
Substances and Disease Registry (ATSDR), and the U.S. Environmental 
Protection Agency (EPA). CDC's role in investigating potential cancer 
clusters is to provide technical assistance to States at their request 
as they conduct their investigations. In State cancer registries, 
States have the data needed to determine whether a cluster exists.
    National Cancer Institute (NCI).--NCI does not investigate 
anecdotal clusters of individual cancer cases in neighborhoods, but 
rather clusters of counties with elevated rates as part of the 
geographic mapping strategy to identify and investigate high-risk 
populations for etiologic insights. However, upon occasion NCI's 
Division of Cancer Epidemiology and Genetics (DCEG) may be called upon 
to consult with local and State health officials and CDC experts as 
they investigate purported cancer clusters.
    DCEG's research portfolio includes analysis of cancer treands in 
human populations, and DCEG investigators conduct studies both within 
the U.S. and around the world where the incidence of certain cancers is 
significantly higher than might be expected. Examples of such 
investigations include lung cancer in coastal communities in the U.S., 
which was linked to asbestos exposure in ship yards, and oral cancer in 
women in the rural south, which was linked to smokeless tobacco use. 
DCEG researchers are currently investigating the reasons for the very 
high rates of bladder cancer in northern New England; they will soon be 
reporting data from this effort. They are also conducting a study to 
explore the elevated rates of Burkitt's lymphoma in regions in Africa.
    Regarding the Clyde, Ohio Investigations.--It is our understanding 
that there was a multi-year analysis of a suspected cancer cluster in 
Clyde, Ohio by the Ohio Department of Health (ODH). Both CDC and ATSDR 
provided technical assistance to the State officials over the course of 
the multi-year assessment. While NCI has not received any reports or 
conclusions, it is our understanding that the assessment's final 
conclusion was that the data were inconclusive and there was no cancer 
cluster identified. These Federal public health agencies are continuing 
their collaboration with ODH and are available to provide support as 
needed.

                              FLU VACCINE

    Senator Harkin. Thank you, Senator Brown.
    Dr. Fauci, for years, you've been here, year after year, 
and we've talked about flu vaccines, and, some time ago, I 
remember you talked about progress being made toward a--perhaps 
a universal type flu vaccine. You mentioned it in your written 
statement, which I read last night. Again, how close are we?
    Dr. Fauci. Well, I can't give you an exact time in years, 
because every time a vaccinologist does that, he or she gets 
burned. So I'll refrain from that, but I can tell you that we 
clearly are considerably closer than when I spoke to you last 
time at a hearing when we were talking about the possibility of 
getting away from that very frustrating situation where each 
year you have to hopefully guess right, and we do most of the 
time, but not all the time.
    But even more importantly, when we're faced with a pandemic 
flu like we were with the 2009 H1N1, when we made a vaccine 
after isolating the virus, but the production issues were such 
that by the time we got enough to distribute, unfortunately, 
the pandemic had already peaked. Fortunately for us, it was a 
relatively mild one, but that's not going to happen all the 
time.
    So what's happened in the last year since we spoke, Mr. 
Chairman, is that there have been a number of experiments that 
have been conducted both at the NIH and by our grantees and 
contractors, which have really identified components of the 
influenza virus that the body generally does not make a very 
good response to readily, and that part of the virus is the one 
that would give you protection against virtually all strains.
    And one of the reasons is is that it's sort of hidden from 
the view of the immune system. The thing that the immune system 
sees really clearly is the part of the virus that changes from 
season to season, and that really changes a lot when you get a 
pandemic. There's a part of the virus that the body can make an 
immune response to that it doesn't usually see very well.
    So what investigators have done, in a very simple way, is 
that to put that particular component of the virus in a form 
that the body would see it much more sharply and clearly. This 
has been done in animal models and proven to be inducing 
responses that are good against decades of changes of 
influenza.
    And, now, those studies are being done in what we call 
phase I trials in humans, and the early work indicates that, 
clearly, it looks quite safe, and, second, it is inducing 
responses that span multiple years.
    So I believe it's really just a matter of time. As you 
know, clinical trials, when you want to prove safety and 
efficacy over a period of time, naturally would take years, but 
it's on a track that I believe it's going to happen. I don't 
think it's going to be a question of if. It's going to be a 
question of when. So we're really quite excited about it.
    And that's a very good example of that transition from 
fundamental basic research observations on molecules and their 
confirmation and how that ultimately gets translated into 
something that, if successful, is going to have enormous public 
health benefit.
    Senator Harkin. Well it would. I mean, the amount of just 
savings alone on annual flu shots would be incredible, aside 
from the fact that you wouldn't--I would, from what I 
understand is if this was really developed, the threat of 
pandemics would not be as large as they are now either.
    Dr. Fauci. The ultimate goal is to have on the shelf, ready 
for utilization a vaccine that does have the universal 
characteristics to it, so that if you do get a change with a 
pandemic, that you can actually have that particular virus be 
covered by it.
    So we'd like to get it to the form--I don't think it's 
going to be perfectly this way, Mr. Chairman, but it's going to 
be close. I don't think it's going to be one flu vaccine and 
that's it for the rest of your life.
    It'll probably be having to be given every several years to 
continue to boost the immune system, but we would like to be 
the way we are, for example, with measles or hepatitis or 
polio, where you just make a lot of it, you have it available 
and when you need it, you deploy it, as opposed to having to 
play catch up every single time a new virus emerges.

                           MEDICAL MILESTONES

    Senator Harkin. Very good.
    Dr. Varmus, in 2001, Gleevec was on the cover of all our 
national news magazines, talked about it being the magic bullet 
that would herald in a new age in the war against cancer. For 
the first time, we had a drug that specifically targeted a 
known cancer gene. It took this deadly blood disease, turned it 
into a chronic, but survivable condition.
    We were told that Gleevec was the promise of the future. We 
talked about it in our subcommittee hearings at that time, but 
that was 10 years ago. We haven't had any other Gleevecs. 
What's happened? How come no more Gleevecs?
    Dr. Varmus. Well, I wouldn't characterize it quite that 
way, Senator. Gleevec remains the poster child for targeted 
therapy.
    Senator Harkin. Yes.
    Dr. Varmus. And just to give you a brief update, it's used 
not only for the treatment of chronic myeloid leukemia, the 
leukemia you heard about, it's used for the treatment of 
several other diseases in which potential targets for the drug 
are mutated, and that includes gastrointestinal stromal tumors, 
a number of other blood diseases, and, indeed, a few other 
diseases in a few cases in which certain genes are known to be 
mutated as a result of analysis of the genome of those cancers.
    Moreover, it's recently been shown that we can deal with 
drug resistance, a common problem in cancer therapy, by using 
drugs closely related to Gleevec but not identical to it and to 
treat patients who become resistant to Gleevec.
    Second, it's been shown recently that a person in their 40s 
or 50s who develop--leukemia now have a normal life expectancy, 
which was previously 5 years. That's a dramatic change and it 
shows that the efficacy of Gleevec has been sustained over the 
last 10 years, and, actually, the evidence that it's effective 
is only strengthened.
    There are a number of other targeted therapies. They tend 
to work quite well initially. Patients become--their tumors 
become resistant to therapy. Let me give you a couple of 
examples.
    One happens to involve my own work on lung cancer, which is 
a significant percentage, perhaps 10 percent, of cancers have 
mutations in some specific genes against which we have 
effective inhibitors, but, generally speaking, within 1 year or 
so, on average, patients become resistant to those drugs. We 
don't have good therapies to counter the tumors that are 
resistant.
    Recently, in the case of a disease called metastatic 
melanoma, a disease that is secondary to finding a skin tumor, 
but the tumor has spread to the liver, bones, and other sites, 
it's been found as recently as 7 or 8 years ago, that about 60 
percent of those cancers have a mutation in a specific gene 
against which an inhibitor has been developed.
    It's extremely effective, again, in inducing remissions in 
a fairly non-toxic way. This is, again, an orally available 
drug that promotes a dramatic regression in the size of tumors.
    There are two drugs that do this. They are very likely soon 
to be approved by the FDA. They don't cause persistent 
regressions, but there's every reason to hope that additional 
drugs will be on the way to help counter drug resistance.
    So I would say that we've had a number of other targeted 
therapies. They have not, in general, been quite as dramatic as 
Gleevec, but most of us who are working in this area are quite 
optimistic about a number of new drugs, some of which I haven't 
mentioned, that are in the pipeline.
    Senator Harkin. That drug you mentioned about metastatic 
melanoma, you mentioned it in your written testimony.
    Dr. Varmus. Correct.
    Senator Harkin. What's the name of the drug? I forget----
    Dr. Varmus. Well, there are two things that I mentioned in 
my testimony, Senator, first was these so-called inhibitors of 
BRAF. These drugs are not yet on the market. One comes from 
Flexicon, one from GlaxoSmithKline (GSK).
    Senator Harkin. Yes.
    Dr. Varmus. There's also a new immunotherapy called 
ipilimumab, which has been approved by the FDA. That's not the 
same kind of targeted therapy, but it's a dramatic development, 
because it's one of the first immunological approaches.
    There are others, but this is one of the first that 
actually displays how we can manipulate our understanding of 
the immune system to galvanize the response of the immune 
system against a variety of cancers, including melanoma.
    Senator Harkin. But I can't even pronounce that word, 
ipilimumab?
    Dr. Varmus. Ipilimumab.
    Senator Harkin. Thank you very much.
    Dr. Varmus. Yes, I'm not responsible for that, Senator. It 
would not have been my choice. Ipi for short.
    Senator Harkin. It seems to me this is about as important 
as Gleevec. I mean, this attacks metastatic melanoma in later 
stages.
    Dr. Varmus. Correct.
    Senator Harkin. And this has always been a death sentence 
before.
    Dr. Varmus. As does the drug that inhibits the BRAF 
mutation. But ipilimumab does not work in all cases, but does 
prolong life significantly in a very substantial 15 to 30 
percent of patients who have metastatic melanoma. It is a major 
development, no question about it.
    One of the open questions is why do a certain subset of 
patients with this disease respond and others not respond.
    There are other inhibitors of the so-called brakes on the 
immune system that are in development, and I think may be 
combined with ipilimumab or used as an alternative when 
ipilimumab doesn't work.
    So we're quite optimistic after many years of trying to 
manipulate the immune system that we have some very serious 
handles on how the immune system works that we can use in 
cancer therapies.
    Senator Harkin. Very good. Thanks, Dr. Varmus.
    Recognize Senator Shelby, then I see Senator Kirk has 
joined us. I'll go to Senator Kirk next.

       ACADEMIA-INDUSTRY COLLABORATION TO REPURPOSE DRUG COMPOUND

    Senator Shelby. Thank you.
    Dr. Collins, repurposing drugs, you alluded to that 
earlier. As we have searched for treatments, as you do, and 
others, investigators, to the healthcare challenges, one of the 
clear ways that some people believe we can continue drug 
development is by finding new uses for drugs that were 
discontinued or halted mid-development. By leveraging existing 
compounds, researchers in industry can develop and have new, 
novel treatments for patients.
    It's my understanding that the NIH recently held a 
roundtable discussion regarding rescuing and repurposing 
compounds. Seems like that's an ideal opportunity for academia 
to team with industry to bring treatments to patients faster. 
Could you expand on that? What are you doing here and how?
    Dr. Collins. I'd be happy to, Senator, because this is a 
really exciting potential area to speed up the process of 
developing new treatments for diseases that currently lack 
effective interventions, and it's another example of the kind 
of thing that NCATS will be able to catalyze just by its 
convening power.
    Yes, we did have this meeting just about 10 days ago. We 
invited major leaders from pharmaceutical and biotech 
industries to meet with NIH investigators, with academic 
experts and to ask the question: Are there in fact, already 
sitting in medicine bottles or in freezers of companies that 
have tried various compounds and abandoned them along the way 
opportunities to take molecules about which we already know a 
lot and find a new use for them?
    Senator Shelby. Do you have any examples or is it too 
early?
    Dr. Collins. We have some very striking examples. Maybe 
I'll even ask Dr. Shurin to tell the example of Marfan 
syndrome. So let me set this up.
    Marfan syndrome is a genetic condition caused by a single 
glitch in a gene called fibrillin and is characterized by very 
tall stature, and, unfortunately, by a high risk of an aortic 
dissection, which is often fatal. So Flo Hyman, the volleyball 
star, died suddenly because of that condition, and it's not 
that rare.
    And many of us thought, well, we'll never come up with a 
therapy for that in the next 50 years, because it's too rare 
for there to be much economic interest, but something pretty 
interesting happened. Do you want to tell that story?
    Dr. Shurin. One of our investigators at Johns Hopkins, Dr. 
Hal Dietz, discovered that a drug, losartan, which is used for 
blood pressure--it's an approved drug--actually cures Marfan 
syndrome, not only in the test tube, but also in mice.
    And so we were able, using our existing Pediatric Heart 
Network, to rapidly launch a clinical trial. We had the first 
patient enrolled about 5 months after we had opened the trial 
and, working very closely with the Marfan Foundation, have been 
able to complete enrollment.
    The results are not yet fully available. The trends are 
looking very good, and we've been very excited by this. But the 
ability to do this with the cooperation of the drug 
manufacturer and the patient advocacy groups has been really 
quite spectacular.
    Dr. Collins. So that's an example.
    My own lab works on a disease called Progeria, the most 
dramatic form of premature aging. These kids age about seven 
times the normal rate and usually die by age 12 or 13 of heart 
attack or stroke.
    By discovering the genetic cause of that disease, 
understanding the pathway that's involved, it became clear that 
a drug class developed for cancer might actually turn out to be 
beneficial in this premature-aging disease.
    They've just completed a 2-year clinical trial on kids with 
Progeria using this supposed cancer drug, and while the results 
are not yet published, I'm hearing very encouraging noises. So 
it's repurposing a very different idea of what that drug would 
be used for for a new application.
    I am sure that if we had a systematic way of trolling the 
landscape to identify other such opportunities there would be 
lots more.

                      INTER-AGENCY COLLABORATIONS

    Senator Shelby. Dr. Collins, dealing with NIH-FDA 
collaboration, which is, I think, is very important, what do 
you think would be the best results to come from increased NIH-
FDA collaboration? Are there topics in particular that you're 
working on with the NIH and partnering there to move--I assume 
moving drugs to market and getting them approved safely is very 
important.
    Dr. Collins. Commissioner Margaret Hamburg and I have been 
meeting for now almost 2 years to talk about ways that our 
agencies could work more closely together. And she is a strong 
advocate, and I share that same view with her, that regulatory 
science--that is, applying science to how reviews are done of 
drugs and devices--is very much a possible solution to the 
current logjam of trying to get products through that pipeline.
    Senator Shelby. We would all benefit from that, wouldn't 
we?
    Dr. Collins. We would, indeed.
    And so she and I have together started a regulatory science 
research program. We formed a leadership council between the 
two of us which involves the senior leadership of both of our 
agencies. We've identified six areas that we think are 
particularly ripe for progress, such things as how do you do 
toxicology more efficiently? How do you deal with combination 
therapies like Dr. Varmus was mentioning may be necessary for 
cancer when, in fact, that's hard to review. You have to come 
up with new ways to look at that.
    And I think together, working as sister agencies, we can 
make progress that neither of us could have done alone, and 
we're totally committed to making that happen.
    Senator Shelby. How do you collaborate with CDC?
    Dr. Collins. Oh, quite intensively.
    Senator Shelby. I know you do.
    Dr. Collins. Tom Frieden, the head of CDC, and I were on 
the phone yesterday, and that happens regularly, about areas of 
shared interest, and that includes global health as well as 
domestic issues.
    He and I have exchanged people by going back and forth to 
look at shared projects. We obviously work very closely in the 
area of infectious disease.
    Maybe Dr. Fauci would want to make a comment about your 
relationship with CDC, because it's so important.
    Dr. Fauci. Yes. We have very strong and long-standing 
collaborations, particularly in the arena of global health with 
the emphasis on infectious diseases, even though global health 
certainly encompasses more than just infectious diseases.
    An example of that is we share some of our sites. The CDC 
has epidemiological sites and posts for surveillance of 
disease. We are now incorporating many of those sites in our 
clinical trials of drugs, so many of the trials that take place 
are really strong collaborations between the CDC and the NIH, 
and that's worked very well.

                            CYSTIC FIBROSIS

    Senator Shelby. Dr. Collins, I enjoyed seeing you last 
night, and you know better than anybody that they've come out 
with a new drug in the treatment of lupus for many things. 
That's a breakthrough of many, many years.
    What about cystic fibrosis? Where are you in this area? I 
know you've done a lot of research in that area, too.
    Dr. Collins. Senator, I appreciate the question. I enjoyed 
the experience of chatting with you last night at the Lupus 
Foundation of America event. And they are very excited, and 
justifiably so, at the approval of Benlysta, this first drug 
for lupus in a long time.
    Cystic fibrosis is an area of intense interest for me, 
because I was part of the team that found the cause of that in 
1989, and that has now, finally, after many years of struggle, 
led to a very exciting time therapeutically.
    So just in the last few months, a drug developed using this 
same approach to try to identify small molecules, the same kind 
of thing that Senator Moran was seeing in Kansas, this, in this 
case, done as a partnership with a company called Vertex, found 
a molecule which goes by a not terribly friendly name, VX-770, 
which, in fact, for that category of patients with cystic 
fibrosis who have a particular mutation in the gene, appears to 
be highly effective, and taken over the course of just a month 
improves lung function. It reduces the sweat chloride, which 
has been the diagnostic hallmark of cystic fibrosis----
    Senator Shelby. This has been out how long now?
    Dr. Collins. This is still in clinical trials. It hasn't 
yet been approved by the FDA, but the phase III trial results 
look extremely promising.
    Senator Shelby. That would herald, if it were approved by 
FDA--It's in clinical trials now.
    Dr. Collins. That would be an enormous step forward.
    Senator Shelby. A huge breakthrough, hopefully, for cystic 
fibrosis.
    Dr. Collins. Now, the down side is that this particular 
drug is only likely to be effective in that subset of patients 
with cystic fibrosis who have a particular mutation in the 
cystic fibrosis gene. The common mutation would not necessarily 
respond to this drug. You wouldn't expect it would.
    There is another drug in the pipeline a few steps behind, 
VX-809, which is targeted toward the common mutation. We all 
have high hopes that that will turn out to be just as 
effective, but we have to wait and see what the clinical trials 
show.
    Senator Shelby. But it holds promise for the people with 
cystic fibrosis and their families.
    Dr. Collins. I've been in this field for 25 years. I've not 
seen more excitement and hope about a therapeutic intervention 
in that whole time until now.
    Senator Shelby. Thank you.
    Senator Harkin. Thank you.
    Senator Kirk.

                   HEALTHCARE SPENDING POLICY OPTIONS

    Senator Kirk. Thank you, Mr. Chairman, and I'm sort of 
overawed to see this group here. I followed in the Congress 
Congressman John Porter, very much a supporter of NIH and 
Research!America.
    And, to me, it's interesting, in these times of deficits 
and debt in which the largest bond purchaser in America, Pimco, 
has now divested itself of all U.S. Treasury securities, 
because he's worried about the long-term future of us being 
able to borrow money.
    I just met with one of the Chinese top officials in meeting 
Secretary Clinton, and they also talked about how they were 
making moves to leave U.S. debt.
    And so it's--over the long term, I wonder how we might be 
able to borrow the kind of monies that are being thought of.
    With these kind of limitations, you wonder, then, what 
direction you take with regard to healthcare policy. And there 
are obviously two main directions, if the Government is to 
support it, and that is to subsidize care or to subsidize 
research.
    Now, in subsidizing care, I guess the rough numbers are 
Medicare is now $370 billion and Medicaid is $300 billion. So 
that's very, very expensive now and growing quite rapidly, but 
$670 billion in the subsidizing care path.
    In the subsidizing research, NIH comes in at $26 billion, 
and yet I think offers a much brighter future of a virtuous 
cycle of better and better patient outcomes, faster and faster 
innovation and dramatic reversals in disease outcomes, as we've 
seen in several cancers or, for example, in juvenile diabetes.
    And so in a resource-constrained area--and I think either 
the Congress is going to make budget cuts or the bond market is 
going to make budget cuts to the Federal budget--you then say 
do we double down on subsidizing care or do we continue on the 
funding research side, and because this also has a huge 
economic benefit to the United States, I very much favor NIH, 
where I worry about the long-term sustainability of other parts 
of the budget.
     So let me ask you somewhat of a theological question on 
how we move forward in this environment, which is the 
President's healthcare bill set up an independent payment 
advisory board to ration care and basically to deny care in 
several areas. Its goal, I think, over time will be to 
replicate the power and authority of the British NIH's NICE 
rationing board.
    Have we thought about NIH's relationship to IPAB and how we 
would advise the people who would be denying care under 
Medicare how they would keep up with medical research and 
technology?
    Dr. Collins. So these are difficult questions indeed, 
Senator. NIH's role as the prime supporter of biomedical 
research is to provide the evidence that is necessary for 
making wise healthcare decisions, but, obviously, those 
decisions depend on more than just the scientific evidence. 
They also depend on how society wants to expend its resources.
    But I think we can help in substantial ways with the very 
frightening cost curve that otherwise faces us. If you'll 
permit me, I'd just like to show you one example of the kind of 
looming problem that we have in front of us if nothing is done.




    This curve shows you for one disease, Alzheimer's disease, 
what we are currently spending, which in 2010 is about $180 
billion, and which by the projections that many people have 
made, if nothing is done, if research is unsuccessful or not 
supported, will rise to more than $1 trillion just for that one 
disease in 2050, and the number of effected individuals at that 
point will be in the neighborhood of 13 million. One disease.
    And, yet, at the present time, our investments in research 
on Alzheimer's disease fall somewhat less than $1 billion. So, 
clearly, we feel a great responsibility to move that curve in a 
different direction. If we could even come up with a 
therapeutic approach that would slow the onset of disease, 
delay it by 5 years, you could cut these costs almost in half, 
and, obviously, something more dramatic would have an even more 
beneficial effect. That's what we see as our mission----
    Senator Kirk. I'm just wondering--My time has run out, but 
if we--I think IPAB's future depends on the presidential 
election. Should the President prevail, then IPAB and the 
healthcare bill is with us. Should the President be defeated, I 
think that much of the healthcare bill will be wiped out and 
IPAB with it.
    But on the potential that the President is reelected, have 
you thought about--because what I'm worried about is IPAB will 
become an incredibly bureaucratic, stultified organization. It 
will review diseases and protocols, but the danger is that they 
will be working on heart disease and a breakthrough comes in 
cancer that revolutionizes research and they will not have the 
bureaucratic means to switch and then advise for a new payment. 
And we have such a pace of innovation that a huge state 
bureaucracy inevitably will slow down and be unable to keep 
pace with medical innovation.
    In fact, I would actually argue it probably will kill a lot 
of medical innovation as it locks in payment methodologies the 
way Medicare has.
    But have you begun to think about how you might relate to 
this new bureaucracy?
    Dr. Collins. Well, again, Senator, I think our best answer 
to that is to do the rigorous research that actually not only 
tries new therapeutic approaches, but also does comparisons, 
when there's more than one alternative, to see what works, and 
then to do what we do routinely, and which we believe is a 
strong part of our job, is to make that data immediately 
available, publish it, make sure it's propagated so that nobody 
is left in the dark about knowing what the results have been.
    And then I guess I'm just enough of an optimist to think if 
the data is there and if it's compelling, it'll be hard to 
ignore. But I hear your concern.
    Senator Kirk. I would just simply finish up by saying 
should IPAB not survive--I hope it doesn't, but should it 
survive I think we might want to think about a more formal data 
transmission between NIH and IPAB, because, otherwise, IPAB, I 
think, will rapidly cause Medicare to fall behind technology 
and innovation.
    Thank you, Mr. Chairman.
    Senator Harkin. Senator Moran.

                 EFFECTS OF RESEACH ON HEALTHCARE COSTS

    Senator Moran. Mr. Chairman, thank you again.
    Dr. Collins, perhaps my question is in ways related to the 
Alzheimer's chart you just showed, which was a request that do 
you have information to substantiate my suggestion or a belief 
that money spent on biomedical research results in cost savings 
in healthcare? Is there that kind of science-based fact that 
substantiates my feelings?
    Dr. Collins. So those are complex economic analyses, and 
even economists will tend to disagree with each other about the 
right way to do it. Let me just cite a couple of figures, 
though.
    If you look, for instance, at heart disease, what's 
happened in the last 40 years, Dr. Shurin will tell you we've 
seen a 60-percent drop in mortality from heart attack during 
those 40 years. The cost of that, if you average it out per 
American per year, in terms of the research that led to those 
advances, beginning with the Framingham Study, going through 
with the development of understanding about cholesterol and 
ultimately the development of statins, was about $3.70 per 
American per year, the cost of a latte, and not even a grande 
latte, that would be a tall, I think.
    So and if you add up the economic benefits that have 
resulted from the increase in longevity that have occurred 
between 1970 and 2000, I am told credible economists believe 
that adds up to $91 trillion. Michael Milken, in a recent 
editorial in The Wall Street Journal runs through a lot of 
those figures and they seem to be cited by reasonable experts.
    If we were to diminish the frequency of cancer by just one 
percent--and that's actually happening each year. Each time the 
frequency of cancer goes down by 1 percent, economists say 
that's saving our country $500 billion in terms of economy that 
is sustained as a result of having those people with us. So the 
return is enormous.
    I could cite you specific examples of new technologies, but 
the big picture is quite compelling.

                      RARE AND NEGLECTED DISEASES

    Senator Moran. Well, I'm not surprised by that. It would be 
very helpful to have that--I don't like the word sound byte, 
but that phrase that says for every dollar spent, here's what 
we're able to save in otherwise spending on healthcare.
    Let me go back to something more specific and just ask you 
to elaborate upon the value of academic and nonprofit research 
institutions' role in developing therapies and treatments for 
rare and neglected diseases through NCATS, as you propose, and 
through your therapeutic and rare neglected disease program 
that you already have.
    I mean, is this something that you envision as having a 
significant role in the future as you develop NCATS are these 
neglected diseases?
    Dr. Collins. Indeed. And, in fact, the 27 Institutes and 
Centers at NIH have been engaged in such efforts for rare and 
neglected diseases for some time.
    We expect that the advent of NCATS serving as a hub of this 
activity will further encourage that and hopefully contribute 
innovations that will result in more rapid progress and also a 
lower failure rate.
    The TRND Program, Therapeutics for Rare and Neglected 
Diseases, which the Congress authorized 2 years ago, is 
specifically devoted to identifying projects that might 
otherwise sit there untouched, where there's a real promise in 
taking a therapeutic and moving it into the preclinical space, 
which is often called the Valley of Death, because that's where 
often good projects go to die.
    Take example sickle-cell disease. There's a TRND Program 
right now pursuing an interesting therapeutic for sickle-cell 
disease originally identified at a university, Virginia 
Commonwealth University, then licensed out to a biotech 
company, AESRX.
    The biotech company carried it to a certain level and then 
ran out of money, and venture capital is hard to find these 
days unless you have something that's going to result in 
profits within a couple of years.
    So the company has now partnered with the NIH to move this 
forward. The preclinical studies look very good. This will, as 
I understand it, be submitted to the FDA for an IND application 
later this year, and clinical trials may well get under way 
within 1 year at our NIH Clinical Center.
    If this were successful, this would be a radical new 
approach to sickle-cell disease. The way this molecule works is 
unlike anything that's been tried for this disease before.
    And while this is certainly a neglected and relatively rare 
disease, it still affects tens of thousands, hundreds of 
thousands of individuals in this United States and many more 
across the world. So it's a good example of a way in which NIH 
may be able to assist in the current scientific environment to 
move projects forward that otherwise would have languished.
    Senator Moran. Thank you very much. Mr. Chairman, thank 
you. And let me express my gratitude to all of you for your 
public service.
    Senator Harkin. Well, I want to thank you all for being 
here, again, for another enlightening session.

                     ADDITIONAL COMMITTEE QUESTIONS

    I have some other questions I won't propound now, but I'll 
submit those in writing, and the record will remain open for a 
week for other Senators to submit further questions or 
statements.
    [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

  NATIONAL CENTER FOR COMPLEMENTARY AND ALTERNATIVE MEDICINE (NCCAM) 
                            ADVISORY COUNCIL

    Question. The statute for the NCCAM stipulates that of the 18 
appointed members of the Center's Advisory Council, 9 must be 
practitioners licensed in one or more of the major systems with which 
the Center is concerned, and at least three shall represent the 
interests of individual consumers of complementary and alternative 
medicine. Is the NCCAM meeting this requirement? Of the four new 
members announced on June 6, 2011, how many meet one of the two 
categories described above?
    Answer. The composition of the National Advisory Council for 
Complementary and Alternative Medicine meets the statutory requirements 
concerning membership. Collectively, its membership includes the 
expertise required for it to carry out its requirements to provide 
second level peer review and other advice across the broad and varied 
spectrum of clinical practice and scientific disciplines which fall 
under the Center's mandate.
    On Friday, June 3, 2011, four new members joined the NCCAM Advisory 
Council. Brian M. Berman, MD, LAC, is a licensed physician and 
acupuncturist. James Lloyd Michener, MD, is professor and chairman of 
the Department of Community and Family Medicine and Director of the 
Duke Center for Community Research. Dr. Michener also represents the 
interests of individual consumers of complementary and alternative 
medicine (CAM). Daniel C. Cherkin, Ph.D., is an epidemiologist and 
highly experienced clinical researcher who has conducted a number of 
major studies that have provided evidence for benefit of CAM therapies 
(including chiropractic manipulation, acupuncture, and massage) for low 
back pain. David G.I. Kingston, Ph.D., is a widely respected natural 
products chemist whose research focuses on the chemistry of 
biologically active natural products and the discovery of new therapies 
for cancer and malaria from plants.

                      THE NCCAM RESEARCH SUCCESSES

    Question. Under the statute that created the NCCAM, the general 
purposes of the Center include ``identifying, investigating, and 
validating complementary and alternative treatment, diagnostic and 
prevention modalities, disciplines and systems.'' Please identify all 
instances in the past 10 years in which the NCCAM-supported research 
has validated complementary and alternative treatment, diagnostic and 
prevention modalities, disciplines and systems.
    Answer. The NCCAM is strongly committed to the highest standards of 
evidence-based medicine. Validating health interventions is a process 
that begins with evidence developed in peer-reviewed basic and clinical 
research. Next, the evidence from multiple studies is collectively 
assessed through formal systematic review methods. Finally, if these 
earlier steps indicate sufficient usefulness and safety, professional 
organizations and health policy makers undertake the development of 
guidelines and recommendations regarding use and clinical practice. 
This process, collectively referred to as evidence-based medicine, 
entails assimilation of the body of scientific evidence; almost never 
does a single study result in consensus that an intervention is valid.
    Eleven years ago, when the NCCAM was created, there was no 
significant evidence-base on the biological properties, safety, and 
efficacy of the vast majority of CAM modalities. The Center's first 
decade was therefore focused on the conduct and support of basic and 
applied research that addressed this lack of scientific information. 
The results of that investment now include an emerging evidence base 
that is dramatically stronger in terms of both quality and quantity. 
Basic research and clinical trials, large and small, have yielded 
results--both ``positive'' and ``negative''--regarding the effects, 
efficacy, safety, and in some cases, promise regarding CAM 
interventions.
    Critically, sufficient evidence regarding some CAM interventions 
has now been developed to permit informative evidence-based analyses 
and systematic reviews by independent organizations (e.g., the Cochrane 
Collaboration) using the rigorous standards of evidence-based medicine. 
Indeed, such analyses now point increasingly toward clinically helpful 
conclusions regarding usefulness and safety--or lack thereof--of 
specific CAM interventions and practices.
    Notably, the expanding evidence base now includes a large body of 
science that points toward specific, very promising opportunities to 
improve healthcare and health promotion using CAM-inclusive strategies. 
These opportunities are reflected directly in the NCCAM's recently-
released third strategic plan. Important examples include the 
following:
Mind and Body Practices
  --Developing better, comprehensive strategies for management of 
        chronic back pain and defining the roles of acupuncture, spinal 
        manipulation, and massage in those strategies
  --Exploring the role of specific promising CAM practices or 
        disciplines (e.g., meditation, yoga, or acupuncture) in 
        developing better strategies for alleviating symptoms (e.g., 
        chronic pain, stress) or in promoting healthier lifestyles
  --Exploring the associations between well-characterized pathways of 
        pain processing and acupuncture analgesia or the placebo 
        response
  --Exploring the associations of major pathways of cognitive 
        processing and emotion regulation by meditative practices
  --Studying the influence of the provider-patient/client interaction, 
        context effects, and the placebo response on outcomes of CAM 
        interventions
Natural Products
  --Studying the molecular targets and biological effects of 
        potentially beneficial small molecules that are constituents of 
        natural products or diet (e.g., quercetin, curcumin, or other 
        polyphenols and flavonoids)
  --Defining the anti-inflammatory actions of omega-3 fatty acids
  --Employing state-of-the-art tools and technologies to study the 
        effects of probiotics on the human microbiome
  --Developing evidence regarding the safety profile of certain widely 
        used natural products, including interactions with drugs and 
        other herbals or dietary supplements
    The growing evidence base is clearly influencing professional 
practice guidelines of mainstream professional medical societies, and 
the practice of integrative medicine. Complementary and alternative 
therapies are increasingly being accepted and integrated into 
conventional healthcare systems. For example, recent data show that 
approximately half the hospices in the United States and 9 out of 10 
Department of Veterans Affairs facilities offer some complementary or 
alternative therapies. The Consortium of Academic Health Centers in 
Integrative Medicine, an organization of integrative medicine 
departments at academic medical centers, has grown from 11 members in 
2002 to 43 members in 2011. Medical societies such as the American 
College of Physicians, the American Academy of Pediatrics and the 
American Academy of Family Physicians have formulated policies 
regarding complementary therapies and offer educational material about 
these forms of treatment. The Departments of Defense and Veterans 
Affairs are also actively pursuing care and research initiatives that 
include various CAM interventions in treatment and prevention of 
problems such as chronic pain and post-traumatic stress disorder 
afflicting our wounded warriors.
    In the appendices, we have included a status report on the process 
of validation of selected interventions. In Appendix A, we present 
examples of specific complementary and alternative interventions for 
which a sufficient number of individual studies exist for systematic 
reviews to conclude the interventions appear to offer benefit. In 
Appendix B, we list numerous additional examples of individual NCCAM-
supported studies that provide preliminary evidence of benefit in other 
indications. We feel it important to provide both types of information 
in addressing the subcommittee's specific questions because the 
processes of evidence-based validation of health practices and 
decisionmaking regarding their use are iterative, and draw on a variety 
of such sources rather than merely single studies.

 APPENDIX A: THE STATUS OF THE EVIDENCE BASED REVIEWS AND PROFESSIONAL 
     GUIDELINES FOR SELECT COMPLEMENTARY AND ALTERNATIVE THERAPIES

    The examples of systematic reviews and professional assessments 
cited here all include evidence derived from clinical and mechanistic 
research supported by the NCCAM. As is true with the evidence in most 
areas of healthcare, there continues to be controversy about some of 
these conclusions, and not all systematic reviews come to the same 
conclusions.

Role of Complementary Therapies in the Management of Chronic Low Back 
        Pain
    Management of chronic low back pain is a critical challenge for our 
healthcare system and a major driver of healthcare costs. Complementary 
interventions are increasingly being integrated into the care of 
chronic back pain patients, and there is substantial recognition, 
supported by findings from the NCCAM research, that complementary 
therapies, particularly chiropractic and osteopathic spinal 
manipulation, massage, acupuncture, and meditative exercise forms such 
as yoga, can make important contributions to improved outcomes for 
patients. Many systematic reviews have assessed these therapeutic 
approaches. The Joint Clinical Practice Guideline for low back pain, 
developed by the American College of Physicians and the American Pain 
Society, reflects the strength of this evidence base and the emerging 
professional consensus for the value of the incorporation of 
complementary approaches. To quote directly from the summary:

    ``For patients who do not improve with self-care options, 
clinicians should consider the addition of nonpharmacologic therapy 
with proven benefits-for acute low back pain, spinal manipulation; for 
chronic or sub-acute low back pain, intensive interdisciplinary 
rehabilitation, exercise therapy, acupuncture, massage therapy, spinal 
manipulation, yoga, cognitive-behavioral therapy, or progressive 
relaxation.''--Joint Clinical Practice Guideline, American College of 
Physicians and American Pain Society. Annals of Internal Medicine, 
2007: 147,478.

    Nevertheless, there is also a consensus among healthcare providers, 
both conventional and complementary, that, current approaches are not 
satisfactory for many patients suffering with back pain. Moving 
forward, a major area of emphasis for the NCCAM, as described in the 
NCCAM's 2011 Strategic Plan, will be improving management of chronic 
back pain. Research is needed to optimize complementary therapies, to 
understand better who benefits from them, and to develop better systems 
of integrated care that improve real world application of these helpful 
therapeutic techniques.
Role of Natural Products in Promotion of Health and Wellness
    The NCCAM's natural product research portfolio, carefully assessed 
during our strategic planning process, has yielded many important 
lessons that will guide us moving forward. Fundamental scientific 
understanding of potential beneficial mechanisms of many dietary 
supplements and natural products has increased markedly, with some 
notable examples described below. New high-throughput technologies and 
modern genomic tools have created important new scientific 
opportunities. We have learned much about the challenges of translation 
of these findings to clinical efficacy research. The future emphasis, 
as described in our strategic plan and strongly supported by both 
academic investigators and leaders of the botanical and dietary 
supplement industry, is on the development of strong biological 
mechanistic hypotheses, sensitive biological signatures of effect, and 
carefully optimized trial designs.
    A few examples of the independent systematic reviews that have 
provided validation of the potential value of natural products or other 
dietary supplements are as follows:
  --Fish Oil for the Prevention of Cardiovascular Disease.--``Dietary 
        supplementation with omega-3 fatty acids should be considered 
        in the secondary prevention of cardiovascular events.''--
        Clinical Cardiol. 2009: 32, 365.
  --Melatonin for the Prevention and Treatment of Jet Lag.--``Melatonin 
        is remarkably effective in preventing or reducing jet lag, and 
        occasional short-term use appears to be safe.''--Cochrane 
        Database Syst Rev 2002: 1520.
  --Probiotics for Prevention of Necrotizing Enterocolitis in Preterm 
        Infants.--``Enteral supplementation of probiotics prevents 
        severe necrotizing enterocolitis and all cause mortality in 
        preterm infants.''--Cochrane Database Syst Rev 2008: 5496.
  --Prebiotics and Probiotics for Hepatic Encephalopathy.--``The use of 
        prebiotics, probiotics and synbiotics was associated with 
        significant improvement in minimal hepatic encephalopathy.''--
        Ailment Pharmacol Ther 2011: 33.
  --Probiotics for Acute Infectious Diarrhea.--``Used alongside 
        rehydration therapy, probiotics appear to be safe and have 
        clear beneficial effects in shortening the duration and 
        reducing stool frequency in acute infectious diarrhea.''--
        Cochrane Database Syst Rev 2010: 3048.
  --Zinc for the Common Cold.--``Zinc administered within 24 hours of 
        onset of symptoms reduces the duration and severity of the 
        common cold in healthy people.''--Cochrane Database Syst Rev 
        2006: 1364.

Role of Complementary Therapies in the Management of Pain and Other 
        Troublesome Symptoms
    Concern is often voiced that the processes of evidence-based 
medicine could not accommodate the evidence emerging from research on 
many complementary therapies. In fact, this is a challenge common to 
evaluation of the evidence of many nonpharmacological interventions, 
including psychotherapy and surgery. The NCCAM's strategic plan 
addresses this challenge by calling for increased use of outcomes and 
effectiveness research methodology, and collaboration with experts who 
work in other fields facing similar challenges. Nonetheless, several 
examples are provided below which illustrate that rigorous research on 
these complicated therapies is possible and can meet the exacting 
standards of evidence-based review.
  --The Cochrane Collaborative has reviewed the evidence that 
        acupuncture may provide benefit for migraine prophylaxis and 
        for treatment of tension-type headache, and concluded that it 
        has value in both situations.--Cochrane Database Syst Rev 2009: 
        1218, Cochrane Database Syst Rev 2009: 7587.
  --The Cochrane Collaborative has reviewed the evidence that 
        acupuncture may be useful for postoperative nausea and 
        vomiting, as well as for nausea and vomiting which has been 
        induced by cancer chemotherapy. Systematic reviews conclude 
        benefit in both cases.--Cochrane Database Syst Rev 2009, 3281, 
        National Cancer Institute, PDQ summary.
  --A systematic review published in the British Journal of Anesthesia 
        concluded that perioperative acupuncture is a useful adjunct 
        for acute postoperative pain management.--Br. J Anaesth 2008: 
        101, 151.

APPENDIX B: THE NCCAM-SUPPORTED STUDIES THAT CONTAIN EVIDENCE OF VALUE 
                                 OF CAM

    Listed below are the NCCAM-supported studies, which contain 
evidence of the value of CAM. Consistent with the priorities of the 
NCCAM's strategic plan, these findings are grouped into three major 
categories: Mind and Body Interventions; Natural Products 
Interventions; and Population-Based Research. Within each category, the 
findings are listed in reverse chronological order by the publication 
date.

Mind and Body Interventions
            Chronic Pain
    Review of CAM Practices for Back and Neck Pain Shows Modest 
Benefit.--According to a recent review published by the Agency for 
Healthcare Research and Quality, the benefits of complementary and 
alternative therapies for back and neck pain--such as acupuncture, 
massage, and spinal manipulation--are modest in size but provide more 
benefit than usual medical care. While these effects are most evident 
following the end of treatment, the authors of the report noted that 
very few studies looked at long-term outcomes. Back and neck pain are 
important health problems that affect millions of Americans, and back 
pain is the most common medical condition for which people use 
complementary and alternative medicine (CAM). They noted that more 
well-designed studies are needed to draw more definitive conclusions 
regarding the benefits of CAM therapies for pain. http://nccam.nih.gov/
research/results/spotlight/100110.htm.--AHRQ Publication No. 
10(11)E007. Rockville, MD: Agency for Healthcare Research and Quality. 
October 2010.
    Tai Chi May Benefit Patients With Fibromyalgia.--Fibromyalgia is a 
disorder characterized by muscle pain, fatigue, and other symptoms. 
Researchers, funded in part by the NCCAM, evaluated the physical and 
psychological benefits of tai chi (which combines meditation, slow 
movements, deep breathing, and relaxation) in 66 people with 
fibromyalgia. The participants were assigned to one of two groups: an 
attention control group that received wellness education and practiced 
stretching exercises, or a tai chi group that received instruction in 
tai chi principles and techniques and practiced 10 forms of Yang-style 
tai chi. Compared with the attention control group, the tai chi group 
had a significantly greater decrease in total score on the Fibromyalgia 
Impact Questionnaire at 12 weeks. In addition, the tai chi group 
demonstrated greater improvement in sleep quality, mood, and quality of 
life. Improvements were still present at 24 weeks. No adverse events 
were reported. The researchers concluded that these findings support 
previous research indicating benefits of tai chi for musculoskeletal 
pain, depression, and quality of life. The underlying mechanisms are 
unknown, and the researchers noted that larger, longer term studies are 
needed to evaluate the potential benefits of tai chi for patients with 
fibromyalgia. http://nccam.nih.gov/research/results/spotlight/
081810.htm.--New England Journal of Medicine. 2010;363(8):743-754 and 
783-784.
    Analysis of National Survey Reveals Perceived Benefit of CAM for 
Back Pain.--According to an analysis of the 2002 National Health 
Interview Survey, approximately 6 percent of U.S. adults used 
complementary and alternative medicine (CAM) to treat their back pain 
during the previous year. The data from this analysis also revealed 
that a majority (60 percent) of survey respondents who used the most 
common CAM therapies for back pain perceived ``a great deal'' of 
benefit. The most common CAM therapies used for back pain--in 
descending order of perceived benefit--were chiropractic (66 percent), 
massage (56 percent), yoga/tai chi/qi gong (56 percent), acupuncture 
(42 percent), herbal therapies (32 percent), and relaxation techniques 
(28 percent). The specific factors associated with a greater perception 
of benefit from CAM use were having an improved self-reported health 
status, and using CAM because ``conventional medical treatment would 
not help.'' Back pain is the most common medical condition for which 
people use CAM, and these data give more insight into the use and 
perceived benefit of CAM therapies for this condition. The researchers 
suggested that this analysis demonstrates the need for future studies 
that include both self-reported outcomes and observer-based performance 
measures of patients using CAM therapies for back pain. http://
nccam.nih.gov/research/results/spotlight/060110.htm.--Journal of the 
American Board of Family Medicine. 2010;23(3):354-362.
    Study of Spinal Manipulative Therapy for Neck-related Headaches 
Reports Findings on Dose and Efficacy.--Previous research suggests that 
spinal manipulative therapy (SMT) may be helpful for various types of 
chronic headaches, including cervicogenic headache (CGH), which is 
associated with neck pain and dysfunction. This randomized controlled 
trial evaluated the dose (number of treatments) and relative efficacy 
of SMT in a group of 80 patients with chronic CGH. Compared with 
massage, participants receiving SMT had greater improvements in CGH-
related pain and disability, lasting to 24 weeks. These differences 
were clinically important and statistically significant. The dose 
effects of SMT treatments (i.e., differences between 8 and 16 
treatments) were small but significant. The mean number of headaches 
reported by SMT subjects decreased by more than half during the study. 
The researchers concluded that their findings support SMT as a viable 
option for treating CGH, but also point out that these findings should 
be considered preliminary. They suggest additional research to 
determine whether SMT results for patients with CGH are affected by 
treatment intensity and duration, use of other therapies, lifestyle 
changes, and an integrative care approach. http://nccam.nih.gov/
research/results/spotlight/041310.htm.--Spine Journal. 2010;10(2):117-
128.
    Preliminary Trial Finds Possible Benefits of Osteopathic Treatment 
for Back Pain During the Third Trimester of Pregnancy.--Most pregnant 
women experience low-back pain, which often is associated with sleep 
disturbance and can affect daily activities. Researchers investigated 
the effects of osteopathic manipulative treatment on back pain during 
the third trimester of pregnancy. They found that back-specific 
functioning deteriorated significantly less in the osteopathic 
manipulative treatment group than in the usual care or usual care with 
sham treatment groups. Although the results of this preliminary study 
suggest that osteopathic manipulation may have benefits for back-
specific functioning, but not pain, in the third trimester of 
pregnancy, larger trials are needed before definitive conclusions can 
be drawn about its efficacy or effectiveness for this purpose. http://
nccam.nih.gov/research/results/spotlight/032210.htm.--American Journal 
of Obstetrics and Gynecology. 2010;202(1):43.e1-43.e8.
    Tai Chi May Benefit Older Adults With Knee Osteoarthritis.--Knee 
osteoarthritis (OA) is an increasing problem among older adults, 
causing pain, functional limitations, and reduced quality of life. 
Researchers conducted a long-term, randomized, controlled trial 
comparing tai chi and conventional exercise in a group of 40 adults 
(mean age 65) with symptomatic knee OA. The tai chi group learned and 
practiced Yang-style tai chi, modified slightly to eliminate excess 
stress on the knees. The control group received wellness education and 
did stretching exercises. Compared with the control group, tai chi 
patients had greater improvement in measures of pain, physical 
function, self-efficacy (belief in one's own abilities), depression, 
and health-related quality of life. Although most differences between 
the two groups were statistically significant only at 12 weeks, the 
differences for self-efficacy and depression remained statistically 
significant at 24 and 48 weeks. No serious adverse events were 
reported. The researchers recommend additional studies of biologic 
mechanisms and approaches of tai chi, so its benefits can be extended 
to a broader population. http://nccam.nih.gov/research/results/
spotlight/011510.htm.--Arthritis & Rheumatism. 2009;61(11):1545-1553.
    Iyengar Yoga for Chronic Low-back Pain Shows Promising Results.--
Researchers conducted a clinical trial to evaluate the effects of 
Iyengar yoga (a popular style of yoga that uses props to help support 
the body during postures) on chronic low-back pain. They found that 
compared with the control group, the yoga group had significantly 
greater reductions in functional disability, pain, and depression, at 
weeks 12 and 24 and at the 6-month followup. There were no significant 
differences in pain medication usage between the groups; however, there 
appeared to be a trend toward decreased usage in the yoga group. The 
researchers concluded from their results that yoga decreases functional 
disability, pain, and depression in people with chronic low-back pain. 
However, they noted potential limitations of their study (e.g., heavy 
reliance on self-report instruments, and differential demands on yoga 
vs. control groups in terms of attention and group support) and suggest 
design considerations for future research. http://nccam.nih.gov/
research/results/spotlight/112409.htm.--Spine. 2009;34(19):2066-2076.
    Managing Low-Back Pain: an Evidence-Based Approach for Primary Care 
Physicians.--A physician's response to a patient with low-back pain 
(LBP) should take into account psychological and social factors as well 
as physical symptoms, according to an article that looked at two case 
studies in light of evidence-based clinical guidelines developed by 
Roger Chou et al. for the American Pain Society and the American 
College of Physicians. The article's authors, recommend a measured 
approach to the use of imaging (x-rays and MRI/CT scans) and 
medication. The authors outline considerations in evaluating each 
patient and choosing action steps. The authors also noted that most 
people with chronic LBP will not become pain free. Physicians can help 
patients have a realistic outlook that focuses on improving functioning 
in addition to reducing pain. http://nccam.nih.gov/research/results/
spotlight/040209.htm.--Journal of Family Practice. 2009;58(4):180-186.
    Study Finds Benefits of Therapeutic Massage for Chronic Neck 
Pain.--In a research study, 64 adults with neck pain persisting for at 
least 12 weeks were randomly assigned to receive either massage or a 
self-care book. The massage group had up to 10 treatments over a 10-
week period, provided by licensed practitioners who used a variety of 
common Swedish and clinical massage techniques and also made typical 
self-care suggestions. After 10 weeks, the massage group was more 
likely than the self-care-book group to have clinically significant 
improvement in function and symptoms. At 26 weeks, the massage group 
tended to be more likely to report improvement in function but not in 
specific symptoms. For both function and symptoms, mean differences 
between the two groups were strongest at 4 weeks and not evident by 26 
weeks. At all followup points, the massage group was more likely than 
the self-care-book group to report global improvement ratings of 
``better'' or ``much better.'' At 26 weeks, medication use had 
increased 14 percent for the self-care-book group but had not changed 
for the massage group. The researchers concluded that therapeutic 
massage is safe and may have benefits for treating chronic neck pain, 
at least in the short term. They recommended studies to determine 
optimal massage treatment, as well as larger, more comprehensive 
studies to follow patients for at least 1 year. http://nccam.nih.gov/
research/results/spotlight/051809.htm.--Clinical Journal of Pain. 
2009;25(3):233-238.
    Massage Therapy May Ease Pain and Improve Mood in Advanced Cancer 
Patients.--Researchers investigated the benefits of massage versus 
simple touch therapy (placing both hands on specific body sites) in 
patients with advanced cancer. This multisite study--conducted at 15 
U.S. hospices in the Population-based Palliative Care Research 
Network--included 380 participants with advanced cancer who were 
experiencing moderate-to-severe pain. Results of the study showed that 
both the massage and simple touch therapy groups experienced 
statistically significant improvements in pain relief, physical and 
emotional distress, and quality of life. Immediate improvement in pain 
and mood was greater with massage than with simple touch; however, 
sustained effects of these therapies were not observed. The researchers 
concluded that massage therapy may provide some immediate relief for 
patients with advanced cancer. They also suggest that simple touch, 
which can be provided by family members and volunteers, may benefit 
these patients. http://nccam.nih.gov/research/results/spotlight/
110608.htm.--Annals of Internal Medicine. 2008;149(6):369-379.
    Study Points to Cost-effectiveness of Naturopathic Care for Low-
Back Pain.--Researchers who studied treatment alternatives for low-back 
pain in a group of 70 warehouse workers found that a naturopathic 
approach (incorporating a range of treatment options--acupuncture, 
exercise and dietary advice, relaxation training, and a back-care 
booklet) was more cost-effective than the employer's usual patient 
education program. Both the workers and the employer benefited from the 
naturopathic approach, which was associated with better health-related 
quality of life, less absenteeism, and lower costs for other treatments 
and pain medication. The study consisted of workers ages 18 to 65 who 
had experienced low-back pain for at least 6 weeks. The workers were 
randomly assigned to receive naturopathic care or patient education 
visits over a 3-month period. The 30-minute, onsite visits were 
conducted semiweekly (naturopathic) or biweekly (patient education). 
The researchers conclude that naturopathic care is more cost-effective 
than a patient education program in treating low-back pain. They also 
recommend further studies of the economic impact of naturopathic 
medicine, particularly to address the limitations of their evaluation. 
http://nccam.nih.gov/research/results/spotlight/070708.htm.--
Alternative Therapies in Health and Medicine. 2008;14(2):32-39.
    Acupuncture Relieves Pain and Improves Function in Knee 
Osteoarthritis.--Acupuncture provides pain relief and improves function 
for people with osteoarthritis of the knee and serves as an effective 
addition to standard care, according to a landmark study. The 
researchers enrolled 570 patients with osteoarthritis of the knee, aged 
50 and older, to receive one of three treatments: acupuncture, 
simulated acupuncture (procedures that mimic acupuncture, sometimes 
also referred to as ``placebo'' or ``sham''), or participation in a 
control group. The control group followed the Arthritis Foundation's 
self-help course for managing their condition over 12 weeks. 
Participants in the actual and simulated acupuncture groups received 23 
treatment sessions over 26 weeks. All study participants continued to 
receive standard medical care from their primary physicians, including 
anti-inflammatory medications and opioid pain relievers. At the start 
of the study, participants' pain and knee function were assessed using 
standard arthritis research survey instruments and measurement tools. 
After 26 weeks participants in the acupuncture group had a 40 percent 
decrease in pain and a nearly 40 percent improvement in function 
compared to their assessments at the start of the study. Findings from 
this study begin to shed more light on acupuncture's possible 
mechanisms and potential benefits, especially in treating painful 
conditions such as arthritis. http://nccam.nih.gov/research/results/
spotlight/052504.htm.--Annals of Internal Medicine. 2004;141(12):901-
910.

Stress/Anxiety
    Long-term Yoga Practice May Decrease Women's Stress.--Research has 
shown that women who practice hatha yoga (a common type of yoga 
involving body postures, breath control, and meditation) regularly 
recover from stress faster than women who are considered yoga 
``novices.'' The research also showed that yoga may boost the mood of 
both yoga experts and novices. The researchers found that the novices' 
blood had 41 percent higher levels of the cytokine interleukin-6 (IL-6) 
than those of the experts. IL-6 is a stress-related compound that is 
thought to play a role in certain conditions such as cardiovascular 
disease and type 2 diabetes. In addition, the novices' levels of C-
reactive protein, which serves as a general marker for inflammation, 
were nearly five times that of the yoga experts. Experts had lower 
heart rates in response to stress events than novices. The researchers 
suggested that this study offers insight into how yoga and its related 
practices may affect health. Regularly performing yoga could have 
health benefits, which may only become evident after years of practice. 
http://nccam.nih.gov/research/results/spotlight/051510.htm.--
Psychosomatic Medicine. Feb 2010;72(2):113-121.
    A Form of Acupuncture May Help in Opioid Addiction.--Transcutaneous 
electric acupoint stimulation (TEAS), a form of acupuncture that uses 
skin electrodes to apply electrical stimulation at different points on 
the body, may help people addicted to opioid drugs. This study, 
supported in part by the NCCAM, also suggests that combining this 
technique with prescribed drugs that ease withdrawal symptoms may 
improve other outcomes for people addicted to opioids. Further, 
participants who received active TEAS were more than two times less 
likely to have used any drugs than those who received simulated TEAS. 
In addition, patients in the active TEAS group reported they were less 
bothered by pain and that they experienced greater improvements in 
overall health. However, the researchers noted that drug abstinence may 
have contributed to these improvements. The researchers noted several 
limitations of this study, including a small number of participants and 
brief duration of treatment. Despite these limitations, they suggested 
that additional studies with larger, more diverse populations and 
longer treatment durations are needed. http://nccam.nih.gov/research/
results/spotlight/010410.htm.--Journal of Substance Abuse Treatment. 
2010;38(1):12-21.
    Transcendental Meditation Helps Young Adults Cope With Stress.--A 
study found that Transcendental Meditation (TM) helped college students 
decrease psychological distress and increase coping ability. For a 
group of students at high risk for developing hypertension, these 
changes also were associated with decreases in blood pressure. Compared 
with controls, the TM group had significant improvement in total 
psychological distress, anxiety, depression, anger/hostility, and 
coping ability. Changes in psychological distress and coping paralleled 
changes in blood pressure. According to the researchers, these findings 
suggest that young adults at risk of developing hypertension may be 
able to reduce that risk by practicing TM. The researchers recommend 
that future studies of TM in college students evaluate long-term 
effects on blood pressure and psychological distress. http://
nccam.nih.gov/research/results/spotlight/051410.htm.--American Journal 
of Hypertension. Dec 2009;22(12):1326-1331.
    Mantram Instruction May Help HIV-positive Individuals Handle 
Stress.--Repeating a mantram (also known as a mantra--the practice of 
silently focusing on a spiritual word or phrase frequently throughout 
the day)--may help HIV-positive individuals develop coping skills and 
reduce anger. Researchers analyzed the effects of a group-based mantram 
training program, based on data from a study involving 93 HIV-positive 
individuals. After the 5-week intervention, the mantram group reported 
a significant increase (25 percent on average) in use of positive 
reappraisal coping (handling stressful situations by focusing on 
positive aspects), while the control group reported a significant 
decrease. At a 22-week followup, anger levels had decreased in the 
mantram group (13 percent on average) but not in the control group. 
According to the researchers, these findings suggest that repeating a 
mantram may help HIV-positive individuals examine stressful situations 
in a more nonjudgmental and accepting way, reducing the likelihood of 
an angry response. This is significant because reducing reactive anger 
may help individuals preserve supportive social relationships as well 
as maintain adherence to antiretroviral treatments. The researchers 
suggested additional studies to explore the effects of mantram on 
attention, cognitive processing, and acceptance-based responding. 
http://nccam.nih.gov/research/results/spotlight/010609.htm.--
International Journal of Behavioral Medicine. 2009;16(1):74-80.
    Stress Management Interventions May Enhance Immune Function in 
People With HIV.--Stress management interventions may help to improve 
immune function and coping skills in HIV-positive individuals. 
Researchers assessed three interventions: cognitive-behavioral 
relaxation training (physical and mental relaxation techniques and 
active coping skills); focused tai chi training (exercises for balance, 
breathing, posturing and movement, and relaxation); and spiritual 
growth (discussions and personal journals to enhance spiritual 
awareness). None of the intervention groups differed from controls on 
measures of HIV-related psychological distress, quality of life, and 
health status, or on physiological stress response (cortisol levels). 
However, compared with controls, all three treatment groups had 
significant increases in lymphocyte proliferation (production of white 
blood cells), indicating enhanced immune function. The researchers 
noted the potentially important clinical implications of this finding. 
They recommend additional research to examine specific effects of 
stress management interventions in people with HIV. http://
nccam.nih.gov/research/results/spotlight/060208.htm.--Journal of 
Consulting and Clinical Psychology. 2008;76(3):431-441.
    Acupuncture May Help Symptoms of Post-traumatic Stress Disorder.--A 
pilot study shows that acupuncture may help people with post-traumatic 
stress disorder. Post-traumatic stress disorder (PTSD) is an anxiety 
disorder that can develop after exposure to a terrifying event or 
ordeal in which grave physical harm occurred or was threatened. 
Traumatic events that may trigger PTSD include violent personal 
assaults, natural or human-caused disasters, accidents, or military 
combat. Researchers conducted a clinical trial examining the effect of 
acupuncture on the symptoms of PTSD. The researchers analyzed 
depression, anxiety, and impairment in 73 people with a diagnosis of 
PTSD. The participants were assigned to receive either acupuncture, 
group cognitive-behavioral therapy, or were put on the wait list as a 
control group. The people in the control group were offered treatment 
or referral for treatment at the end of their participation. The 
researchers found that acupuncture provided treatment effects similar 
to group cognitive-behavioral therapy; both interventions were superior 
to the control group. Additionally, treatment effects of both the 
acupuncture and the group therapy were maintained for 3 months after 
the end of treatment. The limitations are that the study consisted of a 
small group of participants that lacked diversity and that the results 
do not account for outside factors that may have affected the 
treatments' results. http://nccam.nih.gov/research/results/spotlight/
092107.htm.--The Journal of Nervous and Mental Disease, June 2007.
    Self-hypnosis Beneficial for Women Undergoing Breast Biopsy.--
Researchers have found that women who used self-hypnosis during a type 
of core needle breast biopsy experienced anxiety relief and reduced 
pain when compared with standard care. A large core needle breast 
biopsy is usually an outpatient procedure that limits the use of 
anesthetic. Women having this procedure often experience anxiety 
because of the possibility of a cancer diagnosis in addition to the 
anxiety that patients typically experience during a medical procedure. 
In this randomized, controlled trial researchers recruited 236 women 
who were randomly assigned to receive standard care, structured 
empathic attention from a research assistant, or guided self-hypnotic 
relaxation during the biopsy. The study found that both self-hypnosis 
and empathic attention reduced pain and anxiety during the procedure. 
Self-hypnosis provided greater anxiety relief than empathic attention. 
Neither intervention increased procedure time or significantly 
increased cost. As a result, the researchers suggest that self-hypnosis 
appears attractive for outpatient pain management. http://
nccam.nih.gov/research/results/spotlight/122606.htm.--Pain, December 
2006.

            Basic and Translational Research

    Basic and translational research provides important insights into 
how CAM interventions can benefit human health. For example, animal 
studies help to identify biomarkers or signatures of biological effects 
that can be applied to future studies in humans.
    Mindfulness Meditation is Associated With Structural Changes in the 
Brain.--Practicing mindfulness meditation appears to be associated with 
measurable changes in the brain regions involved in memory, learning, 
and emotion, according to a research study that compared brain images 
of participants who participated in a mindfulness-based stress 
reduction program with those who did not. Specifically brain images in 
the meditation group revealed increases in gray matter concentration in 
the left hippocampus, which is an area of the brain involved in 
learning, memory, and emotional control, and is suspected of playing a 
role in producing some of the positive effects of meditation. The 
researchers concluded that these findings may represent an underlying 
brain mechanism associated with mindfulness-based improvements in 
mental health. Additional studies are needed to determine the 
associations between specific types of brain change and behavioral 
mechanisms thought to improve a variety of disorders. http://
nccam.nih.gov/research/results/spotlight/012311.htm.--Psychiatry 
Research: Neuroimaging. 2011;191(1):36-43.
    Study Examines the Effects of Swedish Massage Therapy on Hormones, 
Immune Function.--Massage is used for many health purposes, but little 
is known about how it works on a biological level. This study examined 
the effects of one session of Swedish massage therapy--a form of 
massage using long strokes, kneading, deep circular movements, 
vibration, and tapping--on the body's hormonal response and immune 
function. Researchers randomly assigned 53 healthy adults to receive 
one session of either Swedish massage or light touch (in which the 
therapist used only a light touch with the back of the hand). The 
researchers found that participants who received Swedish massage had a 
significant decrease in the hormone arginine-vasopressin (which plays a 
role in regulating blood pressure and water retention) compared with 
those who were treated with light touch. Study data, although 
preliminary data, led the researchers to conclude that a single session 
of Swedish massage produces measurable biological effects and may have 
an effect on the immune system. However, more research is needed to 
determine the specific mechanisms and pathways behind these changes. 
http://nccam.nih.gov/research/results/spotlight/090110.htm.--The 
Journal of Alternative and Complementary Medicine. 2010;16(10):1-10.
    Electroacupuncture Relieves Cancer Pain in Laboratory Rats.--
Electroacupuncture (acupuncture combined with electrical stimulation) 
has been used to treat cancer pain; however, the existing data on its 
efficacy and how it works are unclear. Researchers investigated the 
effects of electroacupuncture on cancer pain in rats and also looked at 
the underlying biomechanisms. The results showed that compared with the 
sham control, electroacupuncture significantly reduced cancer-induced 
bone pain. The researchers also examined the rats spinal cords to see 
whether electroacupuncture affected chemical processes thought to play 
a role in pain. They found that compared with the sham control, 
electroacupuncture inhibited up-regulation of two substances involved 
in these processes: spinal cord preprodynorphin mRNA and dynorphin. In 
a separate experiment, they found that injection of an antiserum 
against dynorphin also inhibited cancer-induced pain in the rats. The 
researchers concluded that electroacupuncture eases cancer pain in 
rats, at least in part by inhibiting spinal dynorphin. They note that 
their findings support the clinical use of electroacupuncture in the 
treatment of cancer pain. http://nccam.nih.gov/research/results/
spotlight/040109.htm.--European Journal of Pain. 2008;12(7):870-878.
    Brain-Imaging Study Explores Analgesic Effect of Acupuncture.--
Researchers used two imaging technologies--functional magnetic 
resonance imaging (fMRI) and positron emission tomography (PET)--to 
investigate how specific areas of the brain might be involved in 
acupuncture analgesia. The imaging results showed acupuncture-related 
changes in both of the brain's pain networks: the lateral network, 
which is associated with sensory aspects of pain perception, and the 
medial network, which is associated with affective aspects. However, 
the fMRI and PET results pointed to different areas in these networks, 
with one exception: both imaging technologies showed changes in the 
right medial orbitofrontal cortex--an indication that this area of the 
brain may be important in acupuncture analgesia. The researchers note 
that their preliminary findings demonstrate that imaging studies using 
more than one imaging technique have potential for clarifying the 
neural mechanisms of acupuncture. They point out that similar studies 
with much larger samples might reveal other areas of the brain where 
fMRI and PET results converge. http://nccam.nih.gov/research/results/
spotlight/121208.htm.--Behavioural Brain Research. 2008;193(1):63-68.
    Green Tea May Help Protect Against Rheumatoid Arthritis.--
Investigators examined the effects of green tea polyphenols on 
rheumatoid arthritis (RA) by using an animal (rat) model. The animals 
consumed green tea in their drinking water (controls drank water only) 
for 1 to 3 weeks before being injected with heat-killed Mycobacterium 
tuberculosis H37Ra to induce arthritis. The researchers found that 
green tea significantly reduced the severity of arthritis. They suggest 
that green tea affects arthritis by causing changes in various 
arthritis-related immune responses--it suppresses both cytokine IL-17 
(an inflammatory substance) and antibodies to Bhsp65 (a disease-related 
antigen), and increases cytokine IL-10 (an anti-inflammatory 
substance). Therefore, they recommend that green tea be further 
explored as a dietary therapy for use together with conventional 
treatment for managing RA. http://nccam.nih.gov/research/results/
spotlight/120808.htm.--The Journal of Nutrition. 2008:138(11):2111-
2116.
    Electroacupuncture May Help Alcohol Addiction.--Researchers 
examined the effects of electroacupuncture on alcohol intake by 
alcohol-preferring rats. After being trained to drink alcohol 
voluntarily and then subjected to alcohol deprivation, the rats 
received either electroacupuncture or sham electroacupuncture, and 
their alcohol intake was monitored after the intervention. Some rats 
were also pretreated with naltrexone (a drug that blocks the effects of 
opiates), so researchers could look for evidence that opiate mechanisms 
are involved in electroacupuncture's effects. The results showed that 
electroacupuncture reduced the rats' alcohol intake. The researchers 
also found that injecting the rats with naltrexone blocked the effect 
of electroacupuncture on alcohol intake-an indication that this effect 
may be through the brain's opiate system. On the basis of their 
findings, the researchers recommend rigorous clinical trials to study 
the effects of electroacupuncture in alcohol-addicted people. They also 
recommend further investigation of how electroacupuncture affects the 
brain. http://nccam.nih.gov/research/results/spotlight/022609.htm.--
Neurochemical Research. 2008;33(10):2166-2170.
    Lifestyle Changes May Affect Cell-level Processes Related to 
Disease.--Disease risk, progression, and premature mortality--in many 
types of cancer and in cardiovascular and infectious diseases--have 
been linked to telomeres, which are protective DNA-protein complexes 
that keep cells genetically stable. The cellular enzyme telomerase is 
an important part of the body's maintenance system for these essential 
complexes. In a pilot study researchers investigated the effects of 
lifestyle changes on telomerase levels in 24 men with low-risk prostate 
cancer. The participants underwent a comprehensive lifestyle 
modification that included: improved nutrition, moderate aerobic 
exercise, stress management, and increased social support. After 3 
months, the study participants' telomerase activity had increased 29.8 
percent. Decreases in psychological distress and low-density 
lipoprotein (LDL) cholesterol were associated with the increase in 
telomerase activity. This is the first longitudinal study to suggest 
that lifestyle modifications (or any intervention) might significantly 
increase telomerase activity. The researchers emphasize that additional 
research is needed and recommend larger randomized controlled trials to 
confirm the findings. http://nccam.nih.gov/research/results/spotlight/
100908.htm. The Lancet Oncology. Published online September 16, 2008.--
Journal of Immunology. 2007;179(6):4249-4254.
    New Research Gives Insight Into How Acupuncture May Relieve Pain.--
In the first study of its kind, researchers evaluated the effects of 
acupuncture on brain activity following active stimulation. The 
researchers used functional magnetic resonance imagery (fMRI) to 
monitor brain activity in 15 healthy adults before and after true 
acupuncture and sham acupuncture. The procedure lasted 150 seconds, and 
the rest period was 5.5 minutes. Analysis of the fMRI images showed 
that following true acupuncture--but not sham--there were increased 
connections among the parts of the brain involved in the perception and 
memory of pain. The subjects also reported stronger sensations with 
true acupuncture than with sham. The researchers concluded that 
acupuncture changes resting-state brain activity in ways that may 
account for its analgesic and other therapeutic effects. http://
nccam.nih.gov/research/results/spotlight/111408.htm.--Pain. 
2008;136(3):407-418.
    Prostate Genes Altered by Intensive Diet and Lifestyle Changes.--A 
pilot study suggests that intensive lifestyle and diet changes may 
alter gene expression (the way a gene acts) in the prostate--possibly 
affecting the progression of prostate cancer. This pilot study included 
a group of 31 men with low-risk prostate cancer. These men declined 
immediate surgery, hormonal therapy, or radiation, and participated in 
an intensive 3-month nutritional and lifestyle intervention while 
researchers monitored their tumor progression. The men stuck to a low-
fat, plant-based diet and took dietary supplements including fish oil, 
selenium, and vitamins C and E. They also participated in stress 
management activities, did moderate aerobic exercise, and attended 
group support sessions. The researchers found that there were changes 
in the men's RNA following the lifestyle and diet modifications. 
Certain RNA transcripts that play a critical role in tumor formation 
had ``up-regulated'' (increased) and others ``down-regulated'' 
(decreased). The researchers concluded that intensive nutrition and 
lifestyle changes may alter gene expression in the prostate. They 
believe that understanding how these changes affect the prostate may 
lead to more effective prevention and treatment for prostate cancer, 
and recommend larger, randomized controlled trials to confirm the 
results of this pilot study. http://nccam.nih.gov/research/results/
spotlight/100808.htm.--Proceedings of the National Academy of Sciences 
of the United States of America. 2008;105(24):8369-8374.
    Meditation May Increase Empathy.--Previous brain studies have shown 
that when a person witnesses someone else in an emotional state--such 
as disgust or pain--similar activity is seen in both people's brains. 
This shows a physiological base for empathy, defined as the ability to 
understand and share another person's experience. Now, research using 
advanced brain images (functional magnetic resonance imaging) have 
shown that compassion meditation--a specific form of Buddhist 
meditation--may increase the human capacity for empathy. In the study, 
researchers compared brain activity in meditation experts with that of 
subjects just learning the technique (16 in each group). They measured 
brain activity during meditation and at rest, in response to sounds 
designed to evoke a negative, positive, or neutral emotional response. 
The researchers found that both the novice and the expert meditators 
showed an increased empathy reaction when in a meditative state. 
However, the expert meditators showed a much greater reaction, 
especially to the negative sound, which may indicate a greater capacity 
for empathy as a result of their extensive meditation training. An 
increased capacity for empathy, the authors say, may have clinical and 
social importance. The next step, they add, is to investigate whether 
compassion meditation results in more altruistic behavior or other 
changes in social interaction. http://nccam.nih.gov/research/results/
spotlight/060608.htm.--PLoS ONE [online journal], 2008.
    Meditation May Make Information Processing in the Brain More 
Efficient.--``Attentional-blink'' occurs when two pieces of information 
are presented to a person in very close succession, and the brain 
doesn't perceive the second piece of information because it is still 
processing the first. Researchers attempted to determine if intensive 
mental training through meditation could extend the brain's limits on 
information processing, reducing ``attentional-blink.'' Two groups of 
people--17 expert meditators and 23 novices--were compared to see if 
either was better at recognizing two pieces of information shown in 
quick succession. The participants were tested at the beginning and end 
of a 3-month period. For the intervening 3 months, the meditation 
practitioners participated in a retreat, during which they meditated 
for 10-12 hours a day. The novices participated in a 1-hour meditation 
class, and were asked to meditate for 20 minutes a day for the week 
before each test. The researchers found that intensive training did 
reduce ``attentional-blink.'' The participants who had gone through the 
mental training were more likely to perceive both pieces of information 
instead of just the first because the brain used fewer resources to 
detect the first piece of information--leaving more resources available 
to detect the second. The researchers also note that this study 
supports the idea that brain plasticity, or the ability of the brain to 
adapt, exists throughout life. http://nccam.nih.gov/research/results/
spotlight/082307.htm.--PLOS Biology, June 2007.

            Quality of Life and Other Factors

    Quality of Life and Safety of Tai Chi and Green Tea Extracts in 
Postmenopausal Women.--For postmenopausal women with osteopenia (low 
bone mineral density), practicing tai chi and/or taking green tea 
polyphenols appears to be safe. Further, practicing tai chi by itself 
or in combination with green tea polyphenol supplements may improve 
quality of life; however, taking green tea supplements by themselves 
has no significant improvement in quality of life. The researchers 
noted that this is the first placebo-controlled, randomized study to 
evaluate the safety of long-term use of green tea supplements in 
postmenopausal women. Based on these findings, the researchers 
concluded that green tea polyphenols at a dose of 500 mg daily for 24 
weeks, alone or in combination with tai chi, appears to be safe in 
postmenopausal women with low bone mineral density. http://
nccam.nih.gov/research/results/spotlight/121410.htm.--BMC Complementary 
and Alternative Medicine. 2010;10(1):76. [Epub ahead of print]
    Tai Chi and Qi Gong Show Some Beneficial Health Effects.--A review 
of scientific literature suggests that there is strong evidence of 
beneficial health effects of tai chi and qi gong, including for bone 
health, cardiopulmonary fitness, balance, and quality of life. Both tai 
chi and qi gong (also known as qigong) have origins in China and 
involve physical movement, mental focus, and deep breathing. 
Researchers analyzed 77 articles reporting the results of 66 randomized 
controlled trials of tai chi and qi gong. The studies involved a total 
of 6,410 participants. Of the many outcomes identified by the 
reviewers, current research suggests that the strongest and most 
consistent evidence of health benefits for tai chi or qi gong is for 
bone health, cardiopulmonary fitness, balance and factors associated 
with preventing falls, quality of life, and self-efficacy (the 
confidence in and perceived ability to perform a behavior). The 
reviewers concluded that the evidence is sufficient to suggest that tai 
chi and qi gong are a viable alternative to conventional forms of 
exercise. http://nccam.nih.gov/research/results/spotlight/071910.htm.--
American Journal of Health Promotion. 2010;24(6):e1-e25.
    Hypnosis May Reduce Hot Flashes in Breast Cancer Survivors.--
Researchers investigated the effects of hypnosis on hot flashes among 
women with a history of primary breast cancer, no current evidence of 
detectable disease, and at least 14 hot flashes per week over a 1-month 
period. Sixty women were assigned to receive either hypnosis (weekly 
50-minute sessions, plus instructions for at-home self-hypnosis) or no 
treatment. The women who received hypnosis had a 68-percent reduction 
in self-reported hot flash frequency/severity and experienced an 
average of 4.39 fewer hot flashes per day. Compared with controls, they 
also had significant improvements in self-reported anxiety, depression, 
interference with daily activities, and sleep. The researchers 
concluded that hypnosis appears to reduce perceived hot flashes in 
breast cancer survivors and may have additional benefits such as 
improved mood and sleep. They recommend long-term, randomized, placebo-
controlled studies to further explore the benefits of hypnosis for 
breast cancer survivors. The researchers are currently conducting a 
randomized clinical trial with 200 participants. http://nccam.nih.gov/
research/results/spotlight/102308.htm.--Journal of Clinical Oncology. 
Published online September 22, 2008.
    Tai Chi May Help Heart Failure Patients Sleep Better.--People with 
heart failure may benefit from practicing tai chi, according to 
researchers who analyzed sleep in 18 patients with chronic heart 
failure. All patients were on maximal medical therapy. The patients 
were assigned into one of two groups: a usual care group (the control) 
that received medication and diet/exercise counseling, or a tai chi 
group that received usual care plus 12 weeks of tai chi training. 
Compared with the usual care group, the tai chi group had significant 
improvements in sleep stability. The tai chi group also demonstrated 
significant quality-of-life improvements over the usual care group. The 
researchers concluded that a 12-week tai chi exercise program may help 
heart failure patients sleep better. They noted that it remains to be 
determined if any single component of tai chi--meditation, relaxation, 
or physical activity--may be responsible for the observed benefit. They 
suggested further research to better understand the mechanisms of tai 
chi's effects on sleep should include more conventional sleep testing 
to document sleep stages and patterns of sleep disruption. http://
nccam.nih.gov/research/results/spotlight/072508.htm.--Sleep Medicine. 
2008;9(5):527-536.
    Tai Chi Chih Improves Sleep Quality in Older Adults.--Researchers 
conducted a randomized controlled trial to determine whether tai chi 
chih could improve sleep quality in healthy, older adults with moderate 
sleep complaints. In the study, 112 individuals aged 59 to 86 
participated in either tai chi chih training or health education 
classes for 25 weeks. Participants rated their sleep quality based on 
the Pittsburgh Sleep Quality Index, a self-rate questionnaire that 
assesses sleep quality, duration, and disturbances. The results of the 
study showed that the people who participated in tai chi chih sessions 
experienced slightly greater improvements in self-reported sleep 
quality. The researchers concluded that tai chi chih can be a useful 
nonpharmacologic approach to improving sleep quality in older adults 
with moderate sleep complaints, and may help to prevent the onset of 
insomnia. http://nccam.nih.gov/research/results/spotlight/031109.htm.--
Sleep. 2008;31(7):1001-1008.
    Acupuncture Shows Promise in Improving Rates of Pregnancy Following 
IVF.--A review of seven clinical trials of acupuncture given with 
embryo transfer in women undergoing in vitro fertilization (IVF) 
suggests that acupuncture may improve rates of pregnancy. An estimated 
10 to 15 percent of couples experience reproductive difficulty and seek 
specialist fertility treatments, such as IVF. According to researchers 
who conducted the systematic review, acupuncture has been used in China 
for centuries to regulate the female reproductive system. With this in 
mind, the reviewers analyzed results from seven clinical trials of 
acupuncture in women who underwent IVF to see if rates of pregnancy 
were improved with acupuncture. The studies encompassed data on over 
1,366 women and compared acupuncture, given within 1 day of embryo 
transfer, with sham acupuncture, or no additional treatment. The 
reviewers found that acupuncture given as a complement to IVF increased 
the odds of achieving pregnancy. According to the researchers, the 
results indicate that 10 women undergoing IVF would need to be treated 
with acupuncture to bring about one additional pregnancy. The results, 
considered preliminary, point to a potential complementary treatment 
that may improve the success of IVF and the need to conduct additional 
clinical trials to confirm these findings. http://nccam.nih.gov/
research/results/spotlight/020808.htm.--British Medical Journal. 
Published online February 2008.
    Tai Chi May Help Maintain Bone Mineral Density in Postmenopausal 
Women.--Tai chi may be a safe alternative to conventional exercise for 
maintaining bone mineral density (BMD) in postmenopausal women. Bone 
mineral density is one of the key indicators of bone strength and low 
BMD is associated with osteoporosis. Exercise is an important component 
of osteoporosis prevention and treatment. Researchers conducted a 
systematic review of research looking at the effect of tai chi, a mind-
body practice that originated in China, on BMD. They found that tai chi 
may be an effective, safe, and practical intervention for maintaining 
BMD in postmenopausal women. The authors further note that the benefits 
of tai chi appeared similar to those of conventional exercise. However, 
tai chi may also improve balance, reduce fall frequency, and increase 
musculoskeletal strength. They note that the evidence is preliminary 
because the research they reviewed was of limited scope and quality, 
but enough evidence of effectiveness exists to warrant further 
research. http://nccam.nih.gov/research/results/spotlight/081407.htm. 
Archives of Physical Medicine and Rehabilitation, May 2007.
    Tai Chi Boosts Immunity to Shingles Virus in Older Adults.--Tai 
chi, a traditional Chinese form of exercise, may help older adults 
avoid getting shingles by increasing immunity to varicella-zoster virus 
and boosting the immune response to varicella vaccine. The study is the 
first rigorous clinical trial to suggest that a behavioral 
intervention, alone or together with a vaccine, can help protect older 
adults from the varicella virus, which causes both chickenpox and 
shingles. The randomized, controlled trial included 112 healthy adults 
ages 59 to 86. Each person took part in a 16-week program of either tai 
chi or health education with 120 minutes of instruction weekly. After 
the tai chi and health education programs, with periodic blood tests to 
determine levels of varicella virus immunity, people in both groups 
received a single injection of the chickenpox vaccine, VARIVAX. Nine 
weeks later, the investigators assessed each participant's level of 
varicella immunity and compared it to immunity at the start of the 
study. Tai chi alone was found to increase participants' immunity to 
varicella, and tai chi combined with the vaccine produced a 
significantly higher level of immunity, about a 40 percent increase, 
over the vaccine alone. The study also showed that the tai chi group's 
rate of increase in immunity over the course of the study was double 
that of the health education group. Finally, the tai chi group reported 
significant improvements in physical functioning, bodily pain, vitality 
and mental health. http://nccam.nih.gov/research/results/spotlight/
040607.htm.--Journal of the American Geriatrics Society, April 2007.
    Study Compares Year-long Effectiveness of Four Weight-loss Plans.--
The very low carbohydrate diet known as the Atkins diet may contribute 
to greater weight loss than higher carbohydrate plans without negative 
effects such as increased cholesterol. The study consisted of 311 
premenopausal women, all of whom were overweight or obese who were 
randomly assigned to 1 of 4 diets. Each of the diets used were selected 
for their different levels of carbohydrate consumption: the Atkins 
diet, the Zone diet, the LEARN diet and the Ornish diet. Participants 
in each group received books that accompanied their assigned diet plan, 
and attended hour-long classes with a registered dietitian once a week 
for the first 8 weeks. The researchers recorded body mass index (BMI); 
percent body fat; waist-hip ratio; as well as metabolic measures such 
as, insulin, cholesterol, glucose, triglyceride, and blood pressure 
levels. The Atkins diet group reported the most weight loss at 12 
months with an average loss of just over 10 pounds. They also had more 
favorable overall metabolic effects. Average weight loss across all 
four groups ranged from 3.5 to 10.4 pounds. The authors note that 
``even modest reductions in excess weight have clinically significant 
effects on risk factors such as triglycerides and blood pressure.'' 
http://nccam.nih.gov/research/results/spotlight/030607.htm.--Journal of 
the American Medical Association. March 2007.

Natural Products Interventions
            Treatment or Enhancement of Treatment
    New Approach for Peanut Allergy in Children Holds Promise.--
Currently, there are no treatments available for people with peanut 
allergy. A new treatment may be a safe and effective form of 
immunotherapy for those children. The double-blind, placebo-controlled 
study investigated the safety, clinical effectiveness, and immunologic 
changes with sublingual immunotherapy--a treatment that involves 
administering very small amounts of the allergen extract under a 
person's tongue. Though these findings are promising, more study is 
needed to determine whether sublingual immunotherapy can increase long-
term tolerance to peanuts in children with peanut allergy. http://
nccam.nih.gov/research/results/spotlight/022011.htm.--The Journal of 
Allergy and Clinical Immunology. 2011.
    Magnesium Supplements May Benefit People With Asthma.--Some 
previous studies have reported associations between low magnesium 
consumption and the development of asthma. This study provides 
additional evidence that adults with mild-to-moderate asthma may 
benefit from taking magnesium supplements. Researchers found that 
participants who took magnesium experienced significant improvement in 
lung activity and the ability to move air in and out of their lungs. 
Those taking magnesium also reported other improvements in asthma 
control and quality of life compared with people who received placebo. 
The researchers noted that this study adds to the body of research that 
shows subjective and objective benefits of magnesium supplements in 
people with mild-to-moderate asthma. http://nccam.nih.gov/research/
results/spotlight/021110.htm.--Journal of Asthma. 2010;47(1):83-92.
    Study Shows Chamomile Capsules Ease Anxiety Symptoms.--Researchers 
conducted a randomized, double-blind, placebo-controlled trial to test 
the effects of chamomile extract in patients diagnosed with mild to 
moderate generalized anxiety disorder (GAD). Researchers used the 
Hamilton Anxiety Rating (HAM-A) and other tests to measure changes in 
anxiety symptoms over the course of the study; dosage adjustments were 
based on HAM-A scores. Compared with placebo, chamomile was associated 
with a greater reduction in mean HAM-A scores--the study's primary 
outcome measure. The difference was clinically meaningful and 
statistically significant. Chamomile also compared favorably with 
placebo on other outcome measures (although the differences were not 
statistically significant), and was well tolerated by participants. 
These results suggest that chamomile may have modest benefits for some 
people with mild to moderate GAD. As this was the first controlled 
trial of chamomile extract for anxiety, the researchers note that 
additional studies using larger samples and studying effects for longer 
periods of time would be helpful. They also point out that other 
chamomile species, preparations (e.g., extracts standardized to 
constituents other than apigenin), and formulations (e.g., oil or tea) 
might produce different results. http://nccam.nih.gov/research/results/
spotlight/040310.htm.--Journal of Clinical Psychopharmacology. 2009 
Aug;29(4):378-382.
    Study Indicates Cranberry Juice Does Not Interfere With Two 
Antibiotics Women Take for Recurrent Urinary Tract Infections.--
Cranberry juice, a popular home remedy for urinary tract infections 
(UT), is often taken along with low-dose antibiotics as a preventive 
measure. Because little is known about the potential of cranberry juice 
to interact with drugs, researchers studied cranberry's effects on two 
antibiotics frequently prescribed for UTI: amoxicillin and cefaclor. 
The data showed that cranberry juice did not significantly affect 
either antibiotic's oral absorption or renal clearance (i.e., how 
completely the body processed the drugs in the intestine and kidneys). 
Absorption took somewhat longer with cranberry juice, but the delay was 
small, and the total amount of antibiotic absorbed was not affected. 
Based on these results, the researchers concluded that cranberry juice 
cocktail, consumed in usual quantities, is unlikely to change the 
effects of these two antibiotics on UTIs. They noted that the same may 
or may not be true of other antibiotics, or when people who take 
antibiotics also drink a large quantity of concentrated cranberry 
juice. http://nccam.nih.gov/research/results/spotlight/081009.htm.--
Antimicrobial Agents and Chemotherapy. 2009 Jul;53(7):2725-32.
    Traditional Chinese Herbs May Benefit People With Asthma.--
Scientists reviewed research evidence on traditional Chinese medicine 
(TCM) herbs for asthma, focusing on studies reported since 2005. They 
determined that preliminary clinical trials of formulas containing 
Radix glycyrrhizae in combination with various other TCM herbs have had 
positive results. Laboratory findings on TCM herbal remedies suggest 
several possible mechanisms of action against asthma, including an 
anti-inflammatory effect, inhibition of smooth-muscle contraction in 
the airway, and modulation of immune system responses. http://
nccam.nih.gov/research/results/spotlight/061609.htm.--Journal of 
Allergy and Clinical Immunology. 2009;123(2):297-306.
    A Review of St. John's Wort Extracts for Major Depression.--
Researchers reviewed the scientific literature on St. John's wort for 
major depression and analyzed findings from randomized, double-blind 
studies comparing St. John's wort extracts with placebo and standard 
antidepressants. The researchers reviewed a total of 29 studies in 
5,489 people. The studies came from a variety of countries, tested 
several different St. John's wort extracts, and mainly included people 
with minor to moderately severe symptoms of depression. According to 
this literature review, St. John's wort extracts appeared to be 
superior to placebo, were as effective as standard antidepressants, and 
had fewer side effects than antidepressants. However, the findings from 
studies in German-speaking countries were disproportionately favorable, 
possibly because some subjects had slightly different types of 
depression, or because some of the small studies were flawed and overly 
optimistic in reporting their results. The authors noted the need to 
investigate the reasons for the differences between study findings from 
German-speaking countries and those from other countries. http://
nccam.nih.gov/research/results/spotlight/120908.htm.--Cochrane Database 
of Systematic Reviews. 2008 8;(4):CD000448.
    Study Suggests Vitamin E May Help People With Asthma.--A form of 
vitamin E (gamma-tocopherol) commonly found in foods may be a useful 
additional treatment for asthma, according to preliminary research. 
Researchers investigated the biological activity of a gamma-tocopherol 
supplement in asthma patients. The researchers gave a daily dose of a 
vitamin E preparation rich in gamma-tocopherol to 16 volunteers. Eight 
healthy volunteers and eight volunteers with allergic asthma received 
one supplement daily during the first week, followed by a week with no 
treatment, and then two supplements daily for another week. They found 
similar results for both doses--the vitamin E supplements prevented 
inflammation and decreased oxidative stress without any adverse health 
effects. This research was an initial step in extending previous 
findings of gamma-tocopherol's anti-inflammatory effects in animals. 
Further research on vitamin E in patients with asthma is under way. 
http://nccam.nih.gov/research/results/spotlight/070208.htm.--Free 
Radical Biology & Medicine. 2008;45(1):40-49.
    Omega-3 Fatty Acids May Be Helpful in Psychiatric Care.--Omega-3 
fatty acids may hold promise for use in psychiatry, particularly for 
depression and bipolar disorder. Researchers conducted a meta-analysis 
of research looking at omega-3 fatty acid supplements as treatments for 
psychiatric conditions, such as depression, bipolar disorder, 
schizophrenia, dementia, and attention-deficit hyperactivity disorder. 
Omega-3 fatty acids are essential nutrients that the body cannot make 
on its own, so they must come from food sources. The richest source of 
these fatty acids is fish and seafood, but they can also be found in 
flaxseeds and some eggs. The authors suggest that omega-3 supplements 
may be helpful for people with depression or bipolar disorder as a 
complement to standard care. However, they were unable to determine 
benefits for other conditions such as schizophrenia and dementia. They 
also ``strongly recommend that patients with psychiatric disorders 
should not elect supplementation with omega-3 fatty acids in lieu of 
established psychiatric treatment options.'' They further recommend 
studies to look at how the nutrient may work, and large trials to 
conclusively determine the utility of omega-3 fatty acids in 
psychiatric care. http://nccam.nih.gov/research/results/spotlight/
121506.htm.--Journal of Clinical Psychiatry, December 2006.
    Polyunsaturated Fatty Acids for Depression.--Omega-6 and omega-3 
fatty acids (also called PUFAs, short for polyunsaturated fatty acids) 
are among the CAM therapies used with the intent to help symptoms of 
depression. A team reviewing the evidence found five randomized 
controlled trials to be of sufficient quality for review, although all 
were small and of short duration. All but one of these trials found 
some improvement from using PUFAs for symptoms of depression, 
particularly from omega-3 fatty acids. The authors concluded that while 
the evidence to support using PUFA supplements as a treatment for 
depression is not strong, enough potential exists to merit further 
research. http://nccam.nih.gov/research/results/spotlight/050106.htm.--
Journal of Affective Disorders, May 2006.

            Disease Prevention

    Ginkgo Does Not Shield Seniors' Hearts, But It May Protect Their 
Leg Arteries.--While findings from the Ginkgo Evaluation of Memory 
(GEM) study show that the herbal supplement Ginkgo biloba did not 
prevent heart attack, stroke, or death in a group of older adults, the 
herb may reduce the risk of developing peripheral arterial disease 
(also known as peripheral vascular disease), a painful and potentially 
life-threatening condition affecting blood circulation in the legs, 
arms, stomach, and kidneys. Of the 35 cases of peripheral arterial 
disease observed in the study, 23 patients received placebo and 12 
patients received ginkgo, a difference that was statistically 
significant. The researchers reported that this finding was consistent 
with European studies that reported improvements in patients with 
peripheral arterial disease who received ginkgo versus placebo. But, 
due to the small number of patients in whom this was seen, the 
researchers suggest larger trials to evaluate the herb before they 
would recommend it as a treatment for peripheral arterial disease. This 
study was a planned secondary outcome of the GEM study. http://
nccam.nih.gov/research/results/spotlight/052110.htm.--Circulation: 
Cardiovascular Quality and Outcomes. 2010;3(1):41-47.
    Chinese Herbal Medicine May Benefit People With Pre-Diabetes.--In 
China and other Asian countries, Chinese herbal medicines have long 
been used to prevent or delay the onset of diabetes, and there is 
anecdotal evidence regarding efficacy for this purpose. A recent 
review, funded in part by the NCCAM, examined related clinical trials 
to see whether scientific evidence supports recommending Chinese herbal 
medicine as a treatment option for people with pre-diabetes. The review 
looked at 16 clinical trials involving 1,391 participants with pre-
diabetes, 15 different herbal formulations, and various comparisons 
(i.e., lifestyle modification, drug interventions, placebo). Analysis 
of data from eight trials that included lifestyle modification as a 
comparison found that lifestyle modification combined with Chinese 
herbs was twice as effective as lifestyle modification alone in 
normalizing blood sugar levels. Participants who received herbal 
formulations were also less likely to develop full-blown diabetes 
during the study period. Due to limitations among the studies reviewed, 
the reviewers concluded that while their findings are promising, 
further, well-designed trials are needed to clarify the potential role 
of Chinese herbal medicines in glucose control and diabetes prevention. 
http://nccam.nih.gov/research/results/spotlight/110309.htm.--Cochrane 
Database of Systematic Reviews. 2009(4):CD00066690.
    Red Yeast Rice May Help Patients With High Cholesterol Who Cannot 
Take Statin Drugs.--In light of previous findings that red yeast rice 
can reduce levels of low-density lipoprotein (LDL, or ``bad'' 
cholesterol), researchers investigated the effects of this supplement 
in patients with high cholesterol and a history of statin-associated 
myalgia (SAM). Compared with placebo, red yeast rice significantly 
decreased blood levels of LDL and total cholesterol over a 24-week 
period, without increasing the incidence of myalgia. Red yeast rice did 
not significantly affect levels of high-density lipoprotein (HDL, or 
``good'' cholesterol), triglycerides, weight loss, or pain severity. 
This was the first randomized, double-blind, placebo-controlled trial 
to evaluate red yeast rice in patients who cannot take statin drugs 
because of muscle pain. The results suggest that red yeast rice may be 
a cholesterol-lowering alternative for these patients, but additional, 
larger studies are needed to establish long-term safety and efficacy. 
The researchers also suggest studies to compare red yeast rice directly 
with statins and to explore the role of lifestyle change therapy. 
http://nccam.nih.gov/research/results/spotlight/071709.htm.--Annals of 
Internal Medicine. 2009;150(12):830-839.
    Flaxseed Reduces Some Risk Factors of Cardiovascular Disease.--
Flaxseed is rich in alpha linolenic acid (ALA), a plant-based omega-3 
fatty acid, as well as fiber and lignans (phytoestrogens), making it a 
possible functional food for reducing cardiovascular risk factors. A 
double blind, randomized, controlled clinical trial by researchers 
explored the effects of flaxseed on various cardiovascular risk factors 
in adults. Researchers found that flaxseed positively affected 
lipoprotein A and insulin sensitivity. They also found a modest but 
short-lived lowering effect in participants' LDL (``bad'') cholesterol 
levels. However, the researchers also noted that flaxseed significantly 
lowers HDL (``good'') cholesterol levels in men, although not in women. 
There were no changes noted in markers of inflammation or oxidative 
stress. The authors suggest that additional investigation of the HDL 
lowering effect among men may be warranted. http://nccam.nih.gov/
research/results/spotlight/062308.htm.--Nutrition, 2008.

            Basic and Translational Research

    Basic and translational research provides important insights into 
how CAM interventions can benefit human health. For example, animal 
studies help to identify biomarkers or signatures of biological effects 
that can be applied to future studies in humans.
    Laboratory Study Suggests Potential Anti-cancer Benefit of White 
Tea Extract.--White tea extract increased a specific type of cell death 
in laboratory cultures of two different types of nonsmall cell lung 
cancer cells, indicating that the tea may have an anti-cancer effect. 
Although white tea comes from the same plant as green and black teas 
(Camellia sinensis), white tea goes through much less processing, 
resulting in a higher concentration of polyphenols. This study, for the 
first time, showed the roles of the PPAR-gamma and 15-LOX signaling 
pathways in white tea-induced apoptosis. (A reduction in PPAR-gamma in 
a tumor is linked to poor prognosis in patients with lung cancer.) The 
researchers also compared green tea extract with white tea extract and 
found that white tea extract was significantly more effective in 
increasing certain RNA transcripts (e.g., PPAR-gamma) that play a 
critical role in cell death. They noted, however, that the components 
in white tea extract that may be responsible for this outcome are not 
yet known. They noted that the findings from this preliminary study 
provide an important basis for more investigation of the anti-cancer 
properties of white tea extract and whether it may help prevent the 
development of lung cancer. http://nccam.nih.gov/research/results/
spotlight/092110.htm.--Cancer Prevention Research. 2010;3(9):1132-1140.
    Laboratory Study Shows Turmeric May Have Bone-Protective Effects.--
Turmeric--an herb commonly used in curry powders, mustards, and 
cheeses--may protect bones against osteoporosis. This study, which used 
an animal (rat) model of postmenopausal osteoporosis, builds on 
previous laboratory research examining turmeric's anti-arthritic 
properties. Funded in part by the NCCAM, the study tested two turmeric 
extracts containing different amounts of curcuminoids--(components of 
the herb) in female rats whose ovaries had been surgically removed 
(ovariectomy--a procedure that causes changes associated with 
menopause, including bone loss). Tests showed that while nonenriched 
turmeric extract did not have bone-protective effects, curcuminoid-
enriched turmeric extract prevented up to 50 percent of bone loss, and 
also preserved bone structure and connectivity. Other physiological 
changes associated with ovariectomy (weight gain and shrinking of the 
uterus) were unaffected--an indication that the bone-protective effects 
did not involve an estrogen-based chemical pathway. The researchers 
concluded that turmeric may protect bones, but that the effect depends 
on the amount of curcuminoids present. However, they emphasized that 
clinical research is needed to evaluate the use of turmeric-derived 
curcuminoid products to guard against osteoporosis in humans. http://
nccam.nih.gov/research/results/spotlight/093010.htm.--Journal of 
Agricultural and Food Chemistry. 2010;58(17):9498-9504.
    Effects of Milk Thistle Extract on the Hepatitis C Virus 
Lifecycle.--A laboratory study suggests that silymarin--an extract from 
the milk thistle plant--has multiple effects against the lifecycle of 
the hepatitis C virus. Hepatitis C is a chronic (long lasting) disease 
that primarily affects the liver and is often difficult to cure. This 
study examined the antiviral properties and mechanisms of silymarin on 
cultured (grown in a lab) human liver cells infected with the virus. By 
analyzing the interactions between silymarin and the virus, the 
researchers observed that silymarin prevented the entry and fusion of 
the hepatitis C virus into the target liver cells. They also found that 
silymarin inhibited the ability of the virus to produce RNA (a chemical 
that plays an important role in protein synthesis and other chemical 
activities of the cell), interfering with a portion of the virus's 
lifecycle. These findings build on previous research of silymarin's 
antiviral and anti-inflammatory properties and provide more information 
about the potential mechanisms involved in silymarin's antiviral 
actions. Further research, particularly in clinical trials, is needed 
to determine if silymarin could be a safe and effective supplement for 
treating hepatitis C in humans. http://nccam.nih.gov/research/results/
spotlight/061610.htm.--Hepatology. 2010;51(6):1912-1921.
    Fish Oil Enhances Effects of Green Tea on Alzheimer's Disease in 
Mice.--Fish oil, when combined with epigallocatechin-3-gallate (EGCG--a 
polyphenol and antioxidant found in green tea), may affect chemical 
processes in the brain associated with Alzheimer's disease. This study, 
which used an animal (mouse) model of Alzheimer's disease, builds on 
previous research linking the disease to peptides (amino acid chains) 
called beta-amyloids and laboratory studies suggesting that EGCG 
decreases memory problems and beta-amyloid deposits in mice. 
Researchers found that the mice fed the combination of fish oil and 
EGCG had a significant reduction in amyloid deposits that have been 
linked with Alzheimer's disease. Upon examination of blood and brain 
tissues of the mice, the researchers found high levels of EGCG in the 
mice that were fed the combination of fish oil and low-dose EGCG 
compared with those fed low-dose EGCG alone. A possible explanation, 
according to the researchers, is that fish oil enhances the 
bioavailability of EGCG--that is, the degree to which EGCG was absorbed 
into the body and made available to the brain. This effect, in turn, 
may contribute to the increased effectiveness of this combination. 
Further research is necessary, however, to determine if the combination 
of fish oil and EGCG affects memory or cognition, and whether it might 
have potential as an option for people at risk of developing 
Alzheimer's disease. http://nccam.nih.gov/research/results/spotlight/
031610.htm.--Neuroscience Letters. 2010;471(3):134-138.
    Laboratory Study Suggests Potential Anti-Cancer Benefit of 
Ginseng.--American ginseng (Panax quinquefolius) extract caused 
laboratory cultures of colorectal cancer cells to die, indicating that 
the herb may have an anti-cancer effect. Although results from the 
study suggest that combining ginseng with antioxidants such as vitamin 
C may potentially enhance this effect, there is no evidence yet that 
this laboratory research can be extended to treatments in people. 
Researchers treated two types of colorectal cancer cells with steamed 
American ginseng root extract. This caused damage to the cells' 
mitochondria, the internal structures that are involved with energy 
production, and led to apoptosis (cell death). It also increased levels 
of reactive oxygen species (ROS)--a byproduct of the processes in which 
cells use and break down oxygen (increased levels of ROS can either 
bring on cell death or activate the survival pathways that protect 
against it). Whether ROS acts to induce cell death or survival in 
response to ginseng depends on the specific biochemical pathways that 
are activated, and how this happens remains unknown. Further studies 
are needed. The researchers also noted the need for additional 
investigations to test whether combining ginseng and antioxidants might 
help prevent the development of colorectal cancers. http://
nccam.nih.gov/research/results/spotlight/032510.htm.--Cancer Letters. 
2010;289(1):62-70.
    Mouse Study Shows Green Tea Polyphenols May Repair DNA Damage 
Caused by Ultraviolet (UV) Radiation.--Antioxidants found in green tea 
may help repair DNA damage caused by sun exposure, according to a 
recent study in mice. Exposure to UV radiation can damage DNA and, in 
turn, trigger suppression of the immune system--a risk factor for 
developing skin cancer. The study, funded in part by the NCCAM, 
examined the effects of polyphenols from the leaves of the green tea 
plant, which are thought to fight free radicals (highly unstable 
molecules that can damage cells) and have anticarcinogenic activity. 
Compared with the control group, the mice treated with green tea 
polyphenols had reduced immunosuppression from the UV radiation. This 
same group of mice also showed more rapid repair of DNA damaged by UV 
radiation. Further, the study showed that green tea polyphenols 
increased the levels of some nucleotide excision repair genes, which 
allow for DNA repair. The researchers noted that this study is the 
first to show that preventing skin cancer with green tea polyphenols in 
water may be due to the blocking of UV-induced immunosuppression in 
mice. More studies are needed to determine if green tea has any 
potential chemopreventive effect on skin cancer in people. http://
nccam.nih.gov/research/results/spotlight/022110.htm.--Cancer Prevention 
Research. 2010;3(2):179-189.
    Cinnamon Bark and Ginseng in Herbal Formulas Increase Life Span of 
Roundworms.--Researchers used a roundworm that has some genetic and 
biochemical similarities to humans to examine complex herbal 
preparations thought to combat adverse effects of aging. The worms, 
called Caenorhabditis elegans, or C. elegans, have a brief life span 
(about 20 days). The researchers assessed two traditional Chinese 
multiherbal formulas--Huo Luo Xiao Ling Dan (HLXL), taken for chronic 
inflammatory pain (e.g., joint pain from arthritis); and Shi Quan Da Bu 
Tang (SQDB), taken to reduce fatigue and improve general wellness. They 
found that cinnamon bark, a component of both formulas, increased the 
worms' life span. Of all the individual components tested, two 
significantly prolonged life span: Cinnamomum cassia bark (present in 
both formulas) and Panax ginseng root (present in SQDB only). In light 
of these findings, the researchers concluded that C. elegans is a valid 
model for evaluating complex herbal preparations and may provide 
insight for future studies on longevity-promoting herbs. http://
nccam.nih.gov/research/results/spotlight/052510.htm.--PLoS ONE [online 
journal]. 2010;5(2):9339.
    Laboratory Study Explores Anti-HIV Potential of Palmitic Acid.--In 
a laboratory study, a fatty acid from seaweed reduced the ability of 
HIV-1 viruses to enter immune system cells. Researchers evaluated 
palmitic acid (from Sargassum fusiforme, a type of seaweed that grows 
off the coasts of Japan and China) to see if palmitic acid reduced the 
ability of HIV-1 viruses to enter CD4+ T-cells (white blood cells that 
are HIV-1's main target). Palmitic acid blocked both X4-tropic and R5-
tropic viruses, the HIV viruses that use a particular receptor (X4 or 
R5) to enter a cell. In addition, the study's findings showed that 
palmitic acid protected other cells against HIV-1, reducing X4 
infection in primary peripheral blood lymphocytes and R5 infection in 
primary macrophages (white blood cells). In all cases, the extent of 
the blocking effect depended on the concentration of palmitic acid, and 
most cells remained viable (alive) after treatment. The researchers 
noted that understanding the relationship between palmitic acid and CD4 
may lead to development of an effective microbicide product for 
preventing sexual transmission of HIV. http://nccam.nih.gov/research/
results/spotlight/121409.htm.--AIDS Research and Human Retroviruses. 
2009;25(12):1231-1241.
    Study Uses Rat Liver Cells To Explore Cholesterol-Lowering 
Mechanisms of Tea.--There is evidence that tea consumption can reduce 
the risk of cardiovascular disease, apparently by lowering cholesterol 
levels in the blood. Researchers examined extracts from both green tea 
and black tea, as well as some components of green tea, for their 
effects on the synthesis of cholesterol in liver cells from rats. The 
study's finding that black tea was more effective than green tea in 
decreasing cholesterol synthesis in rat liver cells was unexpected, as 
was the finding that EGCG alone was less effective than whole green 
tea. Additional research may reveal more about the cholesterol-lowering 
mechanisms of both kinds of tea. http://nccam.nih.gov/research/results/
spotlight/040510.htm.--Journal of Nutritional Biochemistry. 2009 
Oct;20(10):816-822.
    Evidence in Mice May Spur More Research on Fish Oil and Curcumin 
for Alzheimer's Disease.--A popular dietary supplement and a curry 
spice may affect Alzheimer's disease--related chemical processes in the 
brain, according to research findings. This study, which used an animal 
(mouse) model of Alzheimer's disease, builds on previous research 
linking the disease to peptides (amino acid chains) called b-amyloids 
and to defective insulin-processing by the brain. A particular b-
amyloid, Ab-42, is associated with Alzheimer's disease. Funded in part 
by the NCCAM, the study looked at two dietary supplements: fish oil 
rich in the omega-3 fatty acid docosahexaenoic acid (DHA); and 
curcumin, a component of turmeric. Researchers fed the Alzheimer's 
disease--model mice a regular or fatty diet; some of the mice also 
received fish oil and/or curcumin. They found that the high-fat diet 
increased Alzheimer's disease--related chemical processes in the brain, 
and that fish oil and curcumin, alone or in combination, counteracted 
this effect. DHA and curcumin also protected cognitive performance for 
mice on the high-fat diet--i.e., how well the mice remembered a maze. 
http://nccam.nih.gov/research/results/spotlight/070109.htm.--Journal of 
Neuroscience. 2009;29(28):9078-9089.
    Animal Study Shows Connection Between Vitamin E, Lung Inflammation, 
and Asthma.--Citing study results in mice, researchers reported for the 
first time that the form of vitamin E found primarily in food (gamma-
tocopherol) increased lung inflammation in induced asthma, while the 
form of vitamin E found primarily in dietary supplements (alpha-
tocopherol) reduced inflammation. The researchers found that compared 
with placebo, alpha-tocopherol significantly reduced inflammation while 
gamma-tocopherol significantly increased inflammation. The researchers 
also found that the mechanism by which both forms of vitamin E work 
involves the regulation of endothelial cell signals during leukocyte 
(white blood cell) recruitment--a process that occurs during 
inflammation. Endothelial cells line the inner walls of blood vessels. 
The researchers concluded that the opposing activities of the two 
common forms of vitamin E on inflammation found in this study are 
consistent with the contradictory outcomes of vitamin E on asthma in 
previous clinical trials. They also noted that the information gained 
from this study could have a significant impact on designing and 
interpreting future clinical studies on vitamin E. http://
nccam.nih.gov/research/results/spotlight/041109.htm.--The Journal of 
Immunology. 2009;182(7):4395-4405.
    Researchers Investigate Anti-inflammatory Effects of Pineapple 
Extract.--Previous research indicates that bromelain--an enzyme 
extracted from pineapple stems--may help inflammatory conditions such 
as allergic airway disease. Bromelain's anti-inflammatory effects have 
been attributed to its ability to alter the activation and expansion of 
the immune system's CD4+ T cells (a type of lymphocyte). To better 
understand the processes involved, the NCCAM-funded researchers 
conducted in vitro experiments with mouse cells, using bromelain 
derived from a commercially available, quality-tested product. The 
results show that bromelain reduces CD25 (a protein involved in 
inflammation) expression via proteolytic (enzymatic) action, in a dose- 
and time-dependent manner. The researchers' analysis of the mechanism 
involved found that bromelain apparently splits CD25 from the CD4+ T 
cells, and that the T cells remain functional--i.e., they can still 
divide--after bromelain treatment. The researchers concluded that the 
novel mechanism of action demonstrated in their experiment explains how 
bromelain may exert its therapeutic benefits in inflammatory 
conditions. http://nccam.nih.gov/research/results/spotlight/
080309.htm.--International Immunopharmacology. 2009;9(3):340-346.
    Grape Seed Extract May Help Neurodegenerative Diseases.--In light 
of previous studies indicating that grape-derived polyphenols may 
inhibit protein misfolding, researchers examined the potential role of 
a particular grape seed polyphenol extract (GSPE) in preventing and 
treating tau-associated neurodegenerative disorders. The results of 
their in vitro study showed that GSPE is capable of interfering with 
the generation of tau protein aggregates and also disassociating 
preformed aggregates, suggesting that GSPE may affect processes 
critical to the onset and progression of neurodegeneration and 
cognitive dysfunctions in tauopathies. The researchers concluded that 
their laboratory findings, together with indications that this GSPE is 
likely to be safe and well-tolerated in people, support its development 
and testing as a therapy for Alzheimer's disease. http://nccam.nih.gov/
research/results/spotlight/031209.htm.--Journal of Alzheimer's Disease. 
2009;16(2):433-439.
    Chinese Herbal Formula Shows Anti-Arthritis Effects in Animal 
Study.--Researchers analyzed the effects of a modified version of the 
classic Chinese formula Huo Luo Xiao Ling Dan (HLXL) in an animal (rat) 
model of adjuvant arthritis, which shares some features with human 
rheumatoid arthritis. The researchers induced adjuvant arthritis in 
male rats by injecting them with a complete Freund's adjuvant solution 
containing heat-killed Mycobacterium tuberculosis. On days 16 to 25, 
the rats were given a daily oral dose of either a quality controlled, 
11-herb HLXL preparation or liquid only. Compared with controls, the 
HLXL-treated rats had significantly decreased arthritis symptom scores; 
reduced paw edema; and lower TNF-a and IL-1b levels. No adverse effects 
were observed. Based on their results, the researchers concluded that 
this HLXL formula may have benefits for treating arthritis and related 
inflammatory disorders. http://nccam.nih.gov/research/results/
spotlight/071609.htm.--Journal of Ethnopharmacology. 2009;121(3):366-
371.
    Echium Oil Reduces Triglyceride Levels in Mice.--In light of 
previous research indicating that oil from the seeds of the Echium 
plantagineum plant can lower triglycerides in people, researchers used 
an animal model--mice with mildly elevated triglyceride levels--to 
investigate how echium oil achieves this effect. The researchers fed 
the mice diets supplemented with either echium oil, fish oil, or (as a 
control) palm oil. They found that both echium and fish oils had the 
following effects: reduced triglycerides in blood plasma and the liver; 
enriched EPA in plasma and the liver--echium less so than fish oil; and 
``down-regulated'' (decreased the expression of) several genes involved 
in synthesis of triglycerides in the liver. The researchers concluded 
that echium oil may provide a botanical alternative to fish oil for 
reducing triglycerides. http://nccam.nih.gov/research/results/
spotlight/022509.htm.--Journal of Nutritional Biochemistry. 
2008;19(10):655-663.
    Laboratory Study Shows Black Cohosh Promotes Bone Formation in 
Mouse Cells.--Results of laboratory research are the first to indicate 
that extracts of the herb black cohosh (Actaea racemosa) may stimulate 
bone formation. Researchers added an extract of black cohosh to a 
culture of bone-forming mouse cells. The researchers observed that a 
high dose (1,000 ng/mL) of the extract suppressed the production of 
these bone-forming cells, yet a lower dose (500 ng/mL) significantly 
increased the formation of bone nodules. When the cells were treated 
with a protein whose molecules attach to estrogen receptors in place of 
estrogen, this effect on bone nodule formation disappeared. Thus, the 
researchers suggest that ingredients within black cohosh contain a 
component that acts through estrogen receptors. The researchers 
concluded that their results provide a scientific explanation at the 
molecular level for claims that black cohosh may protect against 
postmenopausal osteoporosis. They also noted that studying extraction 
methods and identifying black cohosh's active components may make it 
possible to develop new ways to prevent and treat this condition. 
Although results from the study suggest that black cohosh may have 
potential implications for the prevention or treatment of 
postmenopausal bone loss, there is no evidence yet that this laboratory 
research can be extended to treatments in people. http://nccam.nih.gov/
research/results/spotlight/090408.htm.--Bone. 2008;43(3):567-573.
    Pomegranate Extract May Be Helpful for Rheumatoid Arthritis (RA).--
RA is an autoimmune disease characterized by joint pain, stiffness, 
inflammation, swelling, and sometimes joint destruction. The 
pomegranate has been used for centuries to treat inflammatory diseases, 
and people with RA sometimes take dietary supplements containing a 
pomegranate extract called POMx. However, little is known about the 
efficacy of POMx in suppressing joint problems associated with RA. 
Researchers used an animal model of RA--collagen-induced arthritis 
(CIA) in mice--to evaluate the effects of POMx. They found that POMx 
significantly reduced the incidence and severity of CIA in the mice. 
The arthritic joints of the POMx-fed mice had less inflammation, and 
destruction of bone and cartilage were alleviated. Consumption of POMx, 
the researchers also concluded, selectively inhibited signal 
transduction pathways and cytokines critical to development and 
maintenance of inflammation in RA. Although previous studies of POMx 
found cartilage-protective effects in human cell cultures, this is the 
first study to observe positive effects in a live model. The 
researchers note that the data from this study suggest the potential 
efficacy of POMx for arthritis prevention, but not for treatment in the 
presence of active inflammation; future studies will address disease-
modifying effects of POMx. They also note that clinical trials are 
needed before POMx can be recommended as safe and effective for RA-
related use in people. http://nccam.nih.gov/research/results/spotlight/
120508.htm.--Nutrition. 2008;24(7--8):733-743.
    Two Studies Explore the Potential Health Benefits of Probiotics.--
In two studies, researchers investigated how probiotics may have a role 
in treating gastrointestinal illnesses, boosting immunity, and 
preventing or slowing the development of certain types of cancer. In 
one study, researchers investigated how Lactobacillus reuteri ATCC PTA 
6475 might work to slow the growth of certain cancerous tumors. Their 
study documented the molecular mechanisms of the probiotic's effects in 
human myeloid leukemia-derived cells--i.e., how it regulates the 
proliferation of cancer cells and promotes cancer cell death. The 
researchers noted that a better understanding of these effects may lead 
to development of probiotic-based regimens for preventing colorectal 
cancer and inflammatory bowel disease. In another study, researchers 
looked at whether Lactobacillus acidophilus might enhance the immune-
potentiating effects of an attenuated vaccine (a vaccine prepared from 
a weakened live virus) against human rotavirus infection--the most 
common cause of severe dehydrating diarrhea in infants and children 
worldwide. The investigators' tests on newborn pigs found that animals 
given both a vaccine and the probiotic had a better immune response 
than the animals given the vaccine alone. The researchers concluded 
that probiotics may offer a safe way to increase the effectiveness of 
rotavirus vaccine in humans. In both studies, the investigators called 
for additional research into the mechanisms behind the health-related 
effects of probiotics. http://nccam.nih.gov/research/results/spotlight/
110508.htm.--Cellular Microbiology. 2008;10(7):1442-1452.--Vaccine. 
2008;26(29--30):3655-3661.
    Research Shows Promise of Pineapple Extract for Inflammatory Bowel 
Disease (IBD).--IBD, including Crohn's Disease (CD) and ulcerative 
colitis (UC), are characterized by inflammation of the gastrointestinal 
tract. Researchers have found that bromelain--an enzyme derived from 
pineapple stems--might be able to reduce inflammation in IBD. 
Researchers recruited patients with a confirmed diagnosis of CD or UC 
as well as a normal, non-IBD control group. In total, this pilot study 
recruited 51 participants: 8 controls, 20 with UC, and 23 with CD. To 
assess the effect of a bromelain preparation on the production of 
cytokines, colon biopsies obtained from patients with UC, CD, and 
normal controls were treated in the lab (in vitro) with bromelain. The 
researchers report that bromelain reduced production of several pro-
inflammatory cytokines and chemokines that are elevated in IBD and play 
a role in the progression of IBD. The authors conclude that bromelain 
treatment could potentially benefit IBD patients if similar changes 
also occur when colon tissues are exposed to bromelain inside the body. 
The researchers also suggest that additional research is needed to 
understand how bromelain influences chemokine and cytokine production. 
http://nccam.nih.gov/research/results/spotlight/070108.htm.--Clinical 
Immunology (2008) 126, 345-352.
    Grape Seed Extract May Help Prevent and Treat Alzheimer's.--
Emerging research shows a correlation between red wine consumption and 
reduced risk of Alzheimer's disease-type cognitive decline. Researchers 
found that grape seed-derived polyphenolics--similar to that in red 
wine--significantly reduced Alzheimer's disease-type cognitive 
deterioration in mice. Researchers conducted experiments in mice with 
Alzheimer's disease to see if a highly purified polyphenolic extract 
from Vitis vinifera (cabernet sauvignon) grape seeds, could affect 
Alzheimer's disease-type cognitive deterioration. The mice received 5 
months of either water containing grape seed extract or water alone as 
a placebo treatment. The mice were then given behavioral maze tests to 
determine cognitive function and brain tissue samples were tested to 
determine evidence of disease. The researchers found that mice treated 
with grape seed extract had significantly reduced Alzheimer's disease-
type cognitive deterioration compared to the control mice. This is due 
to the prevention of a molecule called amyloid forming in the brain 
that has been shown to cause Alzheimer's disease-type cognitive 
impairment. http://nccam.nih.gov/research/results/spotlight/
062408.htm.--The Journal of Neuroscience. 2008. 28(25);6388-6392.
    Chinese Herbal Formula May Be Helpful for Peanut Allergies.--A 
study in mice shows that a Chinese herbal formula may help prevent 
dangerous reactions to peanuts. Peanut allergies affect as many as 6 
percent of young children and are a major cause of anaphylaxis--a 
severe allergic reaction with respiratory symptoms that can be fatal. 
Researchers conducted experiments in mice with established peanut 
allergies to see if a formula of nine Chinese herbs, called FAHF-2, 
could reduce sensitivity to peanuts. The peanut-sensitive mice received 
7 weeks of oral treatment with FAHF-2 or water as a placebo treatment. 
The mice were then exposed to peanuts at 2 different times to see if 
they would have anaphylactic reactions. The researchers found that 
FAHF-2 completely protected the mice from a dangerous reaction on both 
occasions--showing that protection lasted at least 4 weeks after the 
treatment finished. The mice treated with the placebo (water) had 
anaphylactic reactions. The researchers note that the protection of 
FAHF-2 may result from a shift in the immune balance away from the 
allergic response. http://nccam.nih.gov/research/results/spotlight/
012908.htm.--Clinical and Experimental Allergy, June 2007.
    Turmeric and Rheumatoid Arthritis Symptoms.--More than 2 million 
Americans suffer from rheumatoid arthritis (RA), a condition in which 
the body's immune system attacks the joints, causing pain, swelling, 
stiffness, and loss of function. The herb turmeric has been used for 
centuries in Ayurvedic medicine (a whole medical system that originated 
in India) as a treatment for inflammatory disorders, including RA. To 
study the effects of turmeric, researchers created symptoms in rats 
that mimic those of RA in humans. In a series of experiments, they 
treated the rats with different preparations and dosages of turmeric 
extracts. The results, measured in terms of joint swelling, suggested 
that an extract containing only curcuminoids (a family of chemicals 
that is the major component of turmeric) may be more effective for 
preventing RA symptoms than a more complex extract containing 
curcuminoids plus other turmeric compounds. They also noted that the 
curcuminoids-only formulas appeared safer and more effective at lower 
doses. Also, the researchers found that the compounds had greater 
effectiveness when the rats were treated before instead of after the 
onset of inflammation. The authors identified a need for well-designed 
preclinical and clinical studies to look further into turmeric for 
anti-inflammatory use. http://nccam.nih.gov/research/results/spotlight/
030106.htm.--Journal of Natural Products, March 2006.

            Other Research

    Botanicals May Help Conditions Associated With Aging.--To evaluate 
the effectiveness of botanicals in relation to conditions such as high 
blood pressure, cardiovascular disease, cognitive decline, insulin 
resistance, and excess fats in the blood, researchers conducted a 
literature review and examined studies from their own laboratory. The 
researchers looked at effects of dietary soy; soy isoflavones (daidzein 
and genistein); grape seed extract, which has a high concentration of 
polyphenols; and puerarin, an isoflavone found in kudzu. The literature 
review found that soy seemed to lower blood pressure in men and 
postmenopausal women, help protect against cardiovascular diseases 
(including heart disease and atherosclerosis), and benefit people with 
diabetes. The researchers' own animal studies found that soy 
isoflavones protected against salt-sensitive hypertension in male rats 
and in female rats whose ovaries had been removed (OVX); grape seed 
extract reduced blood pressure and improved cognitive functioning in 
OVX female rats; and puerarin improved glucose control in male mice. 
The researchers concluded that the botanical compounds reviewed appear 
to have beneficial effects in animal models of disease (soy also has 
shown benefits in humans), and that the compounds may be more effective 
in relation to cardiovascular, metabolic, and cognitive function than 
for menopausal symptoms. They recommended that the compounds' safety 
and mechanisms of action should be carefully tested in the context of 
the disease status of potential users. http://nccam.nih.gov/research/
results/spotlight/121008.htm.--Gender Medicine. 2008;
5(suppl A):76S-90S.
    Botanical Research Centers Featured in American Journal of Clinical 
Nutrition.--The February 2008 issue of the American Journal of Clinical 
Nutrition features eight articles from the NIH Botanical Research 
Centers Program, which is co-funded by the NIH Office of Dietary 
Supplements and the NCCAM. The articles highlight different areas 
related to the Centers' research into botanical use, safety, and 
efficacy. They include evaluation of botanicals for improving health; 
technologies and experimental approaches to evaluating botanicals; 
botanicals and metabolic syndrome; echinacea in infection; botanicals 
for age-related diseases; ways in which botanical lipids affect 
inflammatory disorders; botanicals to improve women's health; and 
ensuring botanical dietary supplement safety. The Botanical Centers are 
intended to advance research activities in plant identification, as 
well as preclinical research and early phase clinical studies. Each 
Center has a broad interdisciplinary research program that focuses on 
collaborative activities. Each of the Centers was created with a high 
potential for translating findings into public health benefits. http://
nccam.nih.gov/research/results/spotlight/042308.htm.--American Journal 
of Clinical Nutrition, 2008. Volume 87, Number 2, 463.

Population-based Research

            Cancer Survivors Are More Likely Than General Population To 
                    Use CAM, According to National Survey Analysis
    A recent analysis of the 2007 National Health Interview Survey 
revealed that cancer survivors are more likely to use complementary and 
alternative medicine (CAM) compared with the general population. Cancer 
survivors are also more likely to use CAM based on a recommendation by 
their healthcare providers and to talk to their healthcare providers 
about their CAM use. Although cancer survivors communicated more about 
their CAM use than the general population, the study authors emphasized 
the overall need for improving communication between patients and 
providers about CAM use to help ensure coordinated care. http://
nccam.nih.gov/research/results/spotlight/032011.htm.--Journal of Cancer 
Survivorship: Research and Practice. 2011;5(1):8-17.

            Analysis of National Survey Shows CAM Use in People With 
                    Pain or Neurological Conditions
    According to an analysis of the 2007 National Health Interview 
Survey, approximately 44 percent of American adults with pain or 
neurological conditions, compared to about 33 percent of people without 
those conditions, used complementary and alternative medicine (CAM) 
during the previous year. The most common CAM therapies used by people 
with these conditions were mind-body therapies (25 percent), such as 
deep breathing exercises, meditation, and yoga; biologically based 
therapies (21 percent), such as herbal therapies; manipulative and 
body-based therapies (19 percent), such as massage and chiropractic 
care; and alternative medical systems (4 percent). In addition, 
respondents with pain or neurological conditions indicated that they 
used CAM because conventional treatment did not work (20 percent vs. 10 
percent) and was too expensive (9 percent vs. 4 percent). The 
researchers noted that this analysis demonstrates the need for more 
robust studies on the efficacy of CAM therapies for people with these 
conditions. http://nccam.nih.gov/research/results/spotlight/
111010.htm.--Journal of Neurology. 2010;257:1822-1831.

            Study Asks Adolescents With Inflammatory Bowel Disease 
                    About Use of Complementary and Alternative Medicine 
                    (CAM) Mind-body Therapies
    This study found that many adolescents with inflammatory bowel 
disease are currently using or would consider using CAM--specifically 
mind-body therapies such as relaxation and guided imagery--to help 
manage their symptoms. This disease is actually a group of disorders 
(including Crohn's disease and ulcerative colitis) that cause 
inflammation of the intestines. The physical and emotional problems 
associated with irritable bowel disease in adolescents often affect 
quality of life. The researchers noted that their findings provide 
groundwork for future studies to determine the effect of CAM therapies 
on health outcomes in adolescents with inflammatory bowel disease. 
http://nccam.nih.gov/research/results/spotlight/031110.htm.--
Inflammatory Bowel Disease. 2010;16(3):501-506.

            Certain Categories of Complementary Therapies Appear To 
                    Benefit Older Adults
    According to a recent analysis of data from the 2002 National 
Health Interview Survey and the 2003 Medical Expenditure Panel Survey, 
use of biologically based therapies (e.g., herbs or megavitamins) and 
manipulative/body-based therapies (e.g., chiropractic or massage) may 
be associated with better health outcomes among individuals age 55 
years and older. The analysis showed a statistical association between 
ability to function and use of biologically based therapies and 
manipulative/body-based therapies. The researchers concluded that some 
categories of complementary therapies may be more beneficial than 
others for older adults. They cautioned that these findings should not 
be interpreted as evidence for the efficacy of specific therapies. 
Although the findings indicate that the use of certain kinds of CAM 
therapies is associated with better health outcomes for older adults, 
only clinical trials can determine the efficacy of specific therapies. 
The researchers also noted that this is the first longitudinal 
assessment (analysis of data collected from the same people at 
different points in time) of possible connections between complementary 
therapy use and health outcomes in a national sample of older adults. 
They recommended additional population-based research in this area. 
http://nccam.nih.gov/research/results/spotlight/070810.htm.--Journal of 
Alternative and Complementary Medicine. 2010;16(7):701-706.

            Many Older People Use Both Prescription Drugs and Dietary 
                    Supplements
    Researchers analyzed the use of prescription drugs and dietary 
supplements in a sample of 3,070 people aged 75 and older. The data had 
been gathered during the Gingko for the Evaluation of Memory (GEM) 
study, a clinical trial that examined the effects of Gingko biloba on 
the development of dementia. Nearly 75 percent of the GEM study 
participants took at least one prescription drug and one dietary 
supplement. Approximately 33 percent used three or more prescription 
drugs and three or more supplements. Furthermore, 10 percent of the 
participants combined five or more prescription drugs with five or more 
dietary supplements. Although supplements were taken along with all 
types of prescription drugs, individuals using prescribed nonsteroidal 
anti-inflammatory drugs (NSAIDs), thyroid drugs, and estrogens were 
more likely to use dietary supplements. Individuals who used 
prescription drugs for high blood pressure and diabetes were less 
likely to use dietary supplements. Based on these data, they recommend 
that patients discuss dietary supplement use with their healthcare 
providers. In addition, the researchers emphasized the need for further 
investigations to better define the clinical importance of interactions 
between drugs and supplements. http://nccam.nih.gov/research/results/
spotlight/071509.htm.--Journal of the American Geriatric Society. 
2009;57(7):1197-1205.

            Translating CAM Research Results Into Clinical Practice: 
                    Results From a National Survey of Physicians and 
                    CAM Providers
    In an initial investigation of the potential for information from 
CAM research to influence clinical practice, a 2007 national survey 
asked acupuncturists, naturopaths, internists, and rheumatologists 
about their awareness of CAM clinical trials, their ability to 
interpret research results, and their use of research evidence in 
decisionmaking. The survey focused on awareness of two major NCCAM-
funded clinical trials that studied acupuncture or glucosamine/
chondroitin for osteoarthritis of the knee. Fifty-nine percent of the 
1,561 respondents were aware of at least one of the two clinical trials 
but only 23 percent were aware of both trials. The acupuncture trial 
was most familiar to acupuncturists and rheumatologists, the 
glucosamine/chondroitin trial to internists and rheumatologists. 
Overall, awareness was greatest among rheumatologists and those 
practicing in institutional or academic settings. All groups regarded 
clinical experience as ``very important'' in their decisionmaking, 
although CAM providers were more likely to rate it ``most important.'' 
Physicians were much more likely than CAM providers to consider 
research results very important or ``very useful'' in their clinical 
decisionmaking. The survey team concluded that CAM research has the 
potential to make a difference in both conventional and alternative 
medicine clinical practice. They recommend concerted efforts to better 
train all clinicians in interpretation and use of evidence from 
research studies, and to improve the dissemination of research results. 
http://nccam.nih.gov/research/results/spotlight/041309.htm.--Archives 
of Internal Medicine. 2009;169(7): 670-677.

            National Survey Reports on CAM Use by Adults and Children
    The 2007 The National Health Interview Survey (NHIS) found that 
approximately 38 percent of adults and 12 percent of children use some 
form of CAM. Among both adults and children, the most commonly used CAM 
therapy is nonvitamin/nonmineral natural products; fish oil/omega-3 is 
the most popular natural product for adults, while echinacea is the 
most popular for children. Back pain is by far the most common 
condition prompting adults to use CAM. Among children, back or neck 
pain is the most common reason for using CAM, followed closely by head/
chest colds. The 2002 NHIS also included a supplement on CAM use by 
adults. Overall usage among adults in 2002 (36 percent) was about the 
same as in 2007. Since 2002, usage has increased for some therapies, 
including deep breathing, meditation, massage, and yoga. Adult use of 
CAM for head/chest colds showed a marked decrease between 2002 and 
2007. The 2007 survey was the first to ask about CAM use by children. 
http://nccam.nih.gov/research/results/spotlight/123108.htm.--CDC 
National Health Statistics Report #12. 2008.

            New Findings on Sleep Disorders and CAM
    Based on a national survey, the NCCAM scientists found that over 
1.6 million American adults use some form of CAM to treat insomnia or 
trouble sleeping. The authors key findings are:
  --More than 17 percent of adults reported insomnia or trouble 
        sleeping in the past 12 months. In this group, 4.5 percent used 
        some form of CAM to treat these problems.
  --The CAM users were most likely to use biologically based therapies 
        (nearly 65 percent), such as herbal therapies, or mind-body 
        therapies (more than 39 percent), such as relaxation 
        techniques. Most who used these two types of therapies said 
        they were at least somewhat helpful for insomnia or trouble 
        sleeping.
http://nccam.nih.gov/research/results/spotlight/090106.htm.--Archives 
of Internal Medicine, September 2006.

            CAM Use High Among Adolescents
    Researchers conducting the first national survey of CAM use among 
adolescents in the United States analyzed responses from 1,280 
adolescents aged 14 to 19. They found that 79 percent had used at least 
one form of CAM during their lifetime and that females used CAM more 
than males. Among all participants, almost 30 percent had used one or 
more dietary supplements, and almost 10 percent had used supplements 
along with prescription medications in the preceding month. Many of the 
supplements the teens reported using were related to attempts to change 
body shape (e.g., creatine and weight-loss products). The authors urged 
that healthcare providers be aware of CAM and dietary supplement use by 
their adolescent patients, because of the lack of standardization in 
supplements, as well as their potential for safety risks and 
interactions with prescription medications.http://nccam.nih.gov/
research/results/spotlight/040106.htm.--Journal of Adolescent Health 
April 2006.

            More Than One-third of U.S. Adults Use Complementary and 
                    Alternative Medicine, According to a 2002 
                    Government Survey
    According to the 2002 National Health Interview Survey (NHIS), 36 
percent of U.S. adults use some form of CAM. The most commonly used 
form of CAM was natural products (such as herbs and other botanicals). 
Other popular CAM therapies included deep breathing, meditation, 
chiropractic care, yoga, massage, and special diets. Echinacea was the 
most commonly used natural product. CAM was most often used to treat 
back pain, colds, neck pain, joint pain, and anxiety or depression. The 
survey also revealed variations in CAM use by population subgroups. For 
example, CAM use overall was more common among women, people with 
higher education, people who had been hospitalized in the past year, 
and former smokers (compared to current smokers or those who had never 
smoked). The authors noted that the information from this survey is a 
foundation for future studies of CAM as it relates to health and 
disease among population subgroups. http://nccam.nih.gov/research/
results/spotlight/050810.htm.--CDC Advance Data Report #343. 2004.

                     THE NCCAM RESEARCH APPROACHES

    Question. Individualized therapies that involve multiple approaches 
often do not lend themselves to traditional double-blind studies but 
are frequently used in integrative medicine. Please describe work that 
the NCCAM is doing to support research on these kinds of treatments.
    Answer. The NCCAM recognizes that assessing some of the 
individualized therapies used in integrative medicine in double-blind 
studies is challenging. Similar challenges confront other disciplines 
of healthcare research that employ individualized or multifaceted 
interventions, complex procedures, or system approaches (e.g. 
cognitive-behavioral therapy, surgery, or behavior change strategies). 
There is broad interest within the biomedical and behavioral research 
communities in applying effectiveness and outcomes approaches and 
pragmatic trial designs to such questions.
    Addressing this challenge is a high priority for the NCCAM as 
evidenced by its inclusion as one of our strategic plan objectives: to 
``develop research examining the contributions of specific promising 
CAM approaches to better treatment and health promotion using the real-
world methods and tools of the disciplines of observational, outcomes, 
health services, and effectiveness research.'' These methods and 
approaches also offer potential to address the challenges of conducting 
CAM research that reflects practice in the real world.
    Health provider networks, practice-based clinical research 
networks, and integrative medicine practices provide important venues 
in which to develop real-world evidence across a broad array of outcome 
measures regarding the effects and effectiveness of CAM approaches and 
their integration into strategies for treatment and health promotion. 
Practice-based research provides an important setting in which to study 
the complex interplay of intervention, the patient-provider 
relationship, and other important contextual and environmental factors 
involved in healthcare and health promotion. Indeed, many CAM and 
integrative care practices actively seek to employ these factors. 
Population-based and practice-based research strategies also offer 
great potential for developing evidence regarding the effectiveness of 
CAM-related interventions in engaging individuals in health-promoting 
behaviors and practices.
    The NCCAM is pursuing these approaches in the context of CAM and 
integrative medicine practice through collaboration with experts who 
confront similar challenges and opportunities. For example, the NCCAM 
is working with our colleagues at the Departments of Defense and 
Veterans Affairs to explore ways that CAM mind and body approaches can 
be used in integrative approaches to treat pain, stress disorders, and 
other symptoms. Further, the NCCAM has released a funding opportunity 
announcement to foster development of CAM research methodology titled, 
``Translational Tools for Clinical Studies of Mind/Body and Manual 
Therapy CAM Interventions.'' It will ``encourage the development of 
improved research methodology to study safety, efficacy, and clinical 
effectiveness of mind-body interventions.''
    Additionally, the NCCAM has substantially increased its investment 
in research which advances our understanding of the usefulness of CAM 
interventions in real world settings. For example, in one promising 
study being funded by the NCCAM at the Mount Sinai School of Medicine, 
researchers are studying methods to utilize all available information 
regarding CAM treatments in patients with HIV. By utilizing randomized 
controlled trials along with observational studies, expert judgment and 
other types of data, they seek to develop a clinical prediction model 
to determine which CAM interventions are beneficial. Another study, 
this one at Brigham and Women's Hospital, is looking at the 
effectiveness of an integrative healthcare team at improving outcomes 
for chronic low back pain by focusing on observational data. These are 
just two examples of studies funded by the NCCAM that go beyond 
traditional double-blind studies by using real world data to support 
CAM research.

   NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS) AND 
                         PREVENTATIVE MEDICINE

    Question. One goal of the NCATS is to accelerate the process by 
which scientific discoveries are turned into treatments and cures--
moving discoveries more quickly through the ``valley of death'' or the 
time between discovery and available cures. In particular, the NIH has 
indicated that the NCATS would focus on the drug development pipeline 
with a hope of understanding and addressing the reasons that so many 
drugs fail in development. Meanwhile, research has increasingly shown 
how a healthy lifestyle, exercise or better nutrition can help prevent 
the onset of disease or the use of expensive medicines or treatments. 
Will translational research that focuses on prevention or disease 
control through lifestyle changes be incorporated into the new vision 
for the NCATS? If so, how? Or will the NCATS focus exclusively on drug 
development?
    Answer. As you point out, the prevention of diseases as well as 
their successful treatment may often require behavioral and lifestyle 
interventions or strategies. As such, a clear understanding of, and 
further research into, the role of behavioral and lifestyle factors in 
human health will be critical to the NCATS' success in catalyzing the 
development of new strategies to address human health and disease. The 
NCATS will support research to generate new methods and approaches 
aimed at accelerating the development, testing, and implementation of 
diagnostics, therapeutics, and prevention strategies. The NCATS 
prevention and behavioral research will be coordinated with the related 
work of the other NIH Institutes and Centers as well as with the Office 
of Disease Prevention and the Office of Behavioral and Social Sciences 
Research and carried out in part through the 60 institutions with 
Clinical and Translational Science Awards.

             BUDGETARY CONSTRAINTS ON UNIVERSAL FLU VACCINE

    Question. The NIH-supported scientists are making significant 
progress toward developing a universal flu vaccine that would confer 
longer term protection against multiple influenza virus strains and 
make yearly flu shots a thing of the past. What would be the impact on 
public health if research on the universal flu vaccine were delayed or 
scaled back due to budget constraints at the NIH?
    Answer. The costly and time-consuming annual process of 
manufacturing, distributing, and administering millions of doses of 
seasonal influenza vaccine would become obsolete if researchers could 
design a vaccine that provides protection against a broad range of 
influenza strains over multiple influenza seasons. One strategy to 
overcome the need for a yearly influenza vaccine is to develop a 
vaccine against the common components of the influenza virus that do 
not change from year to year or from strain to strain. Recently, 
researchers supported by the National Institute of Allergy and 
Infectious Diseases (NIAID) have made significant breakthroughs in 
identifying the specific parts of influenza viral proteins that are 
unchanged among both seasonal and pandemic strains. So-called 
``universal'' influenza vaccines that capitalize on these findings 
might one day provide protection against the broad range of viruses 
arising from seasonal antigenic drift (minor changes) and pandemic 
antigenic shift (major changes) that are the hallmark of influenza 
viruses.
    The NIAID is supporting a number of research projects to develop a 
vaccine that induces a potent immune response to the common elements of 
the influenza A virus that undergo very few changes from season to 
season and from strain to strain. Conserved internal proteins of the 
virus such as the M2 protein and conserved regions of the influenza 
envelope protein hemagglutinin (HA) have been identified as promising 
vaccine targets. For example, the NIAID-supported researchers found 
that a vaccine based on the M2 protein of H5N1 avian influenza virus 
elicited strong immune responses in mice. The HA protein of influenza 
virus, which is the protective antigen of the virus, has both a 
``head'' region and a ``stem'' region. The NIAID-funded researchers 
recently generated a novel form of HA that elicited broadly cross-
reactive antibodies against the stem region of a number of divergent 
seasonal and pandemic influenza subtypes and provided protection 
against disease in mouse challenge studies. In addition, the NIAID 
intramural researchers in the Vaccine Research Center demonstrated that 
a ``prime-boost'' vaccine strategy based on conserved regions of the HA 
protein could protect animals from infection with multiple strains of 
influenza that had been prevalent over many years. This ``prime-boost'' 
vaccine strategy involves first priming the immune system with a 
vaccine containing the DNA of an influenza surface protein (HA) and 
then administering a second vaccine made from a seasonal influenza 
virus or from a weakened cold virus, to amplify the immune response 
generated by the first vaccine.
    Budget reductions could adversely affect the NIAID's ability to 
continue support of these activities in a robust and timely manner. 
Funding cuts could delay the development of new candidate vaccines for 
universal influenza and improved vaccines for seasonal influenza, as 
well as delay initiation of clinical trials necessary to test these 
vaccines. However, if budget reductions do materialize, the NIH would 
have to reevaluate its research priorities, and thus, the specific 
research areas to be impacted by such reductions would be determined at 
that time.

               BUDGETARY CONSTRAINTS ON VACCINE RESEARCH

    Question. What other types of vaccine research underway at the NIH 
might also have to be delayed or scaled back due to budget constraints?
    Answer. Vaccines provide a safe, cost-effective, and efficient 
means of preventing illness, disability, and death from infectious 
diseases. The NIH is recognized as a worldwide leader in basic 
immunology research that underpins all vaccine development, and 
conducts or supports preclinical and clinical research on a broad 
spectrum of new and improved vaccine candidates. Recent progress in 
global vaccine research--from the RV 144 trial in Thailand that 
demonstrated that an HIV vaccine regimen provided a modest preventive 
effect, to the NIH-sponsored research advances that may unlock 
neutralizing antibody targets for a range of infectious diseases--
highlights the need for a robust vaccine research portfolio at the NIH 
to pursue these and other advances in the field. A reduction in vaccine 
research funding at the NIH could slow the pace of ongoing efforts to 
develop new tools to prevent infectious diseases and could erode our 
ability to capitalize on scientific progress toward the development of 
vaccines.
    HIV vaccine research activities that could be slowed by reduced 
funding levels include the conduct of additional and important Phase 
IIb trials that are planned to further assess and improve upon the 
results of the RV144 HIV vaccine trial, especially in other risk groups 
and in countries other than Thailand. Reduced funding could also 
undermine other important HIV vaccine trials. For example, 
investigators conducting the HIV Vaccine Trials Network (HVTN) 505 
trial would likely be unable to expand the study to include 2,200 
participants at 21 sites in 18 U.S. cities in order to assess whether 
the candidate vaccine regimen can prevent HIV infection and/or reduce 
viral load. Decreased funding could also limit the NIH's ability to 
support efforts to identify other promising HIV vaccine candidates, and 
curtail our ability to test those candidates that hold the most promise 
and advance them into clinical trials. Again, however, specific 
research areas that may be impacted by budget reductions are subject to 
priority assessments and cannot be precisely predetermined.
    In addition to research to develop an HIV vaccine, the NIH is also 
supporting vaccine research across a range of other globally important 
diseases, including dengue, pandemic influenza, malaria, and 
tuberculosis, as well as diseases that might occur as a result of acts 
of bioterrorism. A reduction in funding could force the NIH to scale 
back efforts across many of its infectious disease research programs. 
Potential adverse effects include a reduced ability to support 
preclinical product development, which is intended to assist companies 
and academic investigators in developing essential products to prevent 
and treat infectious diseases. Reduced funding levels could limit the 
development of new and improved preclinical products required to 
confront and keep pace with emerging and re-emerging infectious 
diseases, including a planned array of vaccine-related product 
development services. Funding constraints could also adversely affect 
clinical research efforts at the NIH, limiting our ability to support 
clinical trials designed to assess influenza and malaria vaccines, and 
slowing the progress of trials. Finally, budget constraints could 
result in significant delays in advancing research projects focused on 
the development of next-generation vaccines for biodefense purposes.

                    GUIDANCE FOR USE OF CLASS B CATS

    Question. On March 18, the NIH released guidance on its plan to 
transition from the use of USDA Class B dogs to other legal sources 
(Notice NOT-OD-11-055). Why is there no mention of cats? The transition 
plan, as the NIH notes, is in accordance with the National Academy of 
Sciences report, Scientific and Humane Issues in the Use of Random 
Source Dogs and Cats in Research. The NIH notice also quotes from 
Senate report language regarding research on both dogs and cats, but 
the mention of cats was excised from the quotation. Does the NIH plan 
to issue a separate guidance dealing with cats?
    Answer. The NIH believes that sufficient numbers of cats currently 
are available through Class A vendors to support the needs of the NIH-
supported research. Therefore, no plan for phase out is needed nor a 
plan for developing sufficient animals from Class A vendors. At 
present, the NIH has no plans to issue separate guidance dealing with 
cats.

                             LUPUS RESEARCH

    Question. How are the different NIH Institutes NIAID, National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), 
National Heart, Lung, and Blood Institute (NHLBI), National Institute 
of Diabetes and Digestive and Kidney Diseases (NIDDK), General 
Medicine, among others) working together to increase support for 
research on lupus? How will the new Translational Center work to 
address diseases like Lupus that cross multiple Institutes?
    Answer. Lupus is an autoimmune disease that affects the lives of 
many Americans. Ninety percent of Americans with lupus are women. Lupus 
can affect many parts of the body, including the joints, skin, kidneys, 
heart, lungs, blood vessels, and brain. Although people with the 
disease may have different symptoms, some of the most common ones 
include extreme fatigue, painful or swollen joints (arthritis), 
unexplained fever, skin rashes, and kidney problems.
    A wide range of basic, translational, and clinical research on 
lupus is being supported by many of the Institutes, Centers, and 
Offices at the NIH. Highlights of collaborative efforts include:
  --The Lupus Federal Working Group, established on behalf of the 
        Department of Health and Human Services (HHS) Secretary by the 
        NIH, facilitates collaboration among the NIH components, other 
        Federal agencies, voluntary and professional organizations, and 
        industry groups with an interest in lupus. The group is 
        coordinated by the NIAMS and includes participation from nine 
        other NIH Institutes and Centers.
  --The NIAID chairs the NIH Autoimmune Diseases Coordinating 
        Committee, established by the Congress in fiscal year 1998 to 
        increase collaboration and facilitate coordination of 
        autoimmune diseases research among 21 NIH Institutes and 
        Centers (ICs), other Federal agencies, and private health and 
        patient advocacy groups.
  --In September 2010, the NIAMS, the National Cancer Institute (NCI), 
        the NIAID, and the NIH Office of Research on Women's Health 
        (ORWH) hosted a 2-day scientific meeting in Bethesda, Maryland, 
        ``Systemic Lupus Erythematosus: From Mouse Models to Human 
        Disease and Treatment.'' Clinicians and basic scientists from a 
        variety of disciplines came together to discuss the clinical 
        and molecular similarities and differences seen in human 
        disease and animal models. Participants also discussed advances 
        in lupus genetics, challenges and advances in the treatment of 
        lupus, and emerging areas warranting further study.
  --The Autoimmunity Centers of Excellence (ACEs), sponsored by the 
        NIAID, the NIDDK, the NIAMS, the National Institute of 
        Neurological Disorders and Stroke (NINDS), and the ORWH, 
        conduct collaborative research on autoimmune diseases, 
        including lupus. This research includes clinical trials of 
        immunomodulatory therapies and associated studies to understand 
        the mechanism of disease and therapeutic effects.
  --The Human Leukocyte Antigen (HLA) Region Genomics in Immune-
        Mediated Diseases Consortium, a cooperative research group 
        sponsored by the NIAID and the NINDS, focuses on defining the 
        association between variations in the HLA genetic region and 
        immune-mediated diseases, including lupus.
  --The Cooperative Study Group for Autoimmune Disease Prevention, 
        sponsored by the NIAID, the NIDDK, and the Juvenile Diabetes 
        Research Foundation International, focuses on research for the 
        prevention of human autoimmune diseases, including lupus. 
        Projects include the creation of improved models of disease 
        pathogenesis and therapy to better understand immune mechanisms 
        that will provide opportunities for prevention strategies.
  --The NIDDK and the NIAMS organized an April 2010 meeting, ``Novel 
        Therapies to Enhance ESRD (End Stage Renal Disease) Patient 
        Survival,'' which included a session on ``Lessons for 
        Nephrologists from Lupus.'' The NIDDK is planning a meeting in 
        mid-2012 that will focus on glomerular disease, including that 
        arising from lupus.
  --The NIDDK-supported Chronic Kidney Disease Biomarkers Consortium--
        which seeks to discover and validate biomarkers for chronic 
        kidney disease--is assessing inflammatory mediators as 
        biomarkers for progression of kidney disease in patients with 
        lupus who have had kidney biopsies. The Consortium will cross-
        validate its findings using a variety of patient cohorts, 
        including those funded by the NIDDK (such as the Chronic Renal 
        Insufficiency Cohort) and other ICs (such as the 
        Atherosclerosis Risk in Communities Study, funded by the 
        NHLBI).
    The proposed NIH NCATS has been designed to catalyze the 
development of innovative methods and technologies that will enhance 
the development, testing, and implementation of diagnostics and 
therapeutics across a wide range of conditions, including diseases such 
as lupus. The NCATS will encourage collaborations across all sectors, 
provide resources to enable therapeutics development, and support and 
enhance training in the relevant translational science disciplines.

         CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) RESEARCH

    Question. COPD is the third leading cause of death in the United 
States, killing approximately 141,075 Americans annually. Despite the 
growing burden of COPD, the United States does not currently have a 
comprehensive public health action plan on the disease. What activities 
are the NIH currently conducting on COPD and what is missing from the 
Federal response? Would a Federal action plan on COPD provide insights 
on how we could better address this leading killer?
    Answer. The NHLBI--the NIH component with primary responsibility 
for lung diseases--supports a wide range of research and education 
activities on COPD. Its programs include basic science and animal 
studies of underlying disease mechanisms; clinical studies of COPD risk 
factors, genetics, molecular and cellular defects, disease progression, 
and co-morbidities; translational studies of pathways and drugs that 
may lead to better treatments; clinical trials; comparative 
effectiveness research; and public and professional educational 
programs to increase awareness of COPD and knowledge about its 
symptoms, diagnosis, and treatment. Several other NIH components, 
including the NCI, the National Institute on Aging (NIA), the National 
Institute on Drug Abuse (NIDA), the National Institute of Environmental 
Health Sciences (NIEHS), the National Institute of General Medical 
Sciences (NIGMS), and the National Institute of Nursing Research 
(NINR), also support research relevant to COPD. For example, the NCI 
and the NHLBI are collaborating on an investigation of lung cancer and 
COPD. The NHLBI also cooperates with a number of other Federal agencies 
on this disease. The NHLBI Long Term Oxygen Treatment Trial is carried 
out in collaboration with CMS. The FDA collaborates with the NHLBI in a 
program called SPIROMICS, which is performing extensive molecular and 
clinical phenotyping of subjects with COPD to indentify biomarkers and 
characterize the heterogeneity in the patient population. VA Medical 
Centers participate in a number of the NHLBI clinical trials in COPD. 
The CDC is a partner in the NHLBI's COPD Learn More Breathe Better 
national public health education campaign. The NHLBI--CDC collaboration 
has led to the introduction of a module on COPD in the Behavioral Risk 
Factor Surveillance System Survey and to a recently released public 
health strategic framework for COPD prevention. Investigators supported 
jointly by the NHLBI and the AHRQ are setting up a large registry for 
comparative effectiveness research. Finally, the reports of the Surgeon 
General on the health effects of smoking are a constant guide for the 
NHLBI programmatic directions for COPD.
    These examples illustrate the extent and diversity of existing 
Government programs related to COPD, the cooperative and complementary 
interactions among Federal agencies in this area, and the central role 
that the NHLBI plays in the Government's efforts to control this 
disease. The NHLBI will continue to provide strong leadership for 
research and education activities to address this growing public health 
epidemic in collaboration with other components of the Federal 
Government. In particular, the NHLBI plans to host a forum of 
representatives from Federal Government agencies in fiscal year 2012 to 
share information regarding current activities related to COPD and to 
discuss opportunities for increasing cooperation among stakeholders and 
enhancing effectiveness of the Federal response to this debilitating 
and deadly disease. Whether a Federal action plan should be developed 
will almost certainly be a topic of discussion at the forum.
clinical trials cooperative group program reorganization impact on the 

                    GYNECOLOGICAL COOPERATIVE GROUP

    Question. The Institute of Medicine (IOM) of the National Academies 
was asked by the National Cancer Institute (NCI) to review the 
Institute's Clinical Trials Cooperative Group Program. One of the 
recommendations from that report is a reorganization of the Cooperative 
Group Structure that would entail restructuring and consolidating some 
of the cooperative groups. We understand that the reorganization may 
merge the Gynecological Cooperative Group (GOG) with the NSABP 
(National Surgical Adjuvant Breast and Bowel Project) and the RTOG 
(Radiation Therapy Oncology Group). Gynecological cancers are generally 
diagnosed by gynecologists and the GOG is the only cooperative group 
that studies gynecological cancers. Is our understanding of the 
reorganization plan for the GOG correct and, if so, what is the 
rationale for the planned merger of the GOG with these other groups? 
What is the scientific basis for it? If not, what is the current plan 
for the GOG? In general, what has been the process for making these 
reorganization decisions, what are the primary considerations and what 
is the timeframe and next steps for finalizing the reorganization 
decisions?
    Answer. For more than 50 years, the NCI has supported a standing 
infrastructure--the NCI Cooperative Group Program--to conduct large 
scale cancer clinical trials across the Nation, with successful 
completion of many important trials that have led to new treatments for 
cancer patients. Over time, however, oncology has evolved into a more 
molecularly based discipline including genetic sub-classification of 
tumors and individualized treatments. Accordingly, the NCI must ensure 
that the Cooperative Groups are optimally situated and well-prepared to 
continue to design, enroll and complete state-of-the-art trials for 
cancer patients.
    In 2009, the NCI commissioned the Institute of Medicine to review 
the Cooperative Group Program in order to gather independent and expert 
perspectives on the state of cancer clinical trials and to obtain 
advice about improvements in the NCI Cooperative Group Program. The IOM 
report ``A National Cancer Trials System for the 21st Century: 
Reinvigorating the NCI Cooperative Group Program'' was issued in April 
2010. The report called for a series of changes to the clinical trials 
program, including restructuring and consolidation of the adult 
Cooperative Groups.
    Transforming the NCI's Cooperative Group System into a highly 
integrated National Clinical Trials Network is one of the Institute's 
major initiatives. Enhancing the scientific basis for the clinical 
trials that the NCI supports is essential if marked improvements in 
cancer diagnosis, prevention, and therapy are to continue unabated. The 
increasing need for molecular screening of large patient populations to 
define categories appropriate for intervention provides an important 
rationale for consolidating the NCI-supported clinical research groups 
into a coordinated network. Furthermore, the NCI's commitment to 
strategic consolidation includes the requirement for a shared, and 
standardized, clinical trials data management IT infrastructure, for a 
facile process by which the phase III clinical trials portfolio is 
prioritized, and for the conduct of clinical investigations that are 
multimodal in nature, and involve understudied and underserved patient 
populations. The NCI's restructured clinical trials network, as 
envisioned, will be organized to move such studies forward both 
efficiently and with the necessary resources to conduct correlative 
scientific investigations capable of increasing the potential of these 
trials to change current medical practice.
    In addition to the ability to screen large patient populations, a 
coordinated network of a smaller number of consolidated Cooperative 
Groups will be better able to prioritize specific trials across all 
disease areas and to efficiently develop and complete multicenter 
trials. Consolidation will also enable optimal use of crucial 
biospecimens from the NCI-supported clinical trials. Finally, 
consolidation will address current disincentives to study less common 
diseases or to enroll patients to another Cooperative Group's trials.
    The NCI began a discussion with the Cooperative Group Chairs in 
November 2010 about changes to the Group structure and has participated 
in multiple discussions with the public. Throughout the process, the 
NCI has been--and remains--committed to having an open dialogue about 
changes to the Cooperative Group Program. The NCI has not dictated 
mergers among groups and instead has encouraged groups to voluntarily 
consolidate on their own. The Gynecological Oncology Group (GOG), the 
National Surgical Adjuvant Breast and Bowel Project (NSABP), and the 
Radiation Therapy Oncology Group (RTOG) have entered negotiations about 
consolidation, and as background for those discussions, the NCI program 
leadership met with the GOG Chair in May 2011 to discuss GOG concerns 
and to provide assurances that funding for gynecological cancers will 
be protected. The NCI expects that consolidation will greatly 
strengthen the overall program and will provide each of the 
consolidated Cooperative Groups with unique capabilities and a greatly 
expanded network of clinical sites to recruit patients for trials 
across the entire program.
    Since December 2010, the NCI has been gathering input from 
stakeholders and the cancer community about the plans to restructure 
the program. The comment period will close in July 2011, at which point 
the NCI will develop a concept proposal about the new structure and 
proceed with the NCI leadership review and presentation to the Board of 
Scientific Advisors in November 2011. The Funding Opportunity 
Announcement for the new Clinical Trials Program will be developed over 
the next several months, and released in July 2012. Applications will 
be accepted in November 2012 and reviewed over the next few months, 
with the consolidated Cooperative Groups being funded in fiscal year 
2014.

                            CREATION OF SUAA

    Question. Based on recommendations from the Scientific Management 
Review Board, the NIH has been considering the formation of a single 
institute that would be devoted to research related to substance use, 
abuse and addiction. The focus at the NIH seems to have turned away 
from this reorganization as attention has shifted to the creation of 
the NCATS. Is the NIH still considering the formation of this institute 
and, if so, what is the latest thinking on the creation of such an 
institute? What is the process and timeframe for making a decision and 
developing a plan?
    Answer. The NIH is actively considering the formation of a single 
Institute that will focus on substance use, abuse, and addiction-
related research. After receiving the SMRB recommendations, Dr. Collins 
formed a Task Force of scientific experts to begin a comprehensive 
review of the NIH substance use, abuse, and addiction research 
portfolio. The Task Force has met with subject matter experts from 
across the NIH to gain a better understanding of the breadth and 
diversity of NIH's substance use, abuse, and addiction portfolio. This 
review has made it clear that this portfolio is very complex and taken 
together with the administrative steps that would be required to 
implement a reorganization of this magnitude, we determined that 
additional time would be advantageous. Additionally, during the last 
few months, many stakeholders have requested additional input into the 
development of the scientific plan for the new Institute.
    The NIH will continue to analyze our substance use, abuse, and 
addiction portfolio to provide a framework for a new proposed 
Institute. We will also develop a new scientific strategic plan to 
provide a framework for substance, use, abuse, and addiction-related 
research at NIH. This scientific strategic plan will be directed by the 
relevant Institute or Center Directors and will include extensive 
consultation with stakeholders, including scientists, patients, and the 
community, in addition to soliciting information from the Advisory 
Councils of the potentially affected Institutes and Centers. It is our 
intent to release the portfolio integration plan and the scientific 
strategic plan in the fall of 2012 for public comment, obtaining the 
Secretary's formal approval in December 2012 with the ultimate goal of 
notifying Congress through inclusion in the proposed reorganization in 
the fiscal year 2014 President's budget and standing up the new 
Institute at the beginning of fiscal year 2014 (October 1, 2013).

               USE OF CHIMPANZEES IN BIOMEDICAL RESEARCH

    Question. In response to a request from the NIH, the Institute of 
Medicine (IOM) is conducting a study on the use of chimpanzees in 
biomedical and behavioral research. The study will assess the current 
and anticipated uses of chimpanzees in the NIH research and determine 
whether chimpanzees are and will be necessary for research needed to 
advance public health. The IOM is expected to release the report by the 
end of this year, in December 2011. Some interest groups have suggested 
that a moratorium be put in place on new funding for invasive research 
using chimpanzees pending the release of the IOM report. What would be 
the impacts of this type of temporary moratorium on the NIH research?
    Answer. NIH appreciates the Senator's continued interest in the use 
of chimpanzees in research. As you know, chimpanzees have been used in 
important research such as key studies on hepatitis, malaria, and 
vaccine research. The Senator wisely requested that NIH initiate an in-
depth analysis to be performed by the Institute of Medicine (IOM) to 
assess the scientific need for the continued use of chimpanzees in 
biomedical research. The NIH has followed this advice and anticipates a 
thoughtful analysis and rigorous review that will be a valuable input 
as NIH charts the future course for the use of chimpanzees in research.
    In the interim, while the IOM study is ongoing, we believe it would 
be unwise to make any abrupt changes in our primate research programs.  
Therefore, we think it best to await the IOM report before making 
decisions that could have potentially far reaching implications.
                                 ______
                                 
            Questions Submitted by Senator Daniel K. Inouye

  THE NATIONAL INSTITUTES OF HEALTH (NIH) RESEARCH SUPPORT TO HAWAII 
                         ACADEMIC INSTITUTIONS

    Question. Over the years the subcommittee has urged the NIH to pay 
particular attention to developing a cadre of scientific investigators 
from rural America and in the case of Hawaii, from the neighbor 
islands. This month the College of Pharmacy at the University of Hawaii 
at Hilo will graduate its first class and I appreciate the ongoing 
efforts by the leadership of several of your Institutes to ensure that 
basic research infrastructure will be made available for their faculty 
and students. In order to attract the next generation of scientists, it 
is absolutely necessary that they be exposed to caring mentors and the 
joy of scientific inquiry in their early academic years. Those of us 
who represent rural America appreciate how difficult it can be to 
provide this critical nurturing experience, especially when bright high 
school students and undergraduate students have to face significant 
transportation barriers, such as exist in an island State. At this 
time, I would appreciate receiving a report detailing the extent to 
which your Institutes have been able to provide scientific resources to 
Hawaii, and particularly to the educational campuses on the various 
islands.
    Answer. The NIH has provided considerable support to Hawaii in an 
effort to ensure that Native Hawaiian and other Pacific Islanders have 
access to the clinical benefits of the NIH research. While research and 
training investments represent the majority of the NIH support to 
institutions in Hawaii, technical assistance to Hawaiian institutions 
has also been important. Periodically over the past decade, the NIH 
through the Office of Policy for Extramural Research Administration 
(OPERA) has provided workshops in Hawaii on the topics of the NIH 
policies, grant writing skills, and human subjects research issues 
including adverse event reporting, vulnerabilities of pediatric 
populations, and cultural issues involving Native Hawaiians 
participating in research studies. Also, the Office of Laboratory 
Animal Welfare (OLAW) presented several comprehensive overviews of the 
laws, regulations, and policies that govern the humane care and use of 
laboratory animals.
    The breadth of the research enterprise in Hawaii is quite 
impressive. In fiscal year 2010, more than 17 of the 27 NIH Institutes 
and Centers have provided support for academic institutions to conduct 
research activities ranging from basic biomedical science to behavioral 
interventions. For example, Chaminade University has a National 
Institute on Minority Health and Health Disparities (NIMHD) Building 
Research Infrastructure and Capacity grant which supports renovations, 
research training, student academic enrichment programs, and junior 
faculty career development activities. The University of Hawaii Hilo 
has received funding from the National Institute on Drug Abuse (NIDA) 
for the mentoring of clinical investigators and to conduct patient-
oriented mental health services research, including post-traumatic 
stress disorder. The National Institute on Alcohol Abuse and Alcoholism 
(NIAAA) is supporting a project to develop research capabilities in the 
area of substance use and indigenous youth populations (e.g., Native 
Hawaiian) at Hawaii Pacific University.
    The University of Hawaii Manoa plays a pivotal role since it has 
the most robust research enterprise of all the Hawaiian institutions of 
higher education. They have received over 70 NIH awards over the past 
year. The NIMHD Center of Excellence, Partnerships for Cardiometabolic 
Disparities in Native and Pacific Peoples, has a focus on 
cardiometabolic health and eliminating health disparities among Native 
Hawaiians and other Pacific Islanders including Filipinos, Samoans, and 
Tongans. The Cancer Research Center of Hawaii is an NCI-designated 
Clinical Cancer Center and is the only such institution in the State of 
Hawaii. Moreover, the University of Hawaii Manoa Research Centers in 
Minority Institutions (RCMI) Multidisciplinary and Translational 
Research Infrastructure Expansion in Hawaii serves as the integrated 
``home'' for clinical and translational science in the State of Hawaii. 
In addition, Hawaiian small business concerns have received NIH support 
for innovative ideas to improve health through the NIH Small Business 
Innovative Research and Small Business Technology Transfer programs. 
For example, Hawaii Biotech is taking the knowledge gained through its 
dengue fever and West Nile virus vaccine programs and applying it to 
tick-borne encephalitis. This project, Recombinant Subunit Vaccine for 
Tick-Borne Encephalitis, addresses an important unmet biodefense need 
within the United States since there is no registered tick-borne 
encephalitis vaccine.
    The NIH is pleased to be able to support biomedical research and 
student training programs to help further the health of Native 
Hawaiians and other Pacific Islanders. Recent discussions between the 
NIH Deputy Director and several faculity at the University of Hawaii 
Hilo may help identify additional gaps that could be filled through the 
NIH-University partnerships.
    Below is a list of all the NIH awards to Hawaiian institutions in 
fiscal year 2010.

                                       FISCAL YEAR 2010 HAWAII NIH AWARDS
----------------------------------------------------------------------------------------------------------------
        Organization name              Grant number        Institute/center              Project title
----------------------------------------------------------------------------------------------------------------
CARDAX PHARMACEUTICALS, INC......  4R44AA018922-02.....  NIAAA..............  Heptax for Alcoholic Liver Disease
CHAMINADE UNIVERSITY OF HONOLULU.  1P20MD006084-01.....  NIMHD..............  Chaminade University BRIC Project
EAST-WEST CENTER.................  5R01HD042474-06.....  NICHD..............  Innovations in Early Life Course
                                                                               Transitions
HAWAII BIOTECH, INC..............  5R44AI055225-04.....  NIAID..............  Recombinant Subunit Vaccine For
                                                                               Tick-Borne Encephalitis
HAWAII PACIFIC UNIVERSITY........  3K01DA019884-04S1...  NIDA...............  Ecological Factors and Drug Use of
                                                                               Native Hawaiian Youth
HAWAII PACIFIC UNIVERSITY........  5K01DA019884-05.....  NIDA...............  Ecological Factors and Drug Use of
                                                                               Native Hawaiian Youth
KUAKINI MEDICAL CENTER...........  5U01AG017155-10.....  NIA................  Epidemiology of Aging and
                                                                               Dementia--Autopsy Research
KUAKINI MEDICAL CENTER...........  5U01AG019349-09.....  NIA................  Epidemiology of Brain Aging in the
                                                                               Very Old
KUAKINI MEDICAL CENTER...........  3R01AG027060-04S1...  NIA................  Defining the Healthy Aging
                                                                               Phenotype
NEUROBEHAVIORAL RESEARCH, INC....  5R01AA013659-08.....  NIAAA..............  Brain Morbidity in Treatment--
                                                                               Naive Alcoholics
NEUROBEHAVIORAL RESEARCH, INC....  5R01AA016944-03.....  NIAAA..............  Long-Term Abstinence Clinical
                                                                               Issues and CNS Disinhibition
NEUROBEHAVIORAL RESEARCH, INC....  5R01AA016303-04.....  NIAAA..............  Effects of heavy alcohol abuse on
                                                                               adolescent brain structure and
                                                                               function
PACIFIC HEALTH RESEARCH INSTITUTE  5U10NS044448-08.....  NINDS..............  Parkinson's Disease
                                                                               Neuroprotection Trial: Hawaii
                                                                               Center
PACIFIC HEALTH RESEARCH/EDUCATION  3U10NS044448-09S1...  NINDS..............  Parkinson's Disease
 INST.                                                                         Neuroprotection Trial: Hawaii
                                                                               Center
PACIFIC HEALTH RESEARCH/EDUCATION  3R01NS041265-10S1...  NINDS..............  Risk Factors for Pathologic
 INST.                                                                         Markers of Parkinson Disease
PACIFIC HEALTH RESEARCH/EDUCATION  6U10NS044448-09.....  NINDS..............  Parkinson's Disease
 INST.                                                                         Neuroprotection Trial: Hawaii
                                                                               Center
PACIFIC HEALTH RESEARCH/EDUCATION  1R01DK089347-01.....  NIDDK..............  Reducing Cost-Related Medication
 INST.                                                                         Nonadherence in Persons with
                                                                               Diabetes
PANTHERA BIOPHARMA, LLC..........  5U01AI078067-03.....  NIAID..............  Antidotes to Anthrax Lethal Factor
                                                                               Intoxication
PAPA OLA LOKAHI..................  3U01CA114630-05S3...  NCI................  IMI HALE NATIVE HAWAIIAN CANCER
                                                                               NETWORK
PAPA OLA LOKAHI..................  1U54CA153459-01.....  NCI................  IMI HALE NATIVE HAWAIIAN CANCER
                                                                               NETWORK
PAPA OLA LOKAHI..................  3U01CA114630-05S4...  NCI................  IMI HALE NATIVE HAWAIIAN CANCER
                                                                               NETWORK
QUEEN'S MEDICAL CENTER...........  5R01GM063954-08.....  NIGMS..............  Molecular and functional
                                                                               properties of the TRPM2 catioin
                                                                               channel
QUEEN'S MEDICAL CENTER...........  5R21CA139687-02.....  NCI................  Treatment Effects on Tumor 18F-
                                                                               Choline Metabolism in Advanced
                                                                               Prostate Cancer
QUEEN'S MEDICAL CENTER...........  5R01GM080555-03.....  NIGMS..............  Molecular components of the store-
                                                                               operated CRAC channel
UNIVERSITY OF HAWAII AT HILO.....  5K24MH074468-05.....  NIMHD..............  Mentoring/Career Development in
                                                                               PTSD Services Research
UNIVERSITY OF HAWAII AT MANOA....  2P20RR016467-09A1...  NCRR...............  INBRE II: Hawaii Statewide
                                                                               Research & Education Partnership
                                                                               (HSREP)
UNIVERSITY OF HAWAII AT MANOA....  3R01NS063932-03S1...  NINDS..............  HIV and Global Drug Therapies:
                                                                               Peripheral Neuropathy
                                                                               Complications and Mechanisms
UNIVERSITY OF HAWAII AT MANOA....  5R01NS053345-05.....  NINDS..............  HIV-1 Proviral DNA and Monocyte
                                                                               Phenotype in Relation to
                                                                               Neurocognitive Function
UNIVERSITY OF HAWAII AT MANOA....  5U54NS056883-04.....  NINDS..............  Imaging Studies in Neurotoxicity
                                                                               and Neurodevelopment
UNIVERSITY OF HAWAII AT MANOA....  5R01NS063932-03.....  NINDS..............  HIV and Global Drug Therapies:
                                                                               Peripheral Neuropathy
                                                                               Complications and Mechanisms
UNIVERSITY OF HAWAII AT MANOA....  5R01NS053359-04.....  NINDS..............  HIV-1 Specific Immune Responses in
                                                                               Thai Individuals with HIV
                                                                               Dementia
UNIVERSITY OF HAWAII AT MANOA....  5P20NR010671-04.....  NINR...............  Center for 'Ohana Self-Management
                                                                               of Chronic Illnesses Hawaii
                                                                               (COSMCI0): Building
UNIVERSITY OF HAWAII AT MANOA....  5R01MH081845-02.....  NIMH...............  The Genetic Control of Social
                                                                               Behavior in the Mouse
UNIVERSITY OF HAWAII AT MANOA....  5R01MH079717-02.....  NIMH...............  Modeling monocyte and macrophage
                                                                               based gene therapy for neuroAIDS
UNIVERSITY OF HAWAII AT MANOA....  1R01EB011517-01.....  NIBIB..............  Spectral Spatial RF Pulses for
                                                                               Gradient Echo fMRI
UNIVERSITY OF HAWAII AT MANOA....  5R24MD001660-06.....  NIMHD..............  PILI 'Ohana Project: Partnerships
                                                                               to Overcome Obesity Disparities
                                                                               in Hawai'i
UNIVERSITY OF HAWAII AT MANOA....  5R01CA115614-04.....  NCI................  Physical Activity in Women with
                                                                               Infants
UNIVERSITY OF HAWAII AT MANOA....  1U13HD063139-01.....  NICHD..............  Community-Based Capacity Building:
                                                                               Academic-Community Partnerships
                                                                               Using Partici
UNIVERSITY OF HAWAII AT MANOA....  5G11HD054969-04.....  NICHD..............  Office of Research Development
                                                                               (EARDA)
UNIVERSITY OF HAWAII AT MANOA....  5F32HD055000-03.....  NICHD..............  Origins of neuronal patterning in
                                                                               animal development
UNIVERSITY OF HAWAII AT MANOA....  2T34GM007684-29A1...  NIGMS..............  Minority Access to Research
                                                                               Careers
UNIVERSITY OF HAWAII AT MANOA....  1R01GM093116-01.....  NIGMS..............  Gene regulatory network evolution
                                                                               and the origin of biological
                                                                               novelties
UNIVERSITY OF HAWAII AT MANOA....  1P41GM094091-01.....  NIGMS..............  Accessing Cyanobacterial Chemical
                                                                               Diversity: A Unique Natural
                                                                               Product Library
UNIVERSITY OF HAWAII AT MANOA....  5R01GM083158-03.....  NIGMS..............  Transposon Based Mammalian
                                                                               Transgenesis and Transfection
UNIVERSITY OF HAWAII AT MANOA....  1R01GM088266-01A1...  NIGMS..............  RSK-2 regulates integrin-mediated
                                                                               adhesion and migration
UNIVERSITY OF HAWAII AT MANOA....  1K01DK090091-01.....  NIDDK..............  Neighborhood Characteristics and
                                                                               Diabetes Incidence in the
                                                                               Multiethnic Cohort Stu
UNIVERSITY OF HAWAII AT MANOA....  5R25DK078386-04.....  NIDDK..............  High School Students STEP-UP To
                                                                               Biomedical Research
UNIVERSITY OF HAWAII AT MANOA....  5R01DK079684-04.....  NIDDK..............  Multimedia intervention to
                                                                               motivate ethnic teens to be
                                                                               designated donors
UNIVERSITY OF HAWAII AT MANOA....  3U10CA063844-17S1...  NCI................  Hawaii Minority-Based Clinical
                                                                               Community Oncology Program
UNIVERSITY OF HAWAII AT MANOA....  5P01CA114047-05.....  NCI................  Pathogenesis of mesothelioma
UNIVERSITY OF HAWAII AT MANOA....  5R01CA058598-12.....  NCI................  Collaborative Genetic Study of
                                                                               Ovarian Cancer Risk
UNIVERSITY OF HAWAII AT MANOA....  5R01CA120799-04.....  NCI................  Testing Alternative Stage Models
                                                                               of Smoking Cessation: An
                                                                               Intervention Study
UNIVERSITY OF HAWAII AT MANOA....  5R37CA054281-18.....  NCI................  Multiethnic Cohort Study of Diet
                                                                               and Cancer
UNIVERSITY OF HAWAII AT MANOA....  1R03CA150041-01.....  NCI................  Urinary Estrogen Metabolites in a
                                                                               2-year Soy Trial Among
                                                                               Premenopausal Women
UNIVERSITY OF HAWAII AT MANOA....  3U54CA143727-02S1...  NCI................  University of Guam/Cancer Research
                                                                               Center of Hawaii Partnership (1
                                                                               of 2)
UNIVERSITY OF HAWAII AT MANOA....  3P30CA071789-12S9...  NCI................  Cancer Research Center of Hawaii
UNIVERSITY OF HAWAII AT MANOA....  3P30CA071789-12S8...  NCI................  Cancer Research Center of Hawaii
UNIVERSITY OF HAWAII AT MANOA....  5U24CA074806-12.....  NCI................  The Colon Cancer Family Registry:
                                                                               Hawaii
UNIVERSITY OF HAWAII AT MANOA....  1R01CA153154-01.....  NCI................  Self-Control as a Moderator for
                                                                               Effects of Mass Media on
                                                                               Adolescent Substance Use
UNIVERSITY OF HAWAII AT MANOA....  3U24CA074806-11S1...  NCI................  The Colon Cancer Family Registry:
                                                                               Hawaii
UNIVERSITY OF HAWAII AT MANOA....  7R01CA124687-03.....  NCI................  The Sphingolipid Pathway in Colon
                                                                               Cancer Chemoprevention
UNIVERSITY OF HAWAII AT MANOA....  2U10CA063844-17.....  NCI................  Hawaii Minority-Based Clinical
                                                                               Community Oncology Program
UNIVERSITY OF HAWAII AT MANOA....  5R21AT004844-02.....  NCCAM..............  Mechanisms by which selenium
                                                                               influences T helper cells during
                                                                               immune responses
UNIVERSITY OF HAWAII AT MANOA....  5R21AT005139-02.....  NCCAM..............  Exploratory Studies on the Anti-
                                                                               Breast Cancer Function of Bamboo
                                                                               Extract
UNIVERSITY OF HAWAII AT MANOA....  7R01AI054128-06.....  NIAID..............  Mechansim of activation of innate
                                                                               immunity by ISS-DNA
UNIVERSITY OF HAWAII AT MANOA....  5R01AI075057-03.....  NIAID..............  Intraspecies Transmission and
                                                                               Infectivity of Insectivore-Borne
                                                                               Hantaviruses
UNIVERSITY OF HAWAII AT MANOA....  5R01AI071160-04.....  NIAID..............  Malarial Immunity in Pregnant
                                                                               Cameroonian Women
UNIVERSITY OF HAWAII AT MANOA....  1R01AI089999-01.....  NIAID..............  Selenoprotein K modulates calcium-
                                                                               dependent signaling in immune
                                                                               cells
UNIVERSITY OF HAWAII AT MANOA....  5R01AI074554-03.....  NIAID..............  Global HIV Drug Therapies and
                                                                               Mitochondrial Complications and
                                                                               Mechanisms
UNIVERSITY OF HAWAII AT MANOA....  5U01HG004802-03.....  NHGRI..............  Epidemiology of Putative Causal
                                                                               Variants in the Multiethnic
                                                                               Cohort
UNIVERSITY OF HAWAII AT MANOA....  5R01DA021146-04.....  NIDA...............  RGR-based motion tracking for real-
                                                                               time adaptive MR imaging and
                                                                               spectroscopy
UNIVERSITY OF HAWAII AT MANOA....  5R01DA021856-04.....  NIDA...............  The Project Success Model:
                                                                               Evaluation of a Tiered
                                                                               Intervention
UNIVERSITY OF HAWAII AT MANOA....  5K02DA020569-05.....  NIDA...............  Parallel MRI for Substance Abuse
                                                                               Research
UNIVERSITY OF HAWAII AT MANOA....  5K23DA020801-05.....  NIDA...............  Neurodevelopment of
                                                                               Methamphetamine Exposed Children
UNIVERSITY OF HAWAII AT MANOA....  5R01DA019912-04.....  NIDA...............  Parallel MRI for High Field
                                                                               Neuroimaging
UNIVERSITY OF HAWAII AT MANOA....  5K24DA016170-07.....  NIDA...............  Neuroimaging and Mentoring in Drug
                                                                               Abuse Research
UNIVERSITY OF HAWAII AT MANOA....  1R24DA027318-01.....  NIDA...............  Factors for enhanced neurotoxicity
                                                                               in methamphetamine abuse in HIV
                                                                               infection
UNIVERSITY OF HAWAII AT MANOA....  5K01DA021203-04.....  NIDA...............  Impact of Marijuana Exposure on
                                                                               Brain Maturation
UNIVERSITY OF HAWAII AT MANOA....  3R25RR024281-03S1...  NCRR...............  Pacific Education and Research for
                                                                               Leadership in Science (PEARLS)
UNIVERSITY OF HAWAII AT MANOA....  5P20RR024206-03.....  NCRR...............  Institute for Biogenesis Research:
                                                                               COBRE
UNIVERSITY OF HAWAII AT MANOA....  5P20RR016453-09.....  NCRR...............  COBRE: Center for Cardiovascular
                                                                               Research
UNIVERSITY OF HAWAII AT MANOA....  5R25CA090956-08.....  NCI................  Nutritional & Behavioral Cancer
                                                                               Prevention in a Multiethnic
                                                                               Population
UNIVERSITY OF HAWAII AT MANOA....  5R01CA126895-03.....  NCI................  Whole Genome Scan for Modifier
                                                                               Genes in Colorectal Cancer
UNIVERSITY OF HAWAII AT MANOA....  5R01CA129063-03.....  NCI................  Inflammation and Innate Immunity
                                                                               Genes and Colorectal Cancer Risk
UNIVERSITY OF HAWAII AT MANOA....  5R03CA135699-02.....  NCI................  A pooled analysis of mammographic
                                                                               density and breast cancer risk
UNIVERSITY OF HAWAII AT MANOA....  5R01CA140636-02.....  NCI................  Characterizing Mitochondrial DNA
                                                                               Susceptibility to Breast,
                                                                               Colorectal, and Prosta
UNIVERSITY OF HAWAII AT MANOA....  5R01CA080843-09.....  NCI................  Effects of Soy on Estrogens in
                                                                               Breast Fluid and Urine
UNIVERSITY OF HAWAII AT MANOA....  5U54CA143727-02.....  NCI................  University of Guam/Cancer Research
                                                                               Center of Hawaii Partnership (1
                                                                               of 2)
UNIVERSITY OF HAWAII AT MANOA....  5K23HL088981-03.....  NHLBI..............  Cardiovascular autonomic function
                                                                               in HIV virologic failure
UNIVERSITY OF HAWAII AT MANOA....  5R01HL095135-03.....  NHLBI..............  Role of Oxidative Stress and
                                                                               Inflammation in HIV
                                                                               Cardiovascular Risk
UNIVERSITY OF HAWAII AT MANOA....  1R01HL098423-01A1...  NHLBI..............  Role of mTOR in the diabetic heart
UNIVERSITY OF HAWAII AT MANOA....  5UH1HL073449-07.....  NHLBI..............  University of Hawaii Research
                                                                               Scientist Award in Molecular
                                                                               Cardiology
UNIVERSITY OF HAWAII AT MANOA....  5R21HL087289-02.....  NHLBI..............  Pseudoxanthoma elasticum: Elastic
                                                                               fibers alterations and
                                                                               characterization of seru
UNIVERSITY OF HAWAII AT MANOA....  5R01HL081863-05.....  NHLBI..............  Rho kinase in immune-mediated
                                                                               atherosclerosis
UNIVERSITY OF HAWAII AT MANOA....  5R01AI068525-05.....  NIAID..............  Role of macrophages in HIV
                                                                               Lipoatrophy
UNIVERSITY OF HAWAII AT MANOA....  5G12RR003061-25.....  NCRR...............  Research Outcomes Accelerating
                                                                               Discoveries for Medical
                                                                               Applications and Practice
UNIVERSITY OF HAWAII AT MANOA....  1R01HD060722-01A1...  NICHD..............  Contribution of Sperm Nucleus to
                                                                               Paternal DNA Replication
UNIVERSITY OF HAWAII AT MANOA....  5R21AG032405-02.....  NIA................  A Needle in a Haystack: New
                                                                               approaches to Alzheimer's Drug
                                                                               Discovery from Natural
UNIVERSITY OF HAWAII AT MANOA....  2P20RR018727-06A1...  NCRR...............  Pacific Center for Emerging
                                                                               Infectious Diseases Research
UNIVERSITY OF HAWAII AT MANOA....  5P20MD000173-09.....  NIMHD..............  Partnerships for Cardiometabolic
                                                                               Disparities in Native and Pacific
                                                                               Peoples
UNIVERSITY OF HAWAII AT MANOA....  5R01GM057873-11.....  NIGMS..............  Cyclopentannelation in Total
                                                                               Synthesis
UNIVERSITY OF HAWAII AT MANOA....  1U54RR026136-01A1...  NCRR...............  RCMI Multidisciplinary And
                                                                               Translational Research
                                                                               Infrastructure EXpansion Hawaii
UNIVERSITY OF HAWAII AT MANOA....  5R25RR024281-03.....  NCRR...............  Pacific Education and Research for
                                                                               Leadership in Science (PEARLS)
----------------------------------------------------------------------------------------------------------------

 THE NATIONAL INSTITUTE OF NURSING RESEARCH (NINR) SUPPORT FOR END-OF-
               LIFE CARE AND HEALTH DISPARITIES RESEARCH

    Question. The NINR will soon be celebrating its 25th anniversary. 
The late Senator Quentin Burdick and I were active in establishing the 
original Center and I am confident he would share my enthusiasm for how 
nicely it has matured over the years. At this time I would appreciate 
an update on the extent to which the NINR has been able to co-fund 
various initiatives with other NIH Institutes, particularly in the 
areas of end-of-life issues and racial and geographical disparities.
    Answer. Improving palliative and end-of-life care and eliminating 
health disparities are critical components of the NINR's research 
mission. Consistent with this mission, as well as the Institute's 
longstanding practice of extensive collaboration with other NIH ICs, 
the NINR co-funds numerous scientific efforts with other ICs focused on 
these two important topics.
    As the lead NIH Institute on issues related to end-of-life care 
research, the NINR, with support from partners across the NIH, will 
convene a forum on August 10-12, 2011, entitled ``The Science of 
Compassion: Future Directions in End-of-Life and Palliative Care.'' A 
part of the NINR's 25th Anniversary commemoration, this forum is 
intended to energize and mobilize palliative and end-of-life care 
research and to draw attention to palliative and end-of-life care 
processes, options available to patients and their families, and the 
healthcare community's obligation to address these complex needs. This 
event is co-sponsored by the following NIH partners: National Institute 
on Aging (NIA), Office of Rare Diseases Research, Office of Research on 
Women's Health, National Center for Complementary and Alternative 
Medicine, and the NIH Clinical Center Department of Bioethics.
    In addition, the NINR and the NIH Common Fund recently awarded $7.1 
million in funding provided by the American Recovery and Reinvestment 
Act to support a Palliative Care Research Cooperative (PCRC), a multi-
institution effort to conduct collaborative research on palliative and 
end-of-life care. The PCRC will bring together experienced, 
multidisciplinary investigators to facilitate innovative, high-impact, 
clinically useful palliative care research to inform practice and 
health policy. The PCRC will address challenges associated with 
conducting research with individuals with life-limiting conditions, and 
could lead to significant improvements in the evidence base for 
palliative and end-of-life care.
    NINR also collaborates with other ICs to support basic, clinical, 
and translational research to address health disparities across the 
life span. The NINR currently co-funds an initiative focused on 
reducing health disparities in minority and underserved children, 
including children from: racial/ethnic minority groups; rural and low-
income populations; and geographically isolated locations. The NINR, 
and other Institutes, have supported various important projects under 
this initiative. For example, the NINR-supported investigators are 
testing interventions to improve the well-being of African American, 
Hispanic, and White families where grandmothers are raising 
grandchildren. These custodial grand-families are at high risk for 
psychological difficulties and limited access to needed services. This 
initiative is co-funded with the following NIH Institutes: National 
Institute of Child Health and Human Development; National Heart, Lung, 
and Blood Institute; National Institute on Alcohol Abuse and 
Alcoholism; and the National Institute on Deafness and Other 
Communication Disorders.
    Additionally, researchers funded by the NINR and the NIA developed 
the Resources for Enhancing Alzheimer's Caregivers Health (REACH) II 
program which teaches caregivers about Alzheimer's disease, managing 
stress, and maintaining their own health. In a large sample of African 
American and White caregivers for Alzheimer's patients, those in the 
REACH II intervention reported better physical, emotional, and overall 
health and had lower scores for depression which contributed to 
reducing caregiving burden. To address the need for support of 
caregivers, particularly in racially/ethnically diverse families, 
multiple efforts across the Federal Government are currently underway 
to implement REACH in the community.

           HEALTH MESSAGES FOR THE NATIVE HAWAIIAN POPULATION

    Question. According to the fiscal year 2012 NIH CJ, the National 
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) 
``supports a robust information dissemination and outreach program to 
distribute research-based information to the public, patients, and 
their healthcare providers.'' The NIAMS supported National 
Multicultural Outreach Initiative ``is creating a sustainable network 
of partners to assist in the development and dissemination of health 
messages and materials for racial and ethnic minority populations.'' 
The Initiative will focus its efforts on reaching many different 
minority/ethnic populations including Native Hawaiians. ``Working with 
existing NIAMS partners, the Institute will develop research-based 
self-care messages and products, and ensure their distribution through 
trusted health and multicultural community channels. The NIAMS 
implemented critical phases of the Initiative in fiscal year 2011, 
namely, the development and pretesting of culturally and linguistically 
appropriate health messages and materials through audience research.''
    The NIAMS and its National Multicultural Outreach Initiative are 
supporting the development of health messages for racial and ethnic 
minority populations. What types of health messages are being developed 
and tested for the Native Hawaiian population?
    Answer. In fiscal year 2011, the NIAMS completed qualitative 
research with members of multicultural communities, including Native 
Hawaiians, to help inform the development of culturally appropriate and 
useful health education products for adults with medical conditions 
affecting the bones, joints, muscles, and skin. The NIAMS conducted a 
total of 18 focus groups (2 with Native Hawaiians), and 20 in-depth 
interviews (2 with Native Hawaiians) to gather feedback from 
individuals on preferences for different message concepts and formats 
for communicating health messages. The information gleaned from this 
audience research will enable the development of tailored products that 
raise awareness about the availability of reliable, research-based 
health information and resources from the NIAMS and partner 
organizations to help patients and their families manage their 
conditions.
    The NIAMS National Multicultural Outreach Initiative relies on the 
guidance and input from its working groups for the development and 
dissemination of health messages and products. These groups are 
comprised of national experts from multicultural communities, and 
include representation from the Native Hawaiian community.

   THE NATIONAL INSTITUTE ON MINORITY HEALTH AND HEALTH DISPARITIES 
             (NIMHD) CENTERS OF EXCELLENCE (COE) IN HAWAII

    Question. The fiscal year 2012 congressional justification states 
that the NIMHD has supported 91 COE sites in 35 States, the District of 
Columbia, Puerto Rico, and the U.S. Virgin Islands. According to the 
CJ, the ``types of institutions are diverse and include Historically 
Black Colleges and Universities, Hispanic-Serving Institutions, Tribal 
Colleges and Universities, Alaskan Native, and Native Hawaiian Serving 
Institutions.'' In fiscal year 2010, the 51 active COEs conducted 
transdisciplinary research on high priority diseases/conditions 
including ``cardiovascular disease, stroke, cancer, diabetes, HIV/AIDS, 
infant mortality, mental health, and obesity that disproportionately 
affect racial/ethnic minority and other health disparity populations.''
    Is the NIMHD currently supporting a COE at a Native Hawaiian 
Serving Institution? What high priority diseases or conditions are the 
focus of research at a COE in a Native Hawaiian Serving Institution?
    Answer. The NIMHD COE represent a scientific platform for 
innovative research projects, research training, and effective 
community engagement to address the health status of health disparity 
populations. The NIMHD has provided funding for a COE at the University 
of Hawaii Manoa since September 2002. This COE, Partnerships for 
Cardiometabolic Disparities in Native and Pacific Peoples, is a 
regional focal point for improving cardiometabolic health and 
eliminating health disparities among Native Hawaiians and other Pacific 
Islanders, including Filipinos, Samoans, and Tongans.
    The primary focus of the COE is obesity and diabetes which are 
known risk factors for cardiovascular disease. Eighty-two percent of 
Native Hawaiians are overweight or obese, which is considerably higher 
than the national average of 53 percent. Pacific Islander women with 
diabetes have a higher risk of myocardial infarction. Through dedicated 
efforts over the years, Partnerships for Cardiometabolic Disparities in 
Native and Pacific Peoples has made significant contributions to the 
improvements in the health of Native Hawaiians and other Pacific 
Islanders.
    In addition, supplemental funding was provided in July 2010 to 
support the establishment of the Comparative Effectiveness Research 
Approaches to Eliminate Cardiometabolic Disparities initiative as part 
of the COE. The intent of the project is to train researchers in 
comparative effectiveness research, to conduct innovative research, to 
establish diabetes and cardiometabolic disease registries, and to 
disseminate research results to communities with health disparities in 
Hawaii.

                 HEREDITARY ANGIODEMA RESEARCH SUPPORT

    Question. Dr. Collins, I would like to thank you for your 
leadership of the National Institutes of Health, including its 
continuing emphasis on rare diseases. As you are aware, the NIH 
provides critical opportunities for research surrounding orphan 
conditions which otherwise may not have an opportunity for significant 
research. Recently, constituents and members of the U.S. Hereditary 
Angioedema Association (USHAEA), based in Honolulu, brought to my 
attention the absence of Federal support since 2009 for hereditary 
angioedema (HAE) research. I would appreciate receiving a report on why 
funding for this disease was eliminated and what your efforts are 
toward reinvigorating hereditary angioedema research support.
    Answer. HAE is a rare genetic disorder. HAE patients suffer from 
swelling of the hands, feet, abdomen, face and/or throat. Especially 
the latter is a major medical emergency that may be fatal. Estimates 
for the prevalence of HAE range from 1 in 10,000 to 1 in 50,000 people 
in the United States.
    In 2009, a number of research projects focusing on hereditary 
angioedema came to a natural end. For example, the most extensive 
project, sponsored by the Eunice Kennedy Shriver National Institute of 
Child Health and Human Development, C1 Inhibitor Gene and Hereditary 
Angioneurotic Edema, was last funded in 2008 after 23 years of research 
and concluded in 2010. The Principal Investigator did not apply for 
renewed funding for this project.
    The National Center of Research Resources (NCRR) funded Mount Sinai 
General Clinical Research Center project: CHANGE Trial (C1-Inhibitor in 
Hereditary Angioedema Nanofiltration Generation Evaluating Efficacy): 
Open-Label Safety/Efficacy Repeat Exposure Study of C1 Esterase 
Inhibitor (Human) in the Treatment of Acute Hereditary Angioedema (HAE) 
Attacks participant visits ended in March 2009 and closed in September 
2009. The results were published in the NEJM in August 2010 (PMID 
20818886). Currently, the NCRR-funded Mount Sinai Clinical and 
Translational Science Award supports the Phase III Randomized Double 
Blind, Placebo controlled Multicenter Study of Icatibant for 
Subcutaneous Injection in Patients with Acute Attacks of Hereditary 
Angioedema.
    The NCRR General Clinical Research Center at the University of 
Texas Medical Branch at Galveston (UTMB) conducted the Randomized, 
Placebo-Controlled, Double-blind Phase II Study of the Safety and 
Efficacy of Recombinant Human C1 Inhibitor for the Treatments of Acute 
Attacks in Patients with Hereditary Angioedema. The study ended in May 
2009.
    The NCRR-funded University of Texas Medical Branch at Galveston 
(UTMB) Clinical and Translational Science Award represents an 
additional site which conducted the Phase III Randomized Double-Blind, 
Placebo-Controlled Multicenter Study of Icatibant for Subcutaneous 
Injection in Patients with Acute Attacks of Hereditary Angioedema 
(HAE). This study was completed in May 2011.
    Currently, we also are supporting three training grants with 
projects investigating HAE, two from National Institute of Allergies 
and Infectious Diseases and one from the National Heart, Lung, and 
Blood Institute. These training grants are critical since they train 
the next generation of investigators. The trainees are expected to 
continue their careers with a research emphasis on HAE. The NIH would 
welcome the opportunity to support meritorious research studies 
focusing on hereditary angioedema (HAE).
    To stimulate future research activities and applications we would 
encourage investigators and advocates of HAE research to submit an 
application for a scientific conference grant. In addition to helping 
to identify research opportunities and needs and develop a research 
agenda and research priorities for HAE, such a conference could create 
significant research interest in this particular rare disease. The 
Office of Rare Diseases Research (ORDR), collaborating with other NIH 
research institutes, would be pleased to confer with the U.S. 
Hereditary Angioedema Association (U.S. HAEA) and interested research 
investigators about your concerns.

                CANCER PREVELANCE AND RESEARCH IN HAWAII

    Question. Over the years the NCI has systematically invested in 
research activities targeting the unfortunately high incidence of 
cancer among my State's Native Hawaiian population. At one point the 
NCI researchers reported that Native Hawaiian women had the highest 
incidence of breast cancer in the world. I am confident that progress 
has been made and would appreciate a report describing the NCI's future 
plans for targeting the special needs of these indigenous people.
    Answer. The NCI funds research that focuses on Native Hawaiian, 
other Pacific Islander, and Asian American populations. These studies 
are supported to illuminate the causes of cancer in these populations; 
to improve screening rates so that when cancer appears, it can be 
treated at an early stage; to increase knowledge about treatment 
options so that patients and their physicians can make more informed 
choices about their care; to fund registries, surveys, and reports that 
generate the latest statistics and inform researchers, policy makers, 
and the public; to support cohorts that provide a population base from 
which to conduct important future research, and ultimately to prevent 
cancers in these populations.
Current Efforts
    The NCI's Prostate, Lung, Colorectal, and Ovarian Cancer Screening 
Trial (PLCO) and National Lung Screening Trial (NLST) studies, with 
more than 200,000 participants, include programs in Hawaii and from 
diverse ethnic populations. At the Pacific Health Research and 
Education Institute in Honolulu, of the 13,200 study participants in 
Hawaii, approximately half were Asians (5,553) and Native Hawaiians and 
other Pacific Islanders (1,053).
    In the area of clinical trial recruitment of minorities, the 
University of Hawaii Minority-Based Community Clinical Oncology Program 
(MB-CCOP), funded since 1994, provides access to the NCI clinical 
trials in cancer prevention, treatment, and control to both children 
and adults.
    The NCI Community Network Program (CNP) Centers address disparities 
at the community level with outreach, research, and training. Two CNPs 
are oriented to Pacific Islanders (Imi Hale and Weaving an Islander 
Network for Cancer Awareness, Research and Training, or WINCART) and 
two other CNPs are focused on underserved Asians (Asian American 
Network for Cancer Awareness, Research, and Training, or AANCART, and 
the Asian Community Cancer Health Disparities Center, or ACCHD).
    National Outreach Program (NOP) supported by the Imi Hale Native 
Hawaiian Cancer Network is designed to reduce cancer incidence and 
mortality among Native Hawaiians by maintaining and expanding an 
infrastructure that:
  --Promotes cancer awareness within Native Hawaiian communities;
  --Provides education and training to develop Native Hawaiian 
        researchers; and
  --Facilitates research that aims to reduce cancer health disparities 
        experienced by Native Hawaiians.
    The Imi Hale Native Hawaiian Cancer Network made progress toward 
reducing cancer incidence and mortality among Native Hawaiians through 
a project, ``Woman to Woman-Micronesians United Lay Educator Program'' 
for Native Hawaiians focused on increasing breast and cervical cancer 
screening. Six months of outreach activities resulted in screening of 
150 women. CNP-Southern California developed culturally tailored 
educational resources specifically for Native Hawaiians and the 
Marshallese, in colorectal cancer screening, which resulted in a 
library of culturally relevant resources. In addition to these primary 
efforts, the CNP Native Hawaiian trainees have submitted 40 grant 
applications and a total of 12 were ranked high enough for funding.
    Imi Hale has a dedicated Community Health Educator, who seeks to 
bridge the gap between the community and the research community by 
developing culturally tailored cancer information. For instance, to 
help women learn to do self-breast exams to detect lumps early, Imi 
published Breast Health Shower Cards in nine languages. In terms of 
breast cancer education, Imi Hale has produced a DVD entitled ``A 
Journey of Hope: When a Young Woman Gets Cancer.'' Seeking creative 
ways to educate women about breast cancer, Imi Hale created a breast 
cancer computer game (http://imihale.org/game/click_to_start.html). In 
addition, a series of brochures for Native Hawaiian breast cancer 
survivors called ``Talking Story Booklets'' has been developed. The 
outreach component works closely with such partners as the five Native 
Hawaiian healthcare Systems positioned on five islands.
  --Imi Hale Clinical partners include: Community Health Centers 
        serving Native Hawaiian clients, the Queen`s Cancer Center and 
        other hospitals, and the State-contracted Breast and Cervical 
        Cancer Control Programs; and
  --Imi Hale Community partners include: Association of Hawaiian Civic 
        Clubs, Hawaii State Tobacco Coalition, Office of Hawaiian 
        Affairs, and other community agencies.
    A Comprehensive Partnership to Reduce Cancer Health Disparities 
Program between the University of Hawaii Cancer Center (UHCC) and the 
University of Guam (UOG) have an NCI-funded partnership with the aim of 
enhancing the awareness of cancer and cancer prevention and ultimately 
reducing the impact of cancer on the population in Hawaii, the 
Territory of Guam and the other U.S.-associated Pacific Island 
territories. The partnership supports projects designed to develop 
culturally appropriate guidelines for tobacco use prevention and 
cessation in youth with the underlying hypothesis that interventions to 
prevent tobacco use are more likely to succeed if they conform to 
culturally relevant guidelines developed with the active participation 
of the target youth themselves. The long-term goal of the community-
based participatory outreach program is to engage the community as 
equal partners in tobacco control and cancer prevention research. The 
partnership also supports investigator-initiated cancer research 
projects that address different aspects of cancers in Hawaii and Guam 
including the development of protocols for studying oral precancerous 
lesions and other health risks among betel nut users in Hawaii, the 
Territory of Guam and the other U.S.-associated Pacific Island 
territories.
    The NCI Community Cancer Centers Program (NCCCP) is designed to 
create a community-based cancer center network to support basic, 
clinical and population-based research initiatives, addressing the full 
cancer care continuum--from prevention, screening, diagnosis, 
treatment, and survivorship through end-of-life care. The NCCCP pilot 
has added the Queen's Medical Center, Honolulu, Hawaii (The Queen's 
Cancer Center) to its 30 hospital network.
Future Research
    The NCI will be launching a program to foster evidence-based 
research, data collection, and analysis within Asian American and 
Pacific Islander (AAPI) populations and subpopulations through a unique 
collaboration with the University of Guam, the University of Hawaii, 
the Pacific Regional Central Cancer Registry, and the Pacific Island 
Cancer Council. The NCI developed the Health Information National 
Trends Survey (HINTS) to monitor changes in the rapidly evolving field 
of health communication by collecting data across the Nation. The 
HINTS-Guam program will pilot test a localized survey instrument geared 
specifically to AAPI populations and subpopulations, including 
Chamorros and other Pacific Islanders living on Guam. Data collected 
from this survey will increase understanding of cancer information 
seeking, experiences, and behaviors (prevention, screening, treatment, 
etc.) among AAPI populations. Discussions have also begun on a HINTS 
pilot project to be conducted in Hawaii.

             KIDNEY DISEASE AND DIABETES RESEARCH IN HAWAII

    Question. It has recently come to my attention that my State's 
Filipino population has an extraordinarily high incidence of kidney 
disease. Similarly, several ethnic groups in Hawaii (including Native 
Hawaiians) have been found to have high incidences of diabetes. 
Accordingly, I would appreciate receiving a report on your efforts to 
develop initiatives targeting these populations, and particularly those 
which would stress prevention and perhaps diet.
    Answer. Data show that Filipinos in Hawaii seem to have a 
disproportionate burden of kidney disease. The NIDDK is naturally very 
concerned about kidney disease in Hawaiians, including the health 
disparity in the Filipino population, and has several initiatives in 
place to address the problem. First, our National Kidney Disease 
Education Program (NKDEP) provides materials that can be used in 
Hawaii's high risk populations. The NKDEP's materials aim to raise 
awareness of the seriousness of kidney disease, the importance of 
testing those at high risk (those with diabetes, high blood pressure, 
or a family history of kidney failure), and the availability of 
treatment to prevent or slow kidney failure. NKDEP's extensive new 
offerings on dietary intervention in chronic kidney disease for 
providers and patients would be particularly useful.
    The National Diabetes Education Program (NDEP) is sponsored by the 
NIDDK and Centers for Disease Control and Prevention (CDC) and includes 
more than 200 partners working together to improve the treatment and 
outcomes for people with diabetes, promote early diagnosis, and prevent 
or delay the onset of type 2 diabetes, a leading cause of kidney 
disease. The NDEP has a major focus on Asian Pacific Islanders; it has 
translated educational materials into Tagalog, one of the languages 
spoken in the Fillipino population. These materials address both 
prevention of diabetes and prevention of complications such as kidney 
disease. The University of Hawaii is a site for the Diabetes Prevention 
Program Outcomes Study, which recently reported data showing durability 
of effect of lifestyle intervention and the drug metformin at 
preventing or delaying onset of type 2 diabetes at 10 years follow-up.
    People whose disease progresses to kidney failure can be treated 
with a kidney transplant, though limitations on available donor organs 
is a chronic problem. The NIDDK's ``Minority Organ Donation Program'' 
initiative supports an investigator at the University of Hawaii, Dr. 
Cheryl Albright, whose research focuses on educating Filipino high 
school students about signing up (on drivers' licenses) to donate 
organs. Students from Honolulu and other smaller Islands (including 
rural areas) are participants. The grant is in the fourth year and 
results are quite encouraging. The Filipino community is very 
interested in kidney transplants, and participated in the original 
National Minority Organ and Tissue Transplant Education Program (http:/
/mottep.org/) to rally the community around kidney donation from 
relatives and friends.
    In another initiative, the NIDDK, in collaboration with the CDC and 
the Indian Health Service, has funded eight Tribal Colleges and 
Universities in the initiative ``Diabetes Education in Tribal 
Schools.'' This effort developed supplemental curricula, to be used in 
K-12 schools in American Indian and Alaska Native communities, about 
prevention and better management of diabetes, the most common cause of 
kidney failure. Although the cultural content is directed primarily 
toward American Indians, some Hawaiian schools participated in piloting 
the curricula. The project is completed and the curricula are being 
fielded in tribal schools. Also, the curricula were distributed to and 
currently are being used in Hawaiian schools, primarily on the Big 
Island of Hawaii.

                STROKE DISPARITIES IN THE UNITED STATES

    Question. I am concerned that stroke apparently remains the number 
two killer in the United States and a major cause of disability. In 
addition, stroke affects some segments and regions of our population 
more than others. I understand that the State of Hawaii ranks 20 out of 
52 highest in our Nation for age-adjusted stroke deaths. Death rates 
from a certain type of stroke (intracerebral hemorrhage) are higher 
among Asians/Pacific Islanders than among Whites. More than 20 percent 
of Native Hawaiians or other Pacific Islanders have high blood 
pressure, a leading risk factor for stroke. Yet, the NIH invests only 1 
percent of its budget on stroke research. What is your Institute doing 
to address the disparities that exist in stroke burden among different 
cultural and racial populations in the United States?
    Answer. Stroke research at the NIH is comprehensive and includes 
research on basic disease mechanisms; epidemiology studies to assess 
stroke risk, occurrence and outcomes in the population; clinical 
research to develop effective prevention and acute treatment 
approaches; and development of strategies for improving recovery and 
rehabilitation in stroke patients. Clinical research in stroke is 
particularly a high priority at the National Institute of Neurological 
Disorders and Stroke (NINDS)--approximately 50 percent of its large 
Phase III trials are on stroke.
    The NINDS also supports major research initiatives aimed at better 
defining stroke risk, incidence and outcomes in the United States and 
among different subpopulations. Collections of population-based data 
help identify and explain health disparities in stroke, and inform the 
development of preventive interventions that target high risk 
populations.
  --In the Reasons for Geographic and Racial Differences in Stroke 
        (REGARDS) study, investigators are exploring the geographical 
        and racial influences on stroke risk in a cohort of about 
        30,000 individuals, about half of whom live in the ``stroke 
        belt'' region of the Southeastern United States. This large 
        study has produced over 70 publications that have led to a 
        better understanding of disparities in stroke in the United 
        States. Data generated from this study continue to help 
        researchers pinpoint why the stroke rate is higher in this 
        region, and among African Americans, and to develop targeted 
        strategies for intervention. Recent data from REGARDS indicated 
        that overall time spent in the stroke belt is more predictive 
        of hypertension--a powerful risk factor for stroke--than is 
        current residence in the stroke belt. Data from the REGARDS 
        study have also revealed that stroke survivors were more likely 
        to have unrecognized hypertension and diabetes.
  --The Stroke Disparities Program is a multi-component program to 
        address major stroke challenges in the African American 
        community. The three projects in this program include:
    --an intervention strategy to increase stroke knowledge and reduce 
            the time from symptom onset to hospital arrival (ASPIRE);
    --an intervention utilizing navigators for secondary stroke 
            prevention that targets adherence to poststroke care 
            (PROTECT DC); and
    --an observational imaging study to better understand racial and 
            ethnic differences in risk, occurrence and outcomes of 
            small brain hemorrhages (DECIPHER).
  --The NOrthern MAnhattan Study (NOMAS) investigators have been 
        following a cohort of stroke-free adults, including whites, 
        African Americans and Caribbean Hispanics in a Northern 
        Manhattan community. Researchers are collecting imaging, 
        biological and neuropsychological data to evaluate the 
        relationship between biological and imaging predictors for 
        stroke, heart attack and death, as well as cognitive decline. 
        Using these markers in combination with other factors such as 
        diet, alcohol use, smoking, and history of peripheral vessel 
        disease, investigators are developing risk factor and cognitive 
        ability assessment tools. Genetic studies involving this and 
        other cohorts, have suggested that there may be genetic 
        susceptibilities underlying left atrium size and 
        atherosclerosis of the carotid arteries that contribute to 
        stroke.
  --BASIC (Brain Attack Surveillance in Corpus Christi) investigators 
        are comparing trends in recurrent stroke, as well as functional 
        and cognitive outcomes following stroke, in 5,000 non-Hispanic 
        whites and Mexican Americans in Corpus Christi, Texas. Data 
        from this study have shown that Mexican Americans with atrial 
        fibrillation are more likely to have recurrent strokes than 
        whites, and the strokes are more likely to be severe. The 
        investigators are also exploring associations between 
        biological and social stroke risk factors, and recently found, 
        for example, that the density of fast food restaurants was 
        associated with neighborhood stroke risk.
  --Ethnic and Racial variation in Intracerebral Hemorrhage (ERICH), a 
        study that was initiated in 2010, will identify differences in 
        intracerebral hemorrhage (ICH) risk factor distribution and 
        outcomes by race and ethnicity. This project will compare 3,000 
        cases of ICH, among African Americans, Hispanics and non-
        Hispanic whites, to 3,000 demographically matched controls in 
        order to identify differences in risk factor distribution and 
        ICH outcome by race, ethnicity and location of ICH and to 
        determine differences in imaging characteristics among African 
        Americans and Hispanics compared to whites. The investigators 
        will also collect DNA in order to combine with other cohorts to 
        perform a genome-wide association study (GWAS) to identify 
        genes that affect risk of ICH in whites, African Americans and 
        Hispanics.
  --The Alaska Native Stroke Registry (ANSR) is a population-based 
        surveillance study on the epidemiology of stroke in Alaska 
        Natives. Comprehensive assessment of the stroke epidemiology, 
        vascular risk factors, cultural understandings of vascular 
        health and lifestyle, and structural barriers to risk reduction 
        strategies has informed the development of a community level 
        prevention intervention pilot program that aims to reduce the 
        burden of stroke in the Alaska Native population.
                                 ______
                                 
                Questions Submitted by Senator Herb Kohl

    COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENTS TRIALS

    Question. The National Institutes of Health (NIH) recently released 
results of the Comparison of Age-Related Macular Degeneration 
Treatments Trials (CATT), which found that Lucentis and off-label 
Avastin are similarly efficacious at treating neovascular age-related 
macular degeneration (wet AMD). Now that the CATT study is released, 
what is the NIH going to do with the results? The taxpayers spent 
millions of dollars on the CATT study to determine the comparative 
effectiveness of the drugs. I believe the trial results ought to be 
actionable.
    Answer. The National Eye Institute (NEI) recognizes its 
responsibility to fund and conduct scientifically valid clinical 
research and to disseminate the study results to the professional 
clinical community and the public.
    We collaborate extensively with ophthalmic organizations to apprise 
their members of CATT results. In particular, outreach to professional 
groups was the most effective and efficient means of reaching the 
clinical ophthalmic community regarding CATT findings. For example, the 
American Academy of Ophthalmology (AAO) has 30,000 member 
ophthalmologists who are the primary eye care professionals that treat 
wet AMD. The NEI worked with AAO to disseminate CATT results through 
the AAO's Website, newsletters, press releases, and its upcoming annual 
meeting. Additionally, the AAO Executive Director has written 
extensively to the membership in support of CATT. We will continue to 
work with AAO as they develop ``preferred practice plans'' for the 
treatment of wet AMD. The Association for Research in Vision and 
Ophthalmology (ARVO) is a 12,500 member eye research organization 
comprised of clinicians and investigators. CATT investigators presented 
their results at ARVO's annual meeting in May 2011. These two 
organizations will continue to provide information and guidance to 
their members about CATT so that the results can inform clinical care 
decisions.
    The NEI is also working to inform the public about the CATT 
findings. The release of the study was accompanied by an extensive 
media outreach campaign. For example, the NEI hosted a news briefing 
for journalists where the NEI Director and CATT investigators presented 
study findings and fielded questions from more than 60 media outlets. 
Supplemental background video footage was made available to broadcast 
outlets. A press release was also distributed widely to media outlets. 
The NEI generated robust media coverage for CATT, coverage that has 
been intense and more widespread than for other recent studies (see 
accompanying table), despite media competition from the royal wedding 
and the death of Osama Bin Laden. As follow-up to the initial media 
coverage, the NEI distributed CATT results to members of the National 
Eye Health Education Program (NEHEP), a partnership of 60 public and 
private organizations dedicated to eye health education. This program 
provides the NEI with direct access to community-based public health 
education efforts, and we are preparing an NEI webpage devoted to CATT 
along with a brochure including public health information about CATT.
    Of note, the May publication of CATT reported on first year 
results. The second year results will be published in the spring of 
2012. At that time, the NEI will repeat its efforts with professional 
organizations and the media to disseminate CATT results.

                                        NEI CLINICAL TRIAL MEDIA COVERAGE
----------------------------------------------------------------------------------------------------------------
                                                                                     Number of      Pick-up of
                           Study name                               Impressions    original news   original news
                                                                  (millions) \1\      stories       stories \2\
----------------------------------------------------------------------------------------------------------------
CATT.--Comparison of AMD Treatment Trials (2011)................             296             157             234
ETROP.--Early Treatment for Retinopathy of Prematurity Study                 257              20             138
 (2010).........................................................
DRCR-DME.--Ranibizumab plus laser therapy for diabetic macular               232              42              29
 edema (2010)...................................................
ACCORD.--Action to Control Cardiovascular Risk in Diabetes Eye                 8               9         ( \3\ )
 Study (2010)...................................................
GWAS-AMD.--Genome-wide association study genes associated with                16              13               6
 AMD (2010).....................................................
LALES.--Los Angeles Latino Eye Study (2010).....................               3               7         ( \3\ )
Myopia.--Increased pevalence of myopia in United States (2009)..             158              76         ( \3\ )
SCORE.--Standard Care vs. Corticosteroid for Retinal Vein                    150              27              79
 Occlusion (2009)...............................................
LCA.--Leber Congenital Amaurosis (2009).........................             155              32              37
CITT.--Convergence Insufficiency Treatment Trial (2008).........              44             117             183
CDS.--Cornea Donor Study (2008).................................              63             118              74
AREDS2.--Age Related Eye Disease Study 2 (2006).................              17              92         ( \3\ )
----------------------------------------------------------------------------------------------------------------
\1\ Impressions.--Number of people exposed to the news story in print, online, or on television based on
  expected readership or viewers.
\2\ Pick-up.--When an original story is reprinted in another outlet (i.e., an Associated Press article is
  printed in The Washington Post), it is counted as a pick-up.
\3\ Not applicable.

    Question. How does the NIH share this information with other 
agencies within the Federal Government?
    Answer. In the preparation for the release of CATT, the NEI held a 
teleconference with relevant Department of Health and Human Services 
(HHS) agencies (FDA, CMS, CDC, and AHRQ) to inform them of CATT results 
and to coordinate the HHS response to media. In accordance with 
standard HHS and NIH operating procedures, the NEI distributed a draft 
press release for clearance within DHHS and responded to various issues 
prior to approval for release. This effort helped ensure a coordinated 
HHS response to CATT. Since this initial interaction, both the NEI 
staff and CATT leadership have been contacted by CMS staff to discuss 
the implications of the CATT study results.
    Question. Has the NIH's National Eye Institute considered what 
effect, if any, the CATT study might have on future physician 
prescribing behavior regarding Lucentis vs. off-label Avastin to treat 
wet AMD?
    Answer. Avastin, which inhibits the formation of new blood vessels, 
was approved by the FDA in 2004 for the treatment of colon cancer. 
Avastin is effective as an anti-cancer agent because inhibiting the 
blood supply to tumors inhibits their growth. Since wet AMD is due to 
leakage from new, abnormal blood vessels, ophthalmologists began trying 
Avastin off-label to treat this form of AMD in 2006 on the basis of 
both the cancer data and clinical trial results for Lucentis during the 
FDA approval process. At that time, Avastin off-label was the only 
available treatment for wet AMD that led to improvement in vision.
    The vast majority of patients treated for wet AMD participate in 
Medicare. After Lucentis was FDA-approved in 2007, most 
ophthalmologists continued to use Avastin because the cost was 
significantly lower than for Lucentis and because a number of reported 
cases demonstrated Avastin efficacy that appeared similar to that 
reported in the Lucentis clinical trials. Last May, Dr. Ross Brechner 
and colleagues (Centers for Medicare and Medicaid Services) and Dr. 
Phillip Rosenfeld (Bascom Palmer Eye Institute, University of Miami) 
published an analysis of Medicare claims for wet AMD during 2008.\1\ 
They found that 64.4 percent of patients received Avastin and 35.6 
percent received Lucentis and concluded that despite its off-label 
designation, intravitreal Avastin is currently standard-of-care 
treatment for wet AMD. Medicare payments totaled $536.6 million for 
Lucentis and $20.3 million for Avastin.
---------------------------------------------------------------------------
    \1\ Brechner, R. J, P. J. Rosenfeld, J. D. Babish, and S. Caplan. 
Pharmacotherapy for Neovascular Age-Related Macular Degeneration: An 
Analysis of the 100 percent Medicare Fee-For-Service Part B Claims 
File. American Journal Ophthalmology 151:887-895, 2011.
---------------------------------------------------------------------------
    CATT was a very tightly controlled, well-designed study, which 
compared the two drugs in more than 1,100 patients. The exceptionally 
wide dissemination of CATT results means that the retinal specialists 
who treat AMD and the patients they care for are undoubtedly well aware 
of the equivalence. As such, an increase in the number of patients 
receiving Avastin as first line therapy is to be expected. Careful 
monitoring of use of the drugs by CMS is expected.
    Importantly, some patients with wet AMD respond better to Avastin, 
while others to Lucentis. In practice, if one is ineffective, the other 
may be tried. The fact that more than one drug is available is 
beneficial and allows ophthalmologists and patients treatment choices.
                                 ______
                                 
            Questions Submitted by Senator Mary L. Landrieu

                     INTERIM STATUS OF IDEA PROGRAM

    Question. Scientists have expressed their concern about programs 
that have been placed before under ``interim'' status and tend to lose 
direction and in some cases have disappeared. I am particularly 
concerned about the Institutional Development Award (IDeA) Program, 
which is so important to Louisiana. What is the reason for placing a 
program that serves 23 States and Puerto Rico on an interim status?
    Answer. The IDeA Program has not been placed in an interim status. 
Under the proposed creation of the National Center for Advancing 
Translational Sciences (NCATS), we considered moving the program to a 
new unit called the Office of Research Infrastructure Programs within 
the Office of the Director, Division of Program Coordination, Planning, 
and Strategic Initiatives. However, following extensive consultation 
and feedback from multiple stakeholders, including grantees, 
professional organizations, and the public, we concluded that the IDeA 
program is most closely aligned scientifically and programmatically 
with the mission and goals of the National Institute of General Medical 
Sciences (NIGMS). Therefore, the National Institutes of Health (NIH) 
intends on moving the IDeA program and the IDeA program staff to the 
NIGMS. We are confident the program will flourish as a vital component 
of the NIGMS.

  PLACEMENT OF NATIONAL CENTER FOR RESEARCH RESOURCES (NCRR) PROGRAMS

    Question. For many years the programs housed at the NCRR have 
worked synergistically to serve the IDeA community. Can this synergy 
continue by placing these programs under a single NIH institute?
    Answer. There is no reason why synergies established between IDeA 
and other NCRR programs will not continue to flourish at both the 
national level through programmatic communication and collaboration 
across institutes and centers and at the local level through 
institutional collaborations and interactions. Fostering collaborative 
research networks is an inherent part of the IDeA mission, and it 
excels at establishing connections and linkages. IDeA institutions 
currently collaborate with grantees of the Research Centers in Minority 
Institutions (RCMI) program as well as the Science Education 
Partnership Award Program (SEPA). The NIH encourages such 
collaborations, and they will continue.

  PLACEMENT OF IDEA WITHIN THE NATIONAL INSTITUTE OF MINORITY HEALTH 
                          DISPARITIES (NIMHD)

    Question. It has been made public that some institute directors who 
have been approached to house IDeA programs have voiced reservations 
about housing these programs in their institutes based on their 
programmatic mission and staffing needs. We also know that the Advisory 
Council for the NIMHD has enthusiastically endorsed the idea of placing 
these programs in the NIMHD. Have you considered the possibility of 
placing these programs under the management of the NIMHD?
    Answer. An NIH National Center for Research Resources (NCRR) Task 
Force, charged with identifying the optimal new home for the IDeA 
program, considered a range of options, including its placement within 
the NIMHD. After careful analysis, fact-finding, and consultation, the 
Task Force recommended that this program be transferred to the National 
Institute of General Medical Sciences (NIGMS). The IDeA program fosters 
health-related research and enhances competitiveness of investigators 
at institutions located in States in which the aggregate success rate 
for applications to the NIH has been historically low. By its nature, 
the program extends beyond traditional capacity building in supporting 
research projects that are designed to strengthen future investigator-
initiated research applications, most of which are focused on 
addressing basic science questions. The NIGMS has a basic science focus 
as well as a longstanding focus on institutional capacity building and 
career development. Given these synergies, the Task Force determined 
that the mission of the IDeA program is most closely aligned with the 
mission of the NIGMS and that the NIGMS would be the optimal new home 
for the IDeA Program.

THE CLINICAL AND TRANSLATIONAL SCIENCE AWARDS (CTSAS) AND THE NATIONAL 
          CENTER FOR ADVANCING TRANSLATIONAL SCIENCES (NCATS)

    Question. With the final five CTSAs expected to be announced in the 
near future, I have a couple of questions for Dr. Collins on this 
program's future direction now that it is being moved to the new NCATS.
    Because the NCATS is primarily focused on drug development, what 
will become of the community research and integration aspect of the 
CTSAs' mission? Will community involvement continue to be a central 
focus of this program?
    The CTSAs represent translational research across the country, but 
there are no centers in the gulf south--an area with significant health 
needs that would benefit greatly from a CTSA and could contribute much 
to the network of centers. Is geographic distribution considered as 
CTSA sites are being selected?
    Answer. The mission of the NCATS will be to catalyze the 
development of innovative methods and technologies that will enhance 
the development, testing, and implementation of diagnostics and 
therapeutics across a wide range of human diseases and conditions. In 
addition to strengthening and streamlining the therapeutics development 
process, the NCATS will support research aimed at accelerating the 
development, testing, and implementation of products and techniques, 
including diagnostics, drugs, biologics, medical devices, and 
behavioral interventions, for the diagnosis, treatment, and prevention 
of disease. The CTSAs possess the requisite expertise across the full 
spectrum of translational research, and they will be integral to the 
success of the NCATS. The involvement of research sites across the 
Nation and the study of the integration of research findings at the 
community level will continue to be an important focus of the CTSA 
program.
    Institutions with CTSAs that are either close to or interact with 
communities and populations along the Gulf include the University of 
Texas Medical Branch in Galveston and the University of Alabama in 
Birmingham. The CTSA at the University of Texas Health Sciences Center 
at Houston serves gulf communities through its strong connections to 
UT's Brownsville campus.
    With regard to the selection of the CTSA sites, NCRR has used the 
peer review process to establish priority scores to guide funding 
decisions. All applications, together with their priority scores, were 
then reviewed by the National Advisory Research Resources Council, 
which is able to make recommendations, where needed, concerning 
geographic distribution. Going forward, scientific merit will continue 
to be the principal selection criterion, and considerations of program 
relevance and public health need will be factored in at subsequent 
levels of review.

 GEOGRAPHIC DISTRIBUTION OF SMALL BUSINESS INNOVATIVE RESEARCH (SBIR) 
                                 GRANTS

    Question. As one of the largest funders of SBIR grants, can you 
tell me what the NIH is doing to ensure that there is a more balanced 
portfolio and increased participation from States that have 
traditionally received a small number of SBIR grants?
    Answer. The NIH prioritizes SBIR and Small Business Technology 
Transfer (STTR) outreach to States that historically have submitted a 
small number of SBIR applications and/or have lower success rates than 
the overall SBIR/STTR success rates. Each year, we hold an annual SBIR/
STTR conference, this year on the NIH's campus in Maryland, but in past 
years in Ohio, Nebraska, Nevada, Georgia, and North Carolina. We also 
participate in direct one-on-one contact with current and potential 
applicants/grantees in several national, State, and regional SBIR 
events per year. Currently in fiscal year 2011, the NIH staff have 
already attended, presented, or participated on the SBIR program in 
Arizona, California, Florida, Kansas (via webinar), Kentucky, Maine, 
Maryland, Michigan, Missouri, Nebraska, New York, Virginia, Washington, 
DC, and Wisconsin. On the horizon is an event in Louisiana. These 
conferences attract attendees from across the country, and offers 
attendees an opportunity for one-on-one consultations with the NIH 
SBIR/STTR program, review and grants management staff. In addition, 
there are a number of other conferences/meetings in which the NIH 
offers consultation to SBIR/STTR applicants and similar outreach is 
conducted by the individual NIH Institutes and Centers. In all venues, 
the NIH educates as many current and potential applicants/grantees as 
possible about the SBIR program.
    In addition to these in-person opportunities, the NIH staff are 
available to provide assistance to all applicants from concept 
development through grant life-cycle by phone, email, webinars, and our 
Web sites. SBIR funding decisions ultimately are made at the NIH 
Institute level and are based on scientific merit (as determined by our 
two level peer-review system), available funding, and programmatic 
priority. Information about all NIH grant awards, including State 
location, can be accessed through our RePORTER Web site at http://
projectreporter.nih.gov/reporter.cfm.

                     ANTIVIRAL DEVELOPMENT FOR FLU

    Question. Discussions regarding the prevention of a flu pandemic 
frequently focus on vaccine development, but it is my understanding 
that effective management of influenza will require the continued 
development of new antiviral drugs. I was pleased to learn that the 
National Institute of Allergy and Infectious Diseases (NIAID) recently 
held a workshop on the influenza antiviral research pipeline. Are we 
making progress in the development of antiviral drugs for influenza and 
does the NIAID have plans for any new initiatives in this area?
    Answer. In March 2011, the NIAID held the Influenza Antiviral 
Research Pipeline Workshop, which brought together stakeholders from a 
variety of sectors including academia, business, and government. 
Discussions focused on the state of influenza antiviral research and 
spanned all aspects from discovery to advanced clinical development. 
Workshop proceedings will be posted on the NIAID Web site in the near 
future.
    Currently, there are four drugs licensed to treat influenza: 
oseltamivir (Tamiflu), zanamivir (Relenza), rimantadine (Flumadine), 
and amantadine (Symmetrel). Ongoing NIAID efforts in influenza drug 
development include combination studies with licensed and experimental 
drugs, studies of the safety of antiviral drugs in infants and 
children, studies of broad-spectrum antivirals, studies of antibody 
therapeutics, and evaluation of novel drug targets. For example, the 
NIAID also supports in vitro and in vivo antiviral screening and other 
preclinical services to identify new antiviral candidates. In fiscal 
year 2010, more than 100,000 compounds were evaluated by high-
throughput screening assays against multiple influenza A strains, and 
several hundred compounds were tested for their efficacy against 
influenza in animal models. Also, the NIAID is supporting the 
preclinical and clinical development of a novel antiviral drug 
candidate; a safety study has been completed and a Phase II clinical 
trial is ongoing.
    To meet the need for effective influenza management strategies, the 
NIAID will continue to support a robust influenza antiviral research 
portfolio, including discovery of drug targets, identification of 
compounds with novel mechanisms of action, and clinical studies to 
evaluate promising drug candidates.

                            STROKE IN WOMEN

    Question. My State of Louisiana lays in the Stroke Belt, a group of 
Southeastern States where stroke death rates are the highest in our 
Nation. I am concerned about the seriousness of stroke, particularly 
among women who account for 61 percent of stroke fatalities. Please 
tell this subcommittee what studies the NIH is conducting to combat 
stroke in women, including prevention and rehabilitation efforts. In 
addition, please highlight planned activities in these areas.
    Answer. The National Institute of Neurological Disorders and Stroke 
(NINDS) supports a large and broad portfolio of stroke research that 
includes numerous efforts to better understand and address the 
substantial burden that stroke places on women.
    The NINDS supports multiple research studies on the physiological 
basis for gender-related differences in stroke risk and outcomes. One 
study funded by the NINDS and the National Heart, Lung, and Blood 
Institute (NHLBI) will follow a cohort of women to identify biological 
and physiological markers associated with ischemic stroke, and to 
establish which of those are influenced by sex hormones or menopausal 
status. This study will inform future development of gender-specific 
predictors for stroke risk. In another study, investigators will 
explore how biological functions programmed by sex-specific chromosomes 
are related to gender differences observed in cell death pathways 
activated by a stroke. The NINDS also funds a study to investigate the 
role of estrogen receptors in gender-related differences in incidence 
of stroke associated with cardiovascular surgical procedures.
    The NINDS supports a number of surveillance studies that aim to 
illuminate differences in stroke knowledge, risk and outcomes among 
different sub-populations, including women, in order to inform 
development of tailored prevention intervention strategies. For 
example, the Reasons for Geographical and Racial Differences in Stroke 
Study (REGARDS) is a large cohort of more than 30,000 participants, 
more than half of whom are women. This comprehensive assessment of 
disparities in stroke risk and incidence is one of the largest 
longitudinal cohort studies of African Americans and the only national 
study of the epidemiology of cognitive change. The large representation 
of women in this important population-based study is significant as it 
allows for data analyses of gender-specific differences, as well as 
among different racial populations. For example, a recent publication 
from this study revealed that markers for inflammation led to more 
accurate vascular disease risk stratification, particularly in blacks 
and women, since they are at higher risk for increased levels of this 
marker. Studies from REGARDS will continue to improve our understanding 
of differences in stroke risk among a diverse U.S. population.
    The NINDS supports a large number of clinical studies to improve 
acute management and long-term outcomes in stroke. All of the NIH-
funded clinical trials are required to set and justify target 
enrollment by race, ethnicity, and gender and to report on enrollment 
progress. Approximately half of the participants in all of the NINDS-
supported stroke clinical trials are women so that data can be analyzed 
for gender-specific differences. These trials are investigating new 
approaches to treat acute stroke and brain hemorrhage, to reduce brain 
damage due to stroke and to improve rehabilitation strategies, which 
will provide all patients, including women, and their physicians with 
more therapy options and a better chance of survival and recovery after 
a stroke.
    The NINDS is embarking on a new stroke planning effort in 2011 to 
update research progress and activities in response to prior research 
recommendations, and to identify a specific set of high priority areas 
for advancing stroke research over the next 5-10 years. The planning 
effort will specifically address stroke prevention, treatment, and 
recovery in subpopulations, with a special emphasis on women and gender 
differences. Recommendations from this planning effort will inform 
future NINDS research investment and activities related to stroke in 
women.

                             NCI PRIORITIES

    Question. Dr. Varmus, you have stated a desire for the NCI to 
continue to fund as many grants as in previous years, even if this 
means cuts in other areas, such as the Cancer Center program. Could you 
tell us a bit more about your plans and priorities for the institute 
and possible changes on the horizon?
    Answer. Cancer is a complex disease requiring many approaches to 
make progress. It is important to fund as many meritorious grants as we 
possibly can within the resources we are given, because individual 
grants allow us to pursue new ideas effectively. We will be finding 
savings across the Institute by taking money away from routine 
administrative expenses, making cuts to the intramural and Cancer 
Centers programs, and by conducting reviews of large programs and 
cutting where possible. This will allow us to achieve acceptable grant 
levels and to protect certain imperatives.
    In addition, realignment of the clinical trial cooperative groups, 
as recommended by the Institute of Medicine report in 2010, will 
improve the efficiency of the overall system and enable the cooperative 
groups to conduct state of the art oncology research more consistently. 
Funding for this effort is a priority for the NCI. A second imperative 
is maintaining the pace of work on cancer genomics. The Cancer Genome 
Atlas (TCGA), a project undertaken by the National Cancer Institute and 
the National Human Genome Research Institute to gain an understanding 
of the molecular basis of cancer, has already produced results in brain 
cancer and ovarian cancer. The rate of discovery is dependent on the 
level of funding. Therefore, we place a high priority on protecting 
funding for this project and other meritorious efforts in cancer 
genomics. As TCGA is expanded to include many cancer types, the 
ultimate goal is to ensure that genetic information is applied to 
prevention, diagnosis, and treatment of cancer in clinical practice.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin

                ECONOMIC BENEFITS OF BIOMEDICAL RESEARCH

    Question. According to a recent Families USA report, every $1 
investment in medical research stimulates $2.43 in business activity--
such as support staff, supplies, food services, and building 
development. Are you aware of other studies that attempt to quantify 
the local impact of the Federal investment in medical research? Are 
there any efforts underway at the NIH to capture the return-on-
investment that taxpayers receive as a result of the Federal commitment 
to research?
    Answer. To the best of our knowledge, there are two comprehensive 
published studies that attempt a quantification of the economic effects 
of the NIH spending at the State level, both supported by research 
advocacy groups. Both studies rely on the Regional Input-Output 
Modeling System (RIMS II), developed by the Bureau of Economic Analysis 
at the Department of Commerce. RIMS II measures, at a State level, the 
economic multiplier effect generated by local demand. National 
aggregate averages are extrapolated from State data.
    The first report was released in June 2008 by Families USA and was 
titled ``In your own backyard.'' \1\ The report found, among other 
things, that in fiscal year 2007, the NIH funding supported more than 
350,000 jobs that generated wages in excess of $18 billion in the 50 
States. The average wage for these jobs was $52,000. It also found that 
$1 spent by the NIH funding generates $2.21 of business activity at the 
State level. This $2.21 figure is an average; individual States may 
vary (e.g., in Illinois, the figure is $2.43.)
---------------------------------------------------------------------------
    \1\ FamiliesUSA. (2008). In Your Own Backyard: How NIH Funding 
Helps Your State's Economy. Washington, DC. Retrieved December, 2008 
from http://www.familiesusa.org/issues/global-health/publications/in-
your-own-backyard.html.
---------------------------------------------------------------------------
    More recently, in May 2011, the organization ``United for Medical 
Research'' released a report, titled: ``An Economic Engine. NIH 
Research, Employment and the Future of the Medical Innovation Sector.'' 
\2\ The report draws three conclusions: the NIH extramural research is 
an important source of income and employment around the country; the 
complementary relationship between public NIH investment and private 
industry development is critical to the health and well-being of our 
Nation; and the U.S. medical innovation sector is facing increasing 
challenges in maintaining America's competitiveness and position as the 
world leader in medical research. The report found that in fiscal year 
2010, the NIH directly and indirectly supported nearly 488,000 jobs and 
produced $68 billion in new economic activity and that $1 of the NIH 
investments generated, on average, $2.60 of business activity, at the 
national level.
---------------------------------------------------------------------------
    \2\ Ehrlich, E. (2011). United for Medical Research from http://
www.unitedformedicalresearch.com/wp-content/uploads/2011/05/
UMR_Economic-Engine.pdf.
---------------------------------------------------------------------------
    The NIH has worked closely with experts in the field of labor and 
health economics and R&D evaluation on several projects. One of the 
studies found that a one dollar increase in the NIH funding leverages 
an additional 35 cents in funding from non-Federal sources.\3\
---------------------------------------------------------------------------
    \3\ Blume-Kohut, M., Kumar, K. B., & Sood, N. (2008). The Impact of 
Federal Funding on University R&D. Retrieved November 7, 2009 from 
http://www.rand.org/labor/seminars/brown_bag/pdfs/2008_sood.pdf
---------------------------------------------------------------------------
    Another study determined that 33 percent of all drugs approved by 
FDA and 58 percent of approved priority review new molecular entities 
(which tend to be the most innovative drugs) cite an NIH-funded 
publication or an NIH patent.\4\
---------------------------------------------------------------------------
    \4\ Lichtenberg, F. R., & Sampat, B. (2011). What are the 
respective roles of the public and private sectors in pharmaceutical 
innovation? Health Affairs, 30(2), 332-338.
---------------------------------------------------------------------------
    Another study showed that multinational companies in the 
pharmaceutical sector tend to locate their R&D facilities next to hubs 
of skilled workers. This finding underscores the importance of the NIH 
investments in sustaining a strong research infrastructure system in 
the United States and avoiding the loss of private sector investments 
in R&D that could be moved abroad.\5\
---------------------------------------------------------------------------
    \5\ Thursby, J. G., & Thursby, M. C. (2009). Is the US a Target of 
R&D Globalization? Location, Type and Purpose of Biomedical Industry 
R&D in New Locations: NBER. Report prepared for the NIH Office of 
Science Policy Analysis.
---------------------------------------------------------------------------
    Another study, Economic Impact of the Human Genome Project (http://
www.battelle.org/publications/humangenomeproject.pdf), which was 
commissioned by the Life Technologies Foundation and prepared by the 
Battelle Technology Practice Foundation, assessed the benefits of the 
Federal investment of the Human Genome Project (HGP). Finding that the 
benefits are widespread and increasing over time, the report cites 
among other factors, the production of 3.8 million job-years of 
employment (one job-year for each $1,000 invested) and the generation 
of personal income (wages and benefits) exceeding $244 billion over the 
last 7 years, an average of $63,700 per job-year.
    With regard to whether there are other efforts underway at the NIH 
to capture the return-on-investment that taxpayers receive as a result 
of the Federal commitment to research, the NIH is also participating in 
the STAR METRICS Project.\6\ \7\ STAR METRICS is a collaboration 
between Federal science agencies and research institutions to document 
how Federal science investments support knowledge creation, economic 
growth, workforce development and a broad range of societal outcomes. 
The program's goal is to build a data infrastructure that will bring 
together inputs, outputs, and outcomes from a variety of sources in as 
open a fashion as possible.
---------------------------------------------------------------------------
    \6\ https://www.starmetrics.nih.gov/.
    \7\ Lane, J., & Bertuzzi, S. (2011). Research funding. Measuring 
the results of science investments. Science, 331(6018), 678-680.
---------------------------------------------------------------------------
    STAR METRICS has two levels and the NIH participates in both. Level 
I documents the initial effect of S&T investments on employment using 
administrative records from research institutions. This approach goes 
beyond the RIMSII model, capturing the actual, rather than estimated, 
number of jobs supported. Level II builds on Level I by connecting 
sources of funding, recipients of funding, interactions among 
scientists (in both the public and private sector) and the products of 
research over time ranging from the most proximal (such as meeting 
presentations and publications) to more distal (such as the development 
of a new drug).

                     CONGENITAL HEART DISEASE (CHD)

    Question. Congenital Heart Disease (CHD) is one of the most 
prevalent birth defects in the United States and a leading cause of 
birth defect-associated infant mortality. Due to medical advancements 
more individuals with congenital heart defects are living into 
adulthood. Please provide an update of research within the NIH, 
particularly the National Heart, Lung, and Blood Institute (NHLBI) 
related to congenital heart defects across the life-span. The 
healthcare reform law included a provision, which I authored, that 
authorizes the CDC to track the epidemiology of congenital heart 
disease, with an emphasis on adults with CHD and expanding 
surveillance. If adequately funded, how could a population-surveillance 
system for adults with CHD support the NIH's ability to investigate CHD 
across the life-course and across subgroups?
    Answer. The NIH supports research on CHD across the lifespan. For 
example, as part of its Pediatric Heart Network, the NHLBI is following 
participants in an earlier study of the Fontan surgical procedure to 
assess functional health status, neurocognitive performance, and 
transitions from pediatric care to adult care for CHD. Through its 
Bench-to-Bassinet program, the NHLBI is examining the genetic causes of 
CHD and the effects of genetic variation on the long-term clinical 
outcomes of affected children as they grow older. The NHLBI also funds 
a research partnership between the Adult Congenital Heart Association 
and the Alliance of Adult Research in Congenital Cardiology that seeks 
to improve care delivery and long-term outcomes for adults with CHD and 
also to inform research designs for studies in adults. Through its 
Pumps for Kids, Infants, and Neonates (PumpKIN) program the NHLBI 
supports development of pediatric devices for congenital heart disease. 
In addition, an investigator-initiated project seeks to develop a blood 
pump for patients who have undergone the Fontan surgery. Patients who 
have had the surgery experience significant morbidity due to diminished 
blood flow, especially as they grow into adulthood, and a device to 
assist blood flow could dramatically improve care.
    An adequately funded population-surveillance system for adults with 
CHD could facilitate the NIH research. The surveillance data would help 
the NIH ensure that its research efforts address the full range of 
heart conditions, risk factors, and complications across the lifespan; 
provide the potential to link genetic and other biological information; 
permit monitoring of the effectiveness of new preventive and 
therapeutic strategies; and identify a potential pool of patients who 
could benefit from participation in various research activities. 
However, funding was not provided for this provision in the Affordable 
Care Act, and no funds have been requested within the budget for the 
Centers for Disease Control and Prevention to implement it.

                        THE CANCER GENOME ATLAS

    Question. The National Cancer Institute is making tremendous 
progress with the Cancer Genome Atlas (TCGA) in sequencing cancer 
genomes and then using scientific discoveries to further specific 
fields of cancer research. What is the status of the TCGA gastric 
cancer project? Specifically, the pilot project to utilize contiguous 
biopsies to sequence the genome for the diffuse gastric cancer subtype? 
How will the NCI utilize these groundbreaking discoveries to further 
the field of gastric cancer research? What other initiatives and steps 
is the NCI taking to investigate gastric cancer?
    Answer. TCGA staff and extramural researchers have been steadily 
working on identifying, collecting, and assessing the quality of 
gastric cancer biospecimens for inclusion into TCGA's genotyping and 
molecular characterization pipeline. However, due to the difficulty in 
obtaining qualifying biospecimens from patients with diffuse gastric 
cancer, the NCI began to explore a pilot project for collection of 
diffuse gastric cancer biospecimens. The challenges involved in this 
pilot project of multiple gastric biopsies was discussed in detail in 
May 2011 when the NCI hosted a workshop on gastric and esophageal 
cancer, bringing together a group of international experts to explore 
and discuss the basic biology, epidemiology, and clinical research 
aspects of these cancers across the world. There was tremendous 
interest in the pilot study from the gastric cancer researchers, and in 
June 2011 the NCI approved TCGA to proceed with the pilot study to 
collect biospecimens on a small number of diffuse gastric cancers from 
the United States. The extent of the project will depend on the cost 
per case and the number of centers willing to participate. We are 
hopeful that analysis of these biospecimens will yield valuable 
information that will stimulate novel research approaches for this 
challenging disease and will lead to advances in the prevention, 
diagnosis, and treatment of diffuse gastric cancer.
    In addition to the TCGA-related efforts, an NCI Genome-Wide 
Association Study (GWAS) on gastric adenocarcinoma and esophageal 
squamous cell carcinoma has already revealed a common cancer 
susceptibility region at PLCE1, and the NCI is funding follow-up 
mechanistic studies on the effect of the gene variations in this 
location. A second GWAS will be conducted in a mostly Caucasian cohort 
to provide further clues about susceptibility regions and whether they 
differ between populations that experience different rates of gastric 
cancer. The NCI also funds broad based research at four 
Gastrointestinal Cancer Specialized Programs of Research Excellence 
(SPOREs), two of which include a focus on esophageal cancers.

               EOSINOPHILIC-ASSOCIATED DISORDERS RESEARCH

    Question. Eosinophilic-associated disorders were identified in the 
last decade. Consequently many people go undiagnosed for years, due to 
lack of information and awareness about these diseases. Please describe 
current efforts at the NIH, particularly the National Institute for 
Allergy and Infectious Diseases (NIAID) to investigate eosinophilic-
associated disorders. Last year, the Senate budget included report 
language urging the NIAID to convene a working group to develop a 
research agenda aimed at improving the diagnosis and treatment of 
eosinophilic-associated disorders. What strides are the NIH and the 
NIAID making to develop a research agenda focused on these conditions?
    Answer. As the lead institute at the NIH responsible for research 
on immunologic and allergic disorders, the NIAID is committed to 
research to better understand the mechanisms that mediate tissue injury 
when eosinophils accumulate, including eosinophilic gastrointestinal 
disorders, a group of recently recognized allergic diseases associated 
with the production of IgE antibodies and other immune responses to 
food. The NIAID works closely with other NIH Institutes and Centers 
supporting research on eosinophilic disorders. Although these 
collaborations and communications do not occur through a formal working 
group or a predetermined research agenda, they have led to jointly 
sponsored workshops and research initiatives on eosinophilic disorders. 
In fiscal year 2012, the NIH, with the NIAID as the lead, will 
establish a working group with participation by relevant NIH Institutes 
and Centers, to develop a trans-NIH strategy to improve the diagnosis 
and treatment of eosinophilic disorders.
    As part of its overall research agenda on immunologic and allergic 
diseases, the NIAID pursues research on eosinophilic disorders through 
a variety of efforts and collaborations. For example, the Consortium of 
Food Allergy Research (CoFAR), co-funded with the National Institute of 
Diabetes and Digestive and Kidney Diseases (NIDDK), and renewed in 
fiscal year 2010, develops new approaches to treat and prevent food 
allergy. A new CoFAR project is examining the genetic aspects of 
eosinophilic esophagitis. The NIAID Asthma and Allergic Diseases 
Cooperative Research Centers (AADCRC) support basic and clinical 
research on the mechanisms, diagnosis, treatment, and prevention of 
asthma and allergic diseases, including food allergy and anaphylaxis. 
Many of these disorders are associated with eosinophilia. In addition, 
the NIAID-supported investigators are conducting a pilot clinical trial 
to determine the efficacy of swallowed glucocorticoids for the 
treatment of eosinophilic esophagitis, and developing novel noninvasive 
diagnostic tools for eosinophilic gastrointestinal diseases to reduce 
the number of endoscopies and biopsies that are currently performed. 
Also, on behalf of more than 30 professional organizations, Federal 
agencies, and patient advocacy groups, including the American 
Partnership for Eosinophilic Disorders, the NIAID coordinated the 
development of Guidelines for the Diagnosis and Treatment of Food 
Allergy in the United States. This document includes clinical practice 
guidelines for the diagnosis and management of eosinophilic esophagitis 
associated with food allergy. The guidelines were published in the 
December 2010 issue of the Journal of Allergy and Clinical Immunology 
and can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21134576.
    The NIAID will continue its commitment to research and trans-NIH 
research collaborations on eosinophilic disorders to understand the 
mechanisms that mediate tissue injury when eosinophils accumulate. As 
part of this effort, in fiscal year 2011, the NIAID will recompete the 
AADCRC program.
                                 ______
                                 
               Questions Submitted by Senator Mark Pryor

                       EXTRAMURAL RESEARCH BUDGET

    Question. What percentage of the NIH's funding leaves the greater 
Washington, DC area and goes to medical research in States and local 
communities?
    Answer. In fiscal year 2010, the NIH awarded 82 percent ($25.6 
billion of $31.2 billion) of its budget to more than 3,000 institutions 
and organizations across the United States, as well as several other 
countries throughout the world, 71 percent ($22.1 billion) in grants 
and 11 percent ($3.5 billion) in research and development contracts. 
The percentage of the fiscal year 2011 budget devoted to extramural 
research is also expected to be approximately 82 percent. An overview 
of the NIH funding allocations by Institute and Center in fiscal year 
2010, fiscal year 2011, and the fiscal year 2012 budget is available 
at: http://officeofbudget.od.nih.gov/pdfs/FY12/
COPY%20of%20NIH%20BIB%20Chapter%202-9-11-%20FINAL.PDF.

                  PERSONALIZED MEDICINE AS A PRIORITY

    Question. As you well know, we are currently in a very difficult 
economic time. The Congress is in the process of making many decisions 
related to addressing the Nation's budget problems. We are considering 
many ways to control our costs and minimize additional debt, but at the 
same time, we have to prioritize and ensure that important programs are 
adequately funded. Having said that, do you believe advances in 
personalized medicine could be threatened should the Congress enact 
cuts to the NIH's budget?
    Answer. Through the application of genomic research and high-
throughput technologies, breakthroughs in our understanding of the 
causes of many diseases and the identification of new targets and 
pathways for the development of new therapeutics are within reach. For 
example, a decade ago, diagnosis of cancer was based on the organ 
involved and treatment depended on broadly aimed therapies that often 
greatly diminished a patient's quality of life. Today, research in 
cancer biology is moving treatment toward more effective and less toxic 
therapies tailored to the genetic profile of each patient's cancer. The 
NIH research is also identifying genetic markers that can predict 
whether an individual will respond well to a particular medication or 
will be at risk of having an adverse reaction. The NIH-funded 
researchers are also uncovering information about genes and the 
environment that will help point the way toward more personalized, 
targeted treatments for other diseases. The new National Center for 
Advancing Translational Sciences (NCATS) will provide the 
infrastructure and technologies to bring these critical basic 
discoveries to fruition through new diagnostics and therapeutics. 
Significant budget cuts could threaten the NIH's ability to continue to 
support these advances. However, the specific research areas that would 
be affected in the event that budget cuts materialize cannot be 
determined now since the NIH would need to re-evaluate its research 
priorities.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby

                    REORGANIZATION OF NCRR PROGRAMS

    Question. There remain concerns within the Congress and the 
research community with the decision to eliminate the National Center 
for Research Resources (NCRR). Can you explain the rationale behind 
this decision and where the National Center for Research Resources' 
assets will be moved?
    Answer. With the decision to move the Clinical And Translational 
Science Awards (CTSAs) into the proposed National Center for Advancing 
Translational Sciences (NCATS), it was necessary to consider the impact 
of its transfer on NCRR and whether there were long-range benefits that 
could be achieved by relocating its remaining programs within other NIH 
components. A task force was formed to determine if the remaining 
programs should be kept in a separate organization or if there was an 
opportunity for greater scientific synergies by moving the remaining 
programs to other NIH components. The task force was guided by the 
following considerations and principles in developing its 
recommendations:
  --The scientific synergies that could be achieved by placing the NCRR 
        program in adjacency to existing (or in the case of the NCATS, 
        proposed) portfolio/mission of the recipient IC versus the 
        existing synergies among the NCRR programs.
  --The ``goodness of fit'' for the NCRR program within the recipient 
        IC versus the negative effects of adding a program that is 
        disproportionately large and/or not well aligned to the 
        recipient IC's current (or in the case of the NCATS, proposed) 
        mission.
  --The level of disruption to long-standing NCRR programs led by 
        dedicated NCRR staff versus the disruptive innovation from 
        reassigning NCRR staff to enable interactions with new 
        colleagues and/or new programs.
    The Task Force agreed with the SMRB recommendation that the CTSAs 
be placed in the proposed Center. The Task Force then determined that 
the greatest scientific synergies could be achieved by placement of the 
remaining programs to other components of the NIH. The Research Centers 
in Minority Institutions (RCMI) program was proposed for placement in 
the National Institute for Minority Health and Health Disparities; the 
Institutional Development Award (IDeA) program was proposed for 
placement in the National Institute for General Medical Sciences 
(NIGMS); the Imaging and Point-of-Care Biomedical Technology Research 
Center (BTRC) grants, and Biomedical Imaging, and Point-of-Care 
research grants for Technology Research and Development were proposed 
for placement in the National Institute of Biomedical Imaging and 
Bioengineering; the remaining BTRCs and all other research grants for 
Technology Research and Development, and the BIRN network grants were 
proposed for placement in the NIGMS; the Gene Vector Repository was 
proposed for placement in the National Heart, Lung, and Blood 
Institute; and the Comparative Medicine Program, Extramural 
Construction and Animal Facilities Improvement, Shared and High-End 
Instrumentation, and Science Education Partnership Awards (SEPA) were 
proposed for placement in a new Office of Research Infrastructure 
Programs in the Division of Program Coordination, Planning, and 
Strategic Initiatives in the Office of the Director.
    The Task Force implemented a transparent process to collect and 
consider input from a wide range of internal and external experts, as 
well as stakeholders ranging from members of the public to members of 
the extramural research community. As the deliberations progressed, the 
NIH made information available to the public through a feedback page 
available on its website. The final Task Force recommendations were 
accepted by the NIH Director and the Secretary, and transmitted to the 
House and Senate Appropriations Committees in a letter dated June 6, 
2011. Additional budget details on the reorganization were provided to 
the subcommittees on June 23, 2011.

                   BASIC AND APPLIED RESEARCH BALANCE

    Question. How do you balance the NIH's goals in research aimed at 
knowledge generation (basic research) versus translation of that 
knowledge toward cures and improving human health (applied research)? 
Will the NCATS help to achieve a better balance?
    Answer. Basic research advances knowledge of fundamental biological 
processes and elucidates the molecular underpinnings of human health 
and disease. Basic research makes it possible to understand the causes 
of disease onset and progression and opens up new avenues for 
developing new and improved diagnostics, therapeutics, and preventive 
strategies. Realizing the benefits of fundamental biomedical 
discoveries depends on the translation of that knowledge into 
strategies and products that treat disease and sustain and improve 
health. It is important to understand that ``basic'' and 
``translational'' research are inherently interrelated and comprise a 
cyclical process. There are important feedback loops between the fields 
so that advances in one ultimately yield new avenues for scientific 
inquiry and discovery in the other. Breakthroughs in our understanding 
of therapeutic targets and pathways also stimulate new avenues for 
basic scientific inquiry. By studying the process of developing new 
therapeutics and diagnostics in an open access environment, the NCATS 
will ultimately catalyze the cycle of discovery in order to advance 
public health.
    From a funding standpoint, 54 percent of the NIH budget is devoted 
to basic research and 46 percent to applied research, a ratio that has 
not varied appreciably for decades. The NIH does not intend to shift 
resources currently devoted to basic research to fund translational 
research. The NCATS will be formed through the realignment of existing 
translational research programs and, as such, will not affect the 
balance of basic and applied research supported by the NIH. It will 
certainly use discoveries made through basic research to advance its 
work while also providing important insights for basic scientists to 
pursue.

            MOLECULAR LIBRARIES PROGRAM AS PART OF THE NCATS

    Question. Dr. Collins, can you discuss the NIH Roadmap Molecular 
Libraries Probe Production Center Network component of the NCATS. I 
understand that this national network of centers provides for the first 
time a sophisticated infrastructure for drug discovery to the academic 
and nonprofit research community. What role will this program play in 
the NCATS going forward?
    Answer. The NIH Molecular Libraries Probe Production Center Network 
(MLPCN), a component of the NIH Molecular Libraries Program (MLP), is a 
collaborative research network that enables the generation of effective 
and useful small molecule chemical probes for the entire biomedical 
research community. Through support from the NIH Common Fund, the MLPCN 
offers biomedical researchers access to large-scale screening capacity, 
along with medicinal chemistry and informatics needed to convert the 
large number of active compounds identified by high-throughput 
screening into useful probes for studying the functions of genes, 
cells, and biochemical pathways. Traditionally, these resources and 
associated expertise have resided exclusively within the private 
sector.
    By providing early stage chemical compounds to the biomedical 
research community, the NIH anticipates that the components of the MLP 
can further enable researchers in both the public and private sectors 
to validate new drug targets, which could then move into the drug-
development pipeline. This is particularly true for rare diseases, 
which may not be attractive for development by the private sector. For 
this reason, several components of the Common Fund's MLP are 
transitioning to be funded and managed through the NCATS. These include 
the Small Molecule Repository, Cheminformatics/PubChem, and the NIH 
Chemical Genomics Center (NCGC), an intramural high-throughput 
screening Center. The Common Fund will continue to provide support for 
the Chemical Diversity technology development program, the Imaging 
Probe Database, and the extramural Specialized Screening Centers.

              THE NIH, ACADEMIA, AND INDUSTY RELATIONSHIP

    Question. Much of the country's translational research has been 
within the pharmaceutical industry and the biotechnology community. Can 
you elaborate on the relationship between the NCATS and these entities? 
Is there a change in roles in academia and the commercial world?
    Answer. The process of translating fundamental knowledge into new 
or better clinical applications is an exceedingly complex, costly, and 
risk-laden endeavor. Moreover, the average length of time from target 
discovery to FDA approval of a new drug is 14 years and the failure 
rate exceeds 95 percent, i.e., fewer than one out of twenty projects 
that enter the drug development pipeline will result in a new FDA-
approved product. At the same time, recent progress in genomics, 
biotechnology, and other fields of biomedical research has advanced the 
potential for development of new diagnostics and treatments for a wide 
range of diseases, opening a wide door of opportunity in translational 
science.
    There is a growing recognition on the part of all those involved in 
translational medicine that the current model for development is not 
sustainable and that novel partnerships and collaborations are critical 
to progress. The NIH is uniquely positioned to help bring about the 
changes by complementing the translational efforts of each sector. To 
achieve this goal, the NCATS will bring together resources and skilled 
scientists to study the steps in the therapeutics development and 
implementation process, consult with experts in academia and the 
biotechnology and pharmaceutical industries to identify bottlenecks in 
the processes that are amenable to re-engineering, and develop new 
technologies and innovative methods for streamlining the processes. 
Cross-sector collaborations will be an essential part of how the NCATS 
operates.

                          FUTURE OF R01 FUNDS

    Question. Will the establishment of the NCATS result in the loss of 
R01 funds?
    Answer. No. Funds for research project grants will not be affected 
by the establishment of the NCATS, which is being created by realigning 
several existing NIH translational research programs. The NCATS will 
stimulate the pursuit of new avenues of scientific inquiry by 
facilitating and complementing translational research efforts carried 
out elsewhere at the NIH. It will not diminish the agency's commitment 
to basic science. Moreover, the NIH requested an additional $100 
million for the operation of the Cures Acceleration Network within the 
NCATS, some of which would be used for research project grants.

                    PROCESS INNOVATION AND THE NCATS

    Question. Dr. Collins, you have stated that ``process innovation'' 
is an important component of the NCATS. Can you explain what this is 
and why it is important? How will process innovation relate to 
individual disease-focused projects the NCATS may do?
    Answer. Process innovation involves studying the therapeutics 
development process with the goal of developing new approaches and 
technologies that can strengthen and streamline the development 
pipeline itself. By approaching the development pipeline as a 
scientific question, the NCATS will identify bottlenecks in the 
processes that are amenable to re-engineering and develop new 
technologies and innovative methods for improving and advancing the 
discovery, testing, and implementation of new therapeutics. Among the 
specific developmental steps that may be addressed are target 
validation, preclinical toxicology testing, clinical trial design, and 
drug rescue and repurposing. In order to evaluate these innovations and 
new approaches, the NCATS will undertake targeted therapeutics 
development and implementation projects that may have relevance to 
individual disease-focused projects.

           REORGANIZATION OF THE COMPARATIVE MEDICINE PROGRAM

    Question. I have heard from several elite schools of medicine, 
including Stanford, MIT, UAB, and Auburn that splitting the components 
of the National Center for Research Resources' Comparative Medicine 
program into different administrative entities would have a negative 
impact on the NIH's critical scientific infrastructure. Dr. Collins, 
can you address their concerns and share with the subcommittee a 
solution to ensure components of the Comparative Medicine program 
remains intact and together within the new organizational structure?
    Answer. Initially, we had considered a number of options with 
regard to the placement of the programs within the Division of 
Comparative Medicine, including dividing them among relevant institutes 
and centers. However, following extensive consultation with multiple 
stakeholders, including grantees, professional organizations, and the 
public, we concluded that it was important to keep the programs within 
the Division of Comparative Medicine together because of their 
intrinsic uniqueness and synergies. As such, the Division of 
Comparative Medicine is to be transferred in its entirety to the new 
Office of Research Infrastructure Programs in the Division of Program 
Coordination, Planning, and Strategic Initiatives within the Office of 
the Director.

                      BROADENING THE IDEA PROGRAM

    Question. The National Center for Research Resources' Institutional 
Development Award program broadens the geographic distribution of the 
NIH funding for biomedical and behavioral research. It is my 
understanding that the goal of the program is to expand biomedical 
research capabilities to areas that currently lack it through research 
and infrastructure funding opportunities and faculty development.
    In its entirety, Alabama is a significant recipient of the NIH 
funding, mainly due to the research funding received by its two medical 
schools. While they provide great benefit to my State and Nation 
through medical breakthroughs and economic investment, I am concerned 
that their success puts other Alabama institutions at a competitive 
disadvantage with similar institutions in IDeA-eligible States.
    Has the NIH considered ways to include institutions in this program 
from non-IDeA eligible States? If not, are there other avenues within 
the NIH that could serve a similar role to IDeA for schools in States 
where one or two universities' significant NIH funding limits their 
access to preliminary support?
    Answer. The current authorization language for the IDeA program 
limits participation in the program to institutions located in States 
with low aggregate success rates for obtaining NIH funding or States 
that do not attain a particular level of support from the NIH. It does 
not allow for participation by institutions from States with high 
success rates or States that receive substantial support from the NIH. 
In 2008, a working group of NCRR's advisory council, which was formed 
to review the eligibility criteria for the IDeA program, explored 
whether it would be possible to base eligibility on institutional or 
regional success rates. The group was unable to identify an alterative 
approach that met the intent of the law.
    In States that are not eligible for IDeA, institutions with limited 
NIH funding are encouraged to participate in are encouraged to apply 
for Academic Research Enhancement Awards (AREA) http://grants.nih.gov/
grants/funding/area.htm which supports 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 the NIH research grant funds. In addition, 
institutions could try to increase the NIH grant support by partnering 
with institutions with more significant NIH funding. Such partnerships 
can help build the experience and capacity necessary to successfully 
compete independently for the NIH funding in the future.

                 GULF OIL SPILL HEALTH EFFECTS RESEARCH

    Question. According to the NIH press statement, of the 40 known oil 
spills in the past 50 years, the health effects have been studied from 
only eight of those spills. I am pleased to see the NIH will begin to 
review health effects of people impacted by the Deepwater Horizon oil 
spill in the Gulf of Mexico. It is critical to understand how being 
exposed to the oil and the dispersants may have affected the health of 
cleanup workers and volunteers. Could you discuss how this study will 
be conducted and what you are hoping the GULF Study will help us learn?
    Answer. The Gulf Long-term Follow-up Study (GuLF STUDY) will help 
determine if oil spills and exposure to crude oil and dispersants 
affect physical and mental health. The National Institute of 
Environmental Health Sciences (NIEHS) is leading this research. A major 
facet of the study is to compare the health of clean-up workers and 
others who did not do clean-up work to learn if health problems are 
more common in workers. GuLF STUDY researchers will also examine other 
factors that may explain why some people are more likely than others to 
get sick and how stress affects health. The NIEHS will send 
approximately 90,000 invitation letters to people to be included in the 
study. Of this group it is expected that 55,000 will be enrolled and 
complete telephone interviews. Participants will be interviewed about 
their oil-spill clean-up jobs, demographic and socioeconomic factors, 
occupation and health histories, and current health, including stress 
and mental health. About half of the cohort will be asked to complete a 
brief clinical examination in their home. The home exam will include 
additional health questionnaires and collection of biological samples, 
such as blood and urine, and environmental samples, e.g., house dust. 
The exam will include basic clinical measurements such as height, 
weight, blood pressure and tests of lung function. The home exams will 
largely target workers residing in the four most affected Gulf States--
Louisiana, Mississippi, Alabama, and Florida). All cohort members will 
be followed for development of a range of health outcomes. Follow-up of 
the entire cohort is initially planned for 10 years, with extended 
follow-up possible depending upon scientific and public health needs 
and the availability of funds.
    GuLF STUDY researchers are hoping to learn if exposure to 
constituents of oil, dispersants, and oil-dispersant mixtures during 
oil spill clean-up is associated with adverse health effects, 
particularly respiratory, neurological, hematologic, and mental health. 
In addition, this research is anticipated to reveal biomarkers of 
potentially adverse biologic effects associated with oil spill-related 
exposures. Results of the study will provide further insight into how 
stress and job loss can affect health, including mental health. 
Overall, the findings may influence long-term public health responses 
in Gulf communities or responses to other oil spills in the future.

                        CYSTIC FIBROSIS RESEARCH

    Question. In February, the NIH announced that federally funded 
research led to the development of a very promising therapy that 
targets the genetic defect that causes Cystic Fibrosis. How will the 
fiscal year 2012 NIH budget request support additional research on 
Cystic Fibrosis?
    Answer. Cystic fibrosis (CF) research continues to be a high-
priority area. The NIH estimates the fiscal year 2012 budget request 
would support about $88 million for CF research, ranging from basic 
science studies through clinical trials. The results of our prior 
investments have provided enormous benefit to affected patients. 
Whereas years of life expectancy for children born with CF could once 
be counted on the fingers of one hand, today average survival is 37 
years and some patients live into their 50s and beyond. Evidence-based 
improvements in nutrition, infection control, and symptom management 
have substantially enhanced the quality of life of affected persons. 
Newborn screening for cystic fibrosis, now universal in the United 
States, is not only enabling early interventions but also providing 
unprecedented opportunities for effective translation of new research 
advances into clinical practice.
    With improved understanding of CF biology, advances in experimental 
methods, and growing availability of new targets for interventions, we 
anticipate that CF research will be especially productive in the next 
few years and that tangible improvement in patient outcomes will 
follow. The recent NHLBI workshop ``Future Research Directions in the 
Pathogenesis, Treatment, and Prevention of Early Cystic Fibrosis Lung 
Disease'' identified a number of important topics for future research 
that can be pursued as funding permits. They include work with animal 
models to understand how early lung disease develops, identification of 
genetic and environmental factors that modify the manifestations and 
course of CF, examination of the role of mutant CFTR (the defective 
gene product in CF) in airway growth and development, and exploration 
of the mechanisms that underlie CF-related diabetes and liver disease. 
The NIH will continue to adjust its research portfolio in CF to ensure 
that needs and opportunities for advancing research are addressed.

                       THE NIH-FDA COLLABORATIONS

    Question. The development of treatments for diseases, especially 
rare diseases, is an expensive and lengthy process. A very small 
percentage of potential medicines even make it to the clinical research 
stage, let alone to FDA review. What can the NIH do to reduce some of 
the regulatory requirements that both slow the pace and increase the 
cost of medical research, but that add little meaningful 
accountability?
    Answer. The NIH is taking a multi-pronged approach to promote 
efforts to address unnecessary, inconsistent, and duplicative 
regulatory requirements. We work closely with FDA and the Office for 
Human Research Protections to enhance the consistency of regulations 
governing clinical research. Through the NIH-FDA Joint Leadership 
Council, we are working with FDA to help ensure that regulatory 
considerations are a component of scientific research at all phases of 
development and they are informed by the most current science and 
technologies. Such efficiencies along with targeted support for the 
development of novel technologies including new and improved 
preclinical toxicology approaches for testing safety should quicken the 
pace and reduce the human-related costs of medical research. The 
proposed National Center for Advancing Translational Sciences will be 
focused on studying diagnostics and therapeutics development, testing, 
and implementation; identifying bottlenecks amenable to re-engineering; 
and formulating innovative methods to streamline the process.

                         CLINICAL TRIAL PROCESS

    Question. One of the priorities of the Joint NIH-FDA Leadership 
Council is to optimize and maximize data from clinical trials. Would 
you consider working with the FDA to grant greater flexibility 
regarding the approval of orphan drug therapies on the basis of a 
single, well-designed trial?
    Answer. The FDA and the NIH have complementary roles and 
functions--the NIH supports and conducts biomedical and behavioral 
research and the FDA ensures the safety and effectiveness of medical 
and other products. The NIH does not share regulatory authorities with 
the FDA, i.e., we do not make decisions about regulatory pathways or 
the approvability of investigational products. However, we certainly 
have common goals and are working closely in a number of ways to 
address issues related to therapeutics development and regulatory 
science. As you noted, the agencies are working at the leadership level 
through the NIH-FDA Leadership Council, formed in 2010, to help ensure 
that regulatory considerations form an integral component of biomedical 
research planning and that the latest science is integrated into the 
regulatory review process. The challenges associated with the 
development and review of therapies for rare and neglected diseases, 
such as the availability of alternative regulatory pathways for trials 
of rare diseases and the level of scientific evidence needed for 
approval of a new orphan therapy, are among the specific topics of 
mutual interest. We also collaborate closely on issues associated with 
the development of new cancer diagnostics and therapeutics through an 
interagency oncology task force and, in accord with the provisions the 
Best Pharmaceuticals for Children Act, to advance the development of 
preclinical and clinical methodologies that provide optimal approaches 
for treating diseases in childhood. We believe all of these efforts can 
go a long way toward achieving our common goal of advancing public 
health by promoting the translation of basic and clinical research 
findings into medical products and therapies.
                                 ______
                                 
              Questions Submitted by Senator Thad Cochran

   TRANSFER OF THE IDEA PROGRAM TO THE NATIONAL INSTITUTE OF GENERAL 
                        MEDICAL SCIENCES (NIGMS)

    Question. The NIH has proposed the elimination of the National 
Center for Research Resources (NCRR). I am particularly concerned that 
this elimination will affect the Institutional Development Award 
(IDeA), which has benefitted my home State of Mississippi. Under the 
proposal, the IDeA program will be moved to the National Institute of 
General Medical Sciences. There have been concerns expressed that the 
IDeA program should not be placed in an Institute with a defined 
constituency. Dr. Collins, can you elaborate on the decision process 
for moving IDeA to the National Institute of General Medical Sciences? 
Why do you think this is the best Institute to house the IDeA program?
    Answer. The IDeA program fosters research and enhances the 
competitiveness of investigators at institutions located in States in 
which the aggregate success rate for applications to the NIH has 
historically been low. By its nature, the IDeA program extends beyond 
traditional capacity building in supporting research projects that are 
designed to strengthen future investigator-initiated research 
applications, most of which are aimed at addressing basic science 
questions. The National Institute of General Medical Sciences (NIGMS) 
has a basic science mission as well as a longstanding focus on 
institutional capacity building and career development. Given these 
synergies, the NIGMS was determined to be the optimal new home for the 
IDeA program. The NIH reached this conclusion based on a careful 
analysis of existing NCRR programs as well as extensive consultation 
with stakeholders across the scientific community and input from the 
NIH Institutes and Centers, including NCRR leadership and staff.

                      JACKSON HEART STUDY IMPACTS

    Question. African Americans are more likely to be diagnosed with 
coronary heart disease, and they are more likely to die from heart 
disease. Due to this greater prevalence, the Jackson Heart Study is 
exploring the reasons for this disparity and uncovering new approaches 
to reduce it. Can you discuss the impacts this study will have?
    Answer. The goals of the Jackson Heart Study (JHS) are to determine 
the roles of established risk factors such as obesity, dyslipidemia, 
and high blood pressure in the development and progression of 
cardiovascular disease (CVD) and to identify factors related to the 
emergence of such risk factors. Moreover, the study seeks to shed light 
on the contributions of sociocultural factors (e.g., stress, racism, 
discrimination, and coping strategies) and familial/hereditary factors, 
genetic variants, and gene--environment interactions to the development 
of CVD and its risk factors. Based on our experience with other NHLBI-
funded epidemiological studies of CVD such as the Framingham Heart 
study, we expect the JHS to provide important information that will 
help researchers to generate new hypotheses and design studies to test 
interventions to prevent CVD. Ultimately, we expect the results of the 
JHS to benefit not only Mississippians but also African Americans 
beyond the participants in the study.
    The JHS also seeks to build research capabilities in minority 
institutions, address the critical shortage of minority investigators 
in epidemiology and prevention, and reduce barriers to dissemination 
and use of health information in a minority population. The JHS 
educational and community outreach components are very strong; 
consequently, the research findings will be efficiently disseminated 
among participants. The JHS training component continues to provide 
outstanding opportunities to inspire, motivate, and educate students to 
become research leaders and to study and disseminate important findings 
on prevention of CHD.

                    STAFFING THE JACKSON HEART STUDY

    Question. The Jackson Heart Study is the largest epidemiologic 
investigation of Cardiovascular Disease among African Americans in the 
United States. The National Heart Lung and Blood Institute opened a 
field office in Jackson to provide scientific investigators and support 
staff to the study. It is my understanding that this one-person office 
will soon have no staff due to the staffer leaving Jackson. I am 
concerned that the National Heart Lung and Blood Institute may not fill 
the position quickly which would result in an adverse effect on the 
Jackson Heart Study. It is vital that the field site maintain strength 
to support scientific research at the Jackson Heart Study. Dr. Collins, 
can I have your assurance that the National Heart Lung and Blood 
Institute will replace this position in a timely manner?
    Answer. At present, the National Heart, Lung, and Blood Institute 
(NHLBI) medical officer stationed at the Jackson Heart Study site plans 
to remain there indefinitely. Should the position become vacant in the 
future, the NHLBI would promptly pursue recruitment via standard 
competitive procedures.

          GEOGRAPHIC HEALTH DISPARITIES FOR STROKE AND OBESITY

    Question. Health disparities are persistent across ethnic 
populations as well as geographically. Geographic isolation, 
socioeconomic status, and health risk behaviors contribute to health 
disparities in these rural communities. Mississippi is part of the 
``Stroke Belt'' and has the highest rate of obesity in the Nation. Both 
of these issues are persistent problems in the rural South, with 10 out 
of 11 States with the highest rates of obesity being in the South. Dr. 
Collins, how is the NIH addressing the geographic issues associated 
with many of the most serious diseases affecting our Nation?
    Answer. The NIH supports a broad portfolio of research to 
understand the complex factors that contribute to obesity, stroke, and 
related health problems, and to develop and evaluate prevention and 
treatment strategies for diverse populations.
    The Look AHEAD clinical trial, supported by the National Institute 
of Diabetes and Digestive and Kidney Diseases (NIDDK) and other NIH 
components, is determining whether lifestyle intervention improves 
health in overweight/obese people with type 2 diabetes, and in 
particular the impact of the intervention on the incidence of 
cardiovascular events, including stroke, heart attack, hospitalized 
angina, and cardiovascular-related death. For the first four years of 
this long-term study, participants in the lifestyle intervention group 
lost more weight and improved their blood pressure, fitness, glucose 
control, and good cholesterol, with less use of medication, compared 
with those in the control group. Look AHEAD includes sites across the 
country, including in Alabama, Louisiana, and Tennessee.
    A major National Institute of Neurological Disorders and Stroke 
(NINDS)-funded epidemiological study related to the ``Stroke Belt'' is 
the REGARDS study (REasons for Geographic and Racial Differences in 
Stroke) in which investigators are exploring the geographical and 
racial differences in stroke risk in a cohort of about 30,000 
individuals, about half of whom reside in the Stroke Belt region of the 
United States. This study also includes measures of functional 
cognitive decline, which may be a risk factor for stroke as well as a 
marker for unrecognized stroke. Data generated from this study has led 
to more than 70 publications, and will continue to help researchers 
pinpoint the reasons that the stroke death rate is higher in this 
region, and among African Americans, and to develop targeted strategies 
for intervention. Recent data from REGARDS indicated that overall time 
spent in the Stroke Belt is more predictive of hypertension--a powerful 
risk factor for stroke--than is current residence in the Stroke Belt. 
Data from the REGARDS study have also revealed that stroke survivors 
were more likely to have unrecognized hypertension and diabetes.
    To improve stroke care utilization and patient outcomes among 
vulnerable populations, the NINDS also invests in research to increase 
stroke awareness and reduce the time from symptom onset to hospital 
arrival, so that patients can be evaluated and treated in a timely 
manner.
    In one such study, a novel behavioral intervention will be tested 
in which children in high risk, minority communities are taught through 
Hip Hop Stroke (stroke rap songs and animated musical cartoons) to 
recognize and act on the five cardinal stroke symptoms and the 
importance of early treatment, with the hopes that they will 
communicate this information to their parents. Preliminary pilot data 
indicated that 74 percent of children communicated the material to 
their parents, which significantly improved their stroke knowledge.
    In the SWIFT (Stroke Warning Information and Faster Treatment) 
study, a culturally sensitive educational intervention focused on 
improving knowledge retention and time of arrival to the emergency 
department has been tested in minority communities. The outcome and 
results of this study are currently under review in a major medical 
journal.
    The ASPIRE program (Acute Stroke Program of Interventions 
addressing Racial and Ethnic disparities) is currently testing 
strategies to overcome community/socio-cultural and system barriers to 
stroke treatment with the goal of increasing the number of stroke 
patients treated with the clot-busting drug, tissue plasminogen 
activator (tPA), in six Washington, DC, hospitals.
    Ten years ago, the NINDS convened a Stroke Progress Review Group 
(SPRG) to identify and prioritize scientific opportunities in stroke 
research. In 2011, the NINDS will embark on a new stroke planning and 
evaluation effort, which will identify a specific set of high priority 
areas for advancing stroke research over the next 5-10 years. The topic 
of health disparities in stroke will be included as a cross cutting 
topic in this effort.

                    CARDIOVASCULAR DISEASE RESEARCH

    Question. Cardiovascular Disease is the leading cause of death in 
Mississippi, accounting for more than 40 percent of all deaths. In 
2004, the State of Mississippi implemented a 10-year plan to address 
Cardiovascular Disease risk factors in a two-fold approach: prevention 
of potential risk factors and management of existing risk factors. In 
addition, the Jackson Heart Study is the largest investigation of 
causes of Cardiovascular Disease in an African-American population. 
While both initiatives are good starts to addressing this health issue 
in my home State, Cardiovascular Disease is the number one killer in 
the United States and we need comprehensive research to fight the 
disease nationwide. What plans do you have to increase research in the 
area of Cardiovascular Disease?
    Answer. The NHLBI is committed to supporting a comprehensive 
research program on the causes, prevention, diagnosis, treatment, 
monitoring, and management of cardiovascular disease (CVD). We invest 
63 percent of the NHLBI extramural budget in CVD research, and we 
intend to continue that high level of support. This year, the Institute 
has launched a number of new projects, including two major clinical 
trials:
  --The International Study of Comparative Health Effectiveness with 
        Medical and Invasive Approaches (ISCHEMIA) addresses management 
        of patients with stable coronary heart disease who have 
        substantial ischemia on a cardiac stress test. The trial will 
        evaluate whether an invasive approach (performing an angiogram 
        and then opening or bypassing any blockages with stents or 
        surgery) plus optimal medical therapy is better than optimal 
        medical therapy alone in forestalling CVD events. Quality of 
        life and cost-effectiveness will also be assessed.
  --The Cardiovascular Inflammation Reduction Trial (CIRT) addresses 
        cardiovascular disease risk reduction in heart-attack survivors 
        with persistently high levels of C-reactive protein, an 
        indicator of inflammation. The trial will evaluate whether a 
        very low dose of the anti-inflammatory drug methotrexate 
        reduces rates of recurrent heart attack, stroke, and 
        cardiovascular death. Several other conditions that have an 
        inflammatory basis, such as diabetes, venous thromboembolism, 
        and atrial fibrillation, will also be assessed.
    The NHLBI has responsibility for cardiovascular, lung, and blood 
diseases that affect millions of people worldwide. We will continue our 
longstanding emphasis on the support of a balanced research portfolio 
that addresses the many public health needs and scientific 
opportunities that fall within our mandate.
                                 ______
                                 
             Questions Submitted by Senator Lamar Alexander

    REORGANIZATION OF NATIONAL CENTER FOR RESEARCH RESOURCES (NCRR) 
                                PROGRAMS

    Question. In my State of Tennessee, the largest single Federal 
grant at one of the State's largest medical research institutions is a 
Clinical and Translational Science Award (CTSA), for $40 million. How 
will this program and others like it be affected by the dissolution of 
the NCRR, and the creation of the National Center for Advancing 
Translational Sciences (NCATS)?
    Answer. The NIH is committed to supporting each program currently 
housed within the NCRR; the proposed reorganization will not adversely 
affect the individual programs. Indeed, a careful programmatic 
evaluation concluded that important scientific synergies could be 
gained by moving NCRR programs to other NIH components with adjacent 
scientific missions. Staff responsible for administering and directing 
these programs will transfer with their respective programs to ensure 
continuity and oversight. With regard to the Clinical and Translation 
Science Awards (CTSA) program specifically, it is to be transferred to 
the proposed National Center for Advancing Translational Sciences 
(NCATS). The transfer was recommended by the NIH Scientific Management 
Review Board, a congressionally-mandated advisory committee to the NIH 
Director, and further supported by an internal NIH task force charged 
with assessing the optimal location for NCRR programs. The task force's 
analysis confirmed that the goals of the CTSA program were in close 
alignment with those of the new center. Decisions regarding the 
selection of individual CTSAs will continue to be made based upon each 
proposal's scientific merit and program relevance.

                          CTSA PROGRAM MISSION

    Question. Given the established focus of the NCATS on drug 
development, will the CTSA's continue to be able to build on the 
programs of training, career development for young investigators, 
research informatics, community engagement and clinical research 
infrastructure?
    Answer. The focus of the NCATS is to develop new and innovative 
approaches to conducting research across the therapeutic development 
pipeline, in the context of strengthening and streamlining the process 
itself. The CTSAs have the infrastructure and diverse expertise that 
supports translational research, including training and career 
development for the next generation of clinical investigators, 
informatics, and community engagement, and they will be integral to 
fulfilling the NCATS mission. The CTSAs are making important 
contributions in transforming translational research across the 
country, and the NIH is committed to building upon the program's 
successful efforts. Ensuring that the pipeline of new investigators is 
sufficiently equipped to tackle the challenges associated with 
translational science through training and mentoring is an inherent 
part of the NCATS mission and will continue to be an essential 
component of the CTSAs.

                         PERSONALIZED MEDICINE

    Question. Physicians and researchers in Tennessee are investing a 
great deal in the science of personalized medicine. Can you tell us 
what the term ``personalized medicine'' means to you, and what role you 
see for the NIH?
    Answer. The concept of ``personalized medicine'' is based on the 
idea that one size does not fit all when it comes to the practice of 
medicine. Knowledge gathered from basic research and clinical studies 
have demonstrated that individuals are highly unique in their 
susceptibility to disease, reaction to medical treatments, and response 
to environmental and social factors. More than ever before, and largely 
thanks to research supported by the NIH, we now have the tools to 
understand, describe, and quantify these biological differences as well 
as the power to better predict which available treatments are optimal 
for certain patients and to design rationale-based new targeted-based 
therapies.
    The NIH will continue to play a pivotal role in the advancement of 
personalized medicine. For example, our support for pharmacogenomics 
research will advance understanding of the predictive roles and 
influences of genes in drug response. Findings from such research can 
help identify the right drug for the right patient at the right time. 
Increasingly, this information will help doctors calculate dosages that 
match a person's unique physiology. Pharmacogenomic information already 
is contained in approximately 10 percent of FDA-approved drug labels, 
helping to prevent the inappropriate use of diagnostics and therapies. 
Pharmacogenomic knowledge can also reduce the financial, emotional, and 
physical costs associated with the current trial-and-error based 
approach to treatment. Knowing each patient's DNA sequence is expected 
to add efficiencies and new research capabilities to current endeavors. 
As such, we are also fostering technological advances that are expected 
to bring down the cost of sequencing an individual genome to under 
$1,000. These advances will help make genetic analysis a routine part 
of medical care and a revolutionary factor in approaches to basic 
research and practice.

                             DNA DATABANKS

    Question. Several major research institutions are creating 
databanks that allows researchers to access a large collection of human 
DNA. How does the NIH also plan to build on the mapping of the human 
genome by optimizing unique resources such as this?
    Answer. In support of its mission to improve public health through 
research, the NIH has a longstanding policy of making data publicly 
available from the research that it funds. The NIH recognizes that data 
sets are not only valuable for addressing the questions that the 
experiments that generated them were designed to ask, but also can be 
powerful resources when combined with other data sets or used to answer 
other scientific questions. This is particularly true of DNA data sets 
that consist of information across the full sequence of the human 
genome. Consequently, building on the data sharing practices that 
characterized the Human Genome Project, the NIH launched research 
programs to stimulate the creation of genomic resources and created 
policies and tools for facilitating the sharing of genomic data to 
capitalize on the databanks created by other institutions with or 
without the NIH funding.
    For example, under the leadership of the National Human Genome 
Research Institute (NHGRI) the International HapMap Project used the 
reference human genome sequence to build a comprehensive map (database) 
of the variation within human DNA sequences, so that ``spelling'' 
differences in the DNA code of those with disease and those without 
disease could be identified and studied. The 1000 Genomes Project is 
now capitalizing on technological advances to extend and deepen the 
HapMap data. All data from each of these projects are publicly 
available to any investigator through the web with regular updates as 
new data are generated.
    In addition, to leverage the infrastructure and databank resources 
created at other research institutions, the NIH has introduced funding 
programs, such as the NHGRI-supported Electronic Medical Records and 
Genomics (eMERGE) Network. This consortium of U.S. medical research 
institutions has the primary goal of developing, disseminating, and 
applying approaches to research that combine existing DNA 
biorepositories with electronic medical record (EMR) systems for large-
scale, high-throughput genomic research. eMERGE Network institutions 
use their own databanks (e.g., Vanderbilt University's BioVU DNA 
databank) for this program, but all data are shared through an NIH 
database, the database of Genotypes and Phenotypes (dbGaP), which 
provides centralized and consistent access to researchers around the 
globe. Importantly, dbGaP includes not only eMERGE data, but data from 
studies across the disease spectrum. Extremely rich databanks from 
studies such as the Framingham Heart Study, The Cancer Genome Atlas, 
and many other projects reside within dbGaP, enabling many more 
investigators to analyze the data as independent or combined data sets. 
The standardization of access supported by the NIH facilitates cross-
study analyses, enables expansion of the study design beyond the 
initial research focus of the individual databanks, and increases the 
statistical power to identify the genetic contributors to common 
diseases that create substantial public health burden. And, 
importantly, all of these benefits are achieved through robust data 
sharing policies intended to protect the interests of the research 
participants who contribute their personal information to the 
individual databanks.

                INDUSTRY INVESTMENT IN GENOME SEQUENCING

    Question. How does private investment in genome sequencing help to 
leverage the Federal investment of genomic research through the NIH 
funding?
    Answer. The sequencing of the human genome has rightly been 
regarded as one of the most important scientific undertakings of the 
modern era. The NIH's investment in genomics has been, and continues to 
be wide-ranging, from basic research to uncover and understand the 
structure of our genome to translational science aimed at using a 
patient's DNA code to tailor treatment. Enabling all of this research 
are innovative new tools for DNA sequencing that have precipitated a 
drop in the cost of sequencing an individual genome from hundreds of 
millions of dollars to $15,000 or less.\2\ In the process, an entire 
industry of genomics-focused companies has been created, one that, 
according to a recent study conducted by Battelle Technology 
Partnership Practice, has generated an economic contribution of almost 
$800 billion since the start of the Human Genome Project.\3\ \4\
---------------------------------------------------------------------------
    \2\ Additional information on sequencing costs is available at 
http://www.genome.gov/27541954.
    \3\ http://www.battelle.org/publications/humangenomeproject.pdf.
    \4\ Additional information on the economic impact of the human 
genome project is available at http://www.genome.gov/27544383.
---------------------------------------------------------------------------
    The field of genomics has benefited from a combination of public 
and private investment. During the course of the last 10 years, the 
National Human Genome Research Institute's Genome Technology Program 
has provided support for the development of almost all of the currently 
commercialized, as well as several yet-to-be-commercialized or 
emerging, sequencing technologies. Private investment during and since 
that initial period of the NIH support has and will continue to bring 
these innovative advances to the market. Newer and increasingly cheaper 
sequencing machines and reagents have increased both capacity and 
productivity, enabling the NIH grantees to answer more research 
questions in the same period of time and for the same cost as 
previously. Illumina and Life Technologies, for example, have now 
developed smaller and less expensive sequencing machines that are 
bringing DNA sequencing within reach of single-investigator research 
labs. Affordable access to these technologies will greatly amplify the 
number of researchers that can employ genomic sequencing within their 
research plans, expanding the benefit of the Federal investment in 
genomic sequencing into yet more basic, translational, and clinical 
research domains. Companies like Illumina and Complete Genomics are 
also offering sequencing services that the NIH-funded researchers have 
used to great effect, such as the discovery last year of the causative 
genes behind rare disorders like Miller syndrome, something that had 
eluded science until now.\5\
---------------------------------------------------------------------------
    \5\ http://www.sciencemag.org/content/328/5978/636.
---------------------------------------------------------------------------
                                 ______
                                 
             Questions Submitted by Senator Lindsey Graham

                  EOSINOPHILIC DISORDERS WORKING GROUP

    Question. I have heard from individuals in my State about the 
enormous challenges to children with eosinophilic disorders and their 
families. I understand that these conditions are often misdiagnosed and 
there is no cure for these children, many of whom suffer from extreme 
pain and are unable to eat normal food. This subcommittee has asked 
that the NIH convene a working group on this topic. When will this 
group meet and when can we expect to have a report of the group's 
recommendations?
    Answer. Eosinophilic gastrointestinal disorders (EGID) are a group 
of diseases characterized by a wide variety of gastrointestinal 
symptoms including abdominal pain, swallowing problems, food impaction 
(food lodged or wedged in the esophagus), vomiting, diarrhea, growth 
impairment and bleeding. EGIDs are associated with increased numbers of 
eosinophils, a type of white blood cell, in the gastrointestinal 
lining. The most common EGID, eosinophilic esophagitis, is 
characterized by inflammation and accumulation of eosinophils in the 
lining of the esophagus. This disease and other EGIDs are diagnosed by 
a patient's clinical history plus endoscopy with biopsy.
    As the lead Institute at the National Institutes of Health (NIH) 
responsible for research on immunologic and allergic disorders, the 
National Institute of Allergy and Infectious Diseases (NIAID) works 
closely with other NIH Institutes and Centers supporting research on 
eosinophilic disorders. Although these collaborations and 
communications do not occur through a formal working group or a 
predetermined research agenda, they have led to jointly sponsored 
workshops and research initiatives on eosinophilic disorders. In fiscal 
year 2012, the NIH, with the NIAID as the lead, will establish a 
working group with participation by relevant NIH Institutes and 
Centers, to develop a trans-NIH strategy to improve the diagnosis and 
treatment of eosinophilic disorders.
    As part of its overall research agenda on immunologic and allergic 
diseases, the NIAID pursues research on eosinophilic disorders through 
a variety of efforts and collaborations. For example, the Consortium of 
Food Allergy Research (CoFAR), co-funded with the National Institute of 
Diabetes and Digestive and Kidney Diseases (NIDDK), and renewed in 
fiscal year 2010, develops new approaches to treat and prevent food 
allergy. A new CoFAR project is examining the genetic aspects of 
eosinophilic esophagitis. The NIAID Asthma and Allergic Diseases 
Cooperative Research Centers (AADCRC) support basic and clinical 
research on the mechanisms, diagnosis, treatment, and prevention of 
asthma and allergic diseases, including food allergy and anaphylaxis. 
Many of these disorders are associated with eosinophilia. In addition, 
the NIAID-supported investigators are conducting a pilot clinical trial 
to determine the efficacy of swallowed glucocorticoids for the 
treatment of eosinophilic esophagitis, and developing novel noninvasive 
diagnostic tools for eosinophilic gastrointestinal diseases to reduce 
the number of endoscopies and biopsies that are currently performed. 
Also, on behalf of more than 30 professional organizations, Federal 
agencies, and patient advocacy groups, including the American 
Partnership for Eosinophilic Disorders, the NIAID coordinated the 
development of Guidelines for the Diagnosis and Treatment of Food 
Allergy in the United States. This document includes clinical practice 
guidelines for the diagnosis and management of eosinophilic esophagitis 
associated with food allergy. The guidelines were published in the 
December 2010 issue of the Journal of Allergy and Clinical Immunology 
and can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/21134576.
    The NIAID will continue its commitment to research and trans-NIH 
research collaborations on eosinophilic disorders to understand the 
mechanisms that mediate tissue injury when eosinophils accumulate. As 
part of this effort, in fiscal year 2011, the NIAID will recompete the 
AADCRC program.
                                 ______
                                 
               Question Submitted by Senator Jerry Moran

                 BUDGETARY EFFECTS ON THE NCI PROGRAMS

    Question. Dr. Collins, I recently visited the University of Kansas 
and was given a tour of the University's drug discovery, delivery, and 
development operation. This visit helped demonstrate to me not only the 
many elements that will become part of the application by the 
University for National Cancer Institute (NCI) comprehensive cancer 
center designation, but also the impressive role that the NCI's cancer 
centers play across the Nation. This network of centers drives basic 
research, brings individuals into clinical trials, and, most 
importantly, leads to the development of new treatment advances that 
will change the course of cancer for all Americans and individuals 
across the globe.
    While I understand that the University of Kansas' application for 
the NCI designation will be determined on its scientific merits, can 
you please explain how the NCI cancer center program will be affected 
by the proposed budgets of the NIH and the NCI?
    Additionally, considering possible scenarios for the fiscal year 
2012 budget, what will the effects of such scenarios be on current NCI 
programs and on the prospect for funding the review of new 
applications?
    Answer. The the NCI-designated Cancer Centers are an important part 
of the NCI's research portfolio, and they play a unique and valuable 
role in providing cutting-edge cancer care and access to the NCI-
sponsored clinical trials across the country. The final fiscal year 
2011 appropriation has already necessitated a 5 percent reduction in 
funding below fiscal year 2010 for the cancer centers, and it is 
difficult to predict how they will be affected by the resolution of the 
fiscal year 2012 budget.
    The NCI's first priority must be to preserve funding for Research 
Project Grants (RPGs). Ensuring support for as many new RPGs as 
possible will enable investigators, especially new investigators, to 
pursue novel ideas that will preserve the pipeline of innovative cancer 
research. This year, nearly every NCI program budget has had to be 
trimmed in order to award adequate, though reduced, number of new RPGs.

                          SUBCOMMITTEE RECESS

    Senator Harkin. Is there anything else that any one of you 
would like to state for the record now? If not--Yes.
    Dr. Collins. Well, Senator, I'd just like to thank you and 
this subcommittee for your steadfast support for biomedical 
research.
    All of us involved in this enterprise sitting here at this 
table, and many others who are not at the table, but who are 
engaged every day in this effort to try to find interventions 
for people with disease appreciate your support and your strong 
voice that, even in difficult times, medical research is 
basically a societal good.
    I think a society ultimately will be judged by the ways in 
which, even in difficult times, priorities are chosen.
    We think, in terms of alleviating suffering as well as 
encouraging our American competitiveness and our economic 
growth, that what we are able to do through NIH is a very good 
story indeed, but we appreciate the fact that you have convened 
this hearing and given us a chance to tell some of that story.
    Senator Harkin. Well, thank you very much, Dr. Collins, and 
I can just reciprocate then I'll join all my colleagues in 
thanking you and all of you and all your colleagues at the NIH, 
all the Directors, the people who work there, and through you 
the whole network of researchers, young and old, some of who 
have just come on, some who have been there for many years, to 
thank you for your outstanding public service. All of you, 
every single person engaged in NIH, thank you.
    The subcommittee will stand recessed.
    [Whereupon, at 11:45 a.m., Wednesday, May 11, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]
