[Senate Hearing 113-]
[From the U.S. Government Publishing Office]



 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2014

                              ----------                              


                        WEDNESDAY, MAY 15, 2013

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 2:30 p.m., in room SD-138, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Mikulski, Moran, Cochran, Shelby, 
and Boozman.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        GARY H. GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND 
            BLOOD INSTITUTE
        RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
        STORY C. LANDIS, Ph.D., DIRECTOR, NATIONAL INSTITUTE FOR 
            NEUROLOGICAL DISORDERS AND STROKE
        HAROLD E. VARMUS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE

                OPENING STATEMENT OF SENATOR TOM HARKIN

    Senator Harkin. The Senate Appropriations Subcommittee on 
Labor, Health and Human Services, and Education will please 
come to order.
    Today, we are privileged to have with us, again, as my 
longtime compatriot Arlen Specter used to say, ``The crown 
jewel of the Federal Government.'' That is our National 
Institutes of Health (NIH) here today for our budget hearing.
    So, Dr. Collins, we welcome you back to the subcommittee, 
and also, in alphabetical order, Dr. Tony Fauci, Director of 
the National Institute of Allergy and Infectious Diseases; Dr. 
Gary Gibbons, Director of the National Heart, Lung, and Blood 
Institute; Dr. Richard Hodes, Director of the National 
Institute on Aging; Dr. Story Landis, Director of the National 
Institute for Neurological Disorders and Stroke; Dr. Harold 
Varmus, Director of the National Cancer Institute.
    This is a perilous moment for NIH and, indeed, for the 
future of biomedical research in this country. Since fiscal 
year 2003, the end of the 5-year doubling effort, NIH funding 
has dropped in real terms by 22 percent. In other words, the 
purchasing power of NIH's appropriations has fallen by more 
than one-fifth over the past decade.
    This year, fiscal year 2013, NIH funding will drop in 
actual dollars by $1.7 billion below last year's level, almost 
entirely because of sequestration.
    As a result, NIH will award 700 fewer new research project 
grants this year than it did last. That means 700 fewer 
opportunities to investigate and possibly find the cures for 
cancer and Alzheimer's and diabetes and any number of diseases.
    Perhaps even more alarming, a researcher's chance of 
getting a grant approved by NIH will drop to just 16 percent. 
That is the lowest success rate in the history of NIH.
    That comes at the time when the potential for scientific 
breakthroughs has perhaps never been better. At the National 
Cancer Institute, the success rate will be just 12 percent. At 
other institutes, below 10 percent. That's abysmal.
    When you have less than a 1-in-10 chance of getting a 
grant, that's when our best and brightest young minds start 
asking, ``What's the point? Maybe I need to find a different 
career.''
    It's no wonder that some are saying our Nation's status as 
the undisputed world leader in biomedical research is under 
threat.
    The President's budget request offers a welcome response to 
this disturbing decline. His budget calls for $31.1 billion for 
NIH in fiscal year 2014, which would not only reverse all of 
the cuts that are occurring this year but result in an increase 
over the fiscal year 2012 level. Included in that increase is 
$40 million to the new Brain Research through Advancing 
Innovative Neurotechnologies (BRAIN) Initiative, which I'm sure 
we'll hear more about.
    And I read your testimony last night, you mention that, 
both Dr. Collins and, I'm sure, Dr. Landis.
    So I want to do everything I can to help boost NIH's budget 
this year. I suspect that many Senators on the other side of 
the aisle also agree with this. NIH enjoys more bipartisan 
support than perhaps any other Agency in the entire Labor-HHS 
appropriations bill.
    But here's a problem. At the same time some of my 
colleagues are requesting a strong commitment to NIH funding, 
they also want sequestration to continue in fiscal year 2014. 
Some even want deeper cuts to nondefense discretionary spending 
next year to pay for some more increases in defense spending.
    There simply is no way to square these two priorities. I 
can promise you, if sequestration stays in effect next year, 
there's no chance that we will get close to the President's 
request for NIH, let alone back to the fiscal year 2012 level. 
It just won't happen.
    We are not going to savage other functions in education, 
health, labor, Centers for Disease Control and Prevention, and 
others, which are already at minimal levels. I will not get 
engaged in pitting NIH against other worthwhile endeavors in 
this appropriations bill.
    This is just one of the many reasons why we need to replace 
sequestration with a mix of targeted, responsible spending 
cuts, not just blind cuts to everything, and, yes, increased 
revenue.
    This sort of balanced approach is the only way NIH will 
have the resources it needs to realize the enormous scientific 
opportunities that we'll hear about shortly from our witnesses.
    First, I'll yield to Senator Moran for his opening 
statement.

                    STATEMENT OF SENATOR JERRY MORAN

    Senator Moran. Mr. Chairman, thank you very much, and let 
me thank you and your staff for the continual effort for us to 
work together to find a path forward on a Labor-H bill. I very 
much appreciate the attitude and approach that our staffs, and 
you and I, are taking.
    And I appreciate Dr. Collins and the other center directors 
being here today. This is a highlight, I think, for our 
subcommittee as we hear of some of the most recent and exciting 
developments as we face the challenges that disease provides.
    Science and research are the foundation of innovation, 
growth in our economy, and the solution to a myriad of issues 
that confront the health and well-being of our Nation. NIH 
funding biomedical research is the catalyst behind many of the 
advances that are now helping Americans live longer and 
healthier lives.
    Because of the Federal investment in biomedical research, 
U.S. cancer rates are now falling 1 percent each year, with 
each 1-percent decline saving our Nation about $500 billion.
    The U.S. death rate from heart disease and stroke have 
declined more than 60 percent in the last half century. And 
between 1997 and 2006, the death rate among adults with 
diabetes declined 23 percent.
    However, health advances aside, and they are paramount, the 
reduction of healthcare costs in the future may be one of the 
most significant contributions to society that medical research 
provides.
    As baby boomers age, the cost of healthcare will continue 
to increase. For example, a study led by the economists at the 
RAND Corporation stated that the cost of dementia care is 
projected to double over the next 30 years, surpassing 
healthcare expenses for both heart disease and cancer. Without 
a way to prevent or cure or effectively treat dementia, it will 
be difficult, if not impossible, to rein in costs.
    But science has confronted similar health challenges in the 
past and has prevailed. In the mid-20th century, economists 
predicted polio would cost taxpayers $100 billion a year to 
treat patients in iron lung hotels. In the face of this 
challenge, medical research produced a solution to this 
devastating disease, and polio is now on the verge of being 
eradicated worldwide.
    In the next few years, we confront difficult spending 
choices. And I believe we must prioritize our Federal 
commitment to NIH. It is crucial that our next generation of 
biomedical researchers, the ones who will develop better and 
more cost-effective healthcare, remain in the scientific 
research field.
    Without adequate and sustained Federal support for medical 
research, trainees will be driven from medical fields, or into 
the arms of our global competitors.
    Last year, China's Government pledged to increase basic 
research investment by 26 percent and will contribute more than 
$300 billion to biotechnology over the next 5 years.

                           PREPARED STATEMENT

    In the last 5 years, China's percentage of science and 
engineering degrees earned by university students was more than 
double those earned here in the United States. Without 
continued investment in NIH, we jeopardize our current 
scientific progress, risk losing a generation of scientists, 
and stunt our Nation's global competitiveness.
    This is not a time to waver on America's commitment to NIH 
and to the health of all Americans.
    Mr. Chairman, thank you, and I look forward to working with 
you on these priorities.
    [The statement follows:]

               Prepared Statement of Senator Jerry Moran

    Thank you, Mr. Chairman. I appreciate Dr. Collins and the other 
Center Directors being here today to discuss funding for the National 
Institutes of Health (NIH).
    Science and research are the foundation of innovation, growth in 
our economy, and the solution to the myriad of issues that confront the 
health and well-being of our Nation. NIH-funded biomedical research is 
the catalyst behind many of the advances that are now helping Americans 
live longer and healthier lives. Because of the Federal investment in 
biomedical research, U.S. cancer death rates are now falling 1 percent 
each year, with each 1-percent decline saving our Nation about $500 
billion. U.S. death rates from heart disease and stroke have declined 
more than 60 percent in the last half-century. Between 1997 and 2006, 
the death rate among adults with diabetes declined by 23 percent.
    However, health advances aside--and they are paramount--the 
reduction of healthcare costs in the future may be one of the most 
significant contributions to society from medical research. As baby 
boomers age, the cost of healthcare will continue to increase. For 
example, a study led by economists at the RAND Corporation stated that 
the cost of dementia care is projected to double over the next 30 
years, surpassing healthcare expenses for both heart disease and 
cancer. Without a way to prevent, cure, or effectively treat dementia, 
it will be difficult, if not impossible, to rein in costs. But science 
has confronted similar healthcare challenges in the past and prevailed. 
In the mid-20th century, economists predicted polio would cost 
taxpayers $100 billion a year to treat patients in ``iron lung 
hotels.'' In the face of this challenge, medical research produced a 
solution to this devastating disease. Polio is now on the verge of 
being eradicated worldwide.
    In the next few years as we confront difficult spending choices, I 
believe we must prioritize our Federal commitment to NIH. It is crucial 
that our next generation of biomedical researchers, the ones who will 
develop better and more cost-effective healthcare, remain in the 
scientific research field. Without adequate and sustained Federal 
support for medical research, trainees will be driven from the medical 
field or into the arms of our global competitors. Last year, China's 
Government pledged to increase basic research investment by 26 percent 
and will contribute more than $300 billion into biotechnology over the 
next 5 years. In the last 5 years, China's percentage of science and 
engineering degrees earned by university students was more than double 
those earned by U.S. students.
    Without continued investment in the NIH we jeopardize our current 
scientific progress, risk losing a generation of scientists, and stunt 
our Nation's global competitiveness. This is not the time to waiver on 
America's commitment to the NIH and the health of all Americans.
    Thank you, Mr. Chairman.

    Senator Harkin. Thank you very much, Senator Moran.
    And we welcome back again Dr. Francis Collins, the 16th 
Director of the National Institutes of Health, a physician and 
geneticist noted for discoveries of disease genes and his 
leadership of the Human Genome Project, of which he was the 
director from 1993 to 2008. Dr. Collins received a B.S. from 
the University of Virginia, his Ph.D. from Yale, and an M.D. 
from University of North Carolina at Chapel Hill.
    Dr. Collins, your statement will be made part of the record 
in its entirety. And, again, the floor is yours. Please proceed 
as you so desire.

              SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS

    Dr. Collins. Well, good afternoon, Mr. Chairman and members 
of the subcommittee. I'm very pleased to be here with my 
colleagues to present the President's budget request for the 
National Institutes of Health for fiscal year 2014.
    This panel has a long history of supporting NIH's mission 
to seek fundamental knowledge and apply it in ways that enhance 
human health, lengthen life, and reduce suffering.
    My sincere thanks to you, Mr. Chairman, for your strong 
commitment to supporting biomedical research over these years. 
NIH and millions of patients are grateful for that leadership.
    But I'm here today to talk about the Administration's 
fiscal year 2014 budget request of $31.331 billion, which is a 
$471 million, or 1.5 percent, increase over fiscal year 2012. 
This budget request will enhance NIH's ability to support 
cutting-edge research and training of the scientific workforce, 
with the ultimate goal of speeding up development of new ways 
to improve human health.
    This request allocates resources to areas of extraordinary 
promise while allowing flexibility to pursue unplanned 
scientific opportunities and address unforeseen health needs.
    But even with these tremendous scientific opportunities 
before us, and our hopes for your support in fiscal year 2014, 
we cannot ignore the current fiscal situation. As the chairman 
has just said, this is a perilous moment.
    As you know, and despite this subcommittee's best efforts 
to avert it, sequestration took effect on March 27. Frankly, 
this has already dealt a devastating blow to NIH and to the 
entire biomedical research enterprise.
    We're absorbing a $1.7 billion cut to our budget--and 
without action by this Congress, that will result, from the 
sequester, in a loss of $19 billion over the next 10 years.

                          NIH PURCHASING POWER




    This graph that I'm showing you shows in blue the 
appropriated levels to NIH and the effects of inflation in 
orange. So including the sequester, which you can see 
identified by this red arrow, that leads to a significant 
downturn in fiscal year 2013, and which we hope will turn back 
up again with the President's budget proposal for 2014, almost 
22 percent of the purchasing power for research has been lost 
versus 10 years ago, as you stated, Mr. Chairman.
    The consequences are stark. Look back at 2003. At that 
point, as a direct result of the efforts of this subcommittee, 
NIH was supporting a total of 38,216 research project grants. 
Now, a decade later, with all the scientific opportunity in 
front of us, that number has fallen by more than 3,300 grants. 
And the drop is particularly severe in fiscal year 2013, where 
we'll be funding 700 fewer new and competing research project 
grants done in fiscal year 2012. Which of those grants might 
have led to the next big discovery in cancer research or 
launched a career of a promising young scientist? We will never 
know.
    The paradox of my directorship at this time of 
unprecedented scientific opportunity, when we should be making 
progress by leaps and bounds towards curing human disease, is 
that our resources are suffering a historic downturn.
    This cut in support in biomedical research in the U.S. is 
particularly troubling when one considers the investments being 
made in the rest of the world, as Senator Moran has referred 
to.

              WORLDWIDE INVESTMENT IN BIOMEDICAL RESEARCH




    This bar graph is really quite striking, and I don't think 
anyone can look at it without being troubled by its 
significance. It shows the relative increases in support for 
biomedical research by countries around the globe. And you will 
notice the United States stands out on this graph in a very 
troubling way.
    Mr. Chairman, I cannot gloss over the severity of this 
situation. The potential damage to scientific momentum, 
economic growth, and morale is profound.
    Despite these trying times, NIH has continued to pursue our 
mission and has been accelerating scientific discovery in 
several key areas, and I'd like to highlight a couple of those.

                    CANCER: DECREASE IN DEATH RATES




    Let's consider cancer. One person dies from cancer every 
minute in the United States. NIH research has contributed to 
real progress with cancer death rates falling by 1 percent per 
year for the last 15 years, as already cited by Senator Moran. 
Economists estimate that each 1 percent drop is saving the U.S. 
$500 billion, making this an extremely good investment. But we 
are actually positioned to do much more.

                     THE CANCER GENOME ATLAS (TCGA)




    The Cancer Genome Atlas, or TCGA, is a coordinated effort 
to accelerate our understanding of the molecular basis of 
cancer using dramatic advances in genome sequencing 
technologies to carry out comprehensive analysis of more than 
20 types of cancer. By identifying the molecular changes in a 
cancer cell, as compared to a healthy cell of the same 
individual, we are gaining a better understanding of the 
driving forces behind the disease.

                 NIH-FUNDED RESEARCH MAJOR DEVELOPMENTS




    For example, very recently, NIH-funded researchers reported 
a major development. And in a study widely reported in the news 
media, they discovered that the genetic profile of a deadly 
form of uterine cancer closely resembles the profiles of the 
most lethal ovarian and breast cancers. This result has 
dramatic implications for prognosis and treatment.
    And this breakthrough, and others like it, is leading to 
the identification of new therapies tailored to the patient's 
unique genetic profile that can empower personalized 
interventions, and precision medicine instead of one-size-fits-
all chemotherapy.

                         STEM CELL ADVANCEMENTS




    Another example of how NIH-supported research is advancing 
biomedical discovery is in the area of stem cells. Induced 
pluripotent stem cells, also known as iPS cells, are 
revolutionizing the way we study disease. iPS cells are mature 
cells typically derived from a patient's skin that researchers 
can reprogram back to an immature state. These cells can then 
be programmed into a wide variety of cell types, including 
liver cells, neurons, or blood cells.




    This means we can start with a skin biopsy from a patient 
and then re-create that same individual's disease in a Petri 
dish. We can learn molecular details about the disease and even 
test potential drugs to see if they are likely to be safe and 
effective. It may one day even be possible to use these cells 
therapeutically. You can imagine how this might work, for 
instance, for a disease of the blood, such as sickle cell 
anemia. But we're not stopping there.

                  NEW INITIATIVES IN FISCAL YEAR 2014




    I'd like now to focus on a landmark new scientific endeavor 
that we're planning for fiscal year 2014. Neurological and 
psychiatric disorders such as Alzheimer's disease, Parkinson's 
disease, autism, schizophrenia, epilepsy, and traumatic brain 
injury inflict a tremendous toll on society yet their 
underlying pathology has remained largely unknown due to the 
enormous complexity of the human brain.
    This complexity, built on 86 billion neurons--that's what 
you got up there--each with thousands of connections was once 
thought to be beyond the reach of scientific understanding. 
Today, however, tremendous strides in neuroscience have created 
new opportunities for unlocking these mysteries and have placed 
us in the position of proposing a truly bold new initiative.

                            BRAIN INITIATIVE




    And so in fiscal year 2014, NIH will begin its support of 
the Brain Research through Advancing Innovative 
Neurotechnologies, B-R-A-I-N, the BRAIN Initiative. The goal of 
this initiative is to accelerate the development and 
application of new technologies that will enable researchers to 
produce dynamic pictures of the brain that show how individual 
brain cells and complex neural circuits interact, all at the 
speed of thought.
    To do that, we need to be able to record signals in much 
greater numbers of brain cells at a much more rapid pace than 
is currently possible. And while recent innovations like 
functional magnetic resonance imaging (MRI) have contributed 
substantially to our expanding knowledge of the brain, 
significant breakthroughs on how we treat neurological and 
psychiatric disease will require a new generation of tools.
    By measuring activity at the scale of circuits and networks 
in living organisms, we can begin to translate data into models 
that will decode sensory experience, motor activity, and 
potentially even memory, emotion, and thought. So how do we set 
about doing this?

                        HUMAN CONNECTOME PROJECT




    Another major NIH initiative has already laid the 
groundwork for mapping the human brain, the Human Connectome 
Project. This is an image, a noninvasive image, of a healthy 
human being, using a new kind of MRI. This connectome depends 
upon a dramatic set of advances in MRI scanning, giving this 3-
D picture of a wiring diagram of nerve cells in your brain.
    Interestingly, this proves that you are more than just your 
deoxyribonucleic acid (DNA). Environmental factors and life 
experiences work in concert with genetics to create your unique 
neural connections. And this is where the BRAIN Initiative 
comes in. It is designed to develop technologies that are 
capable of recording the activity of hundreds of thousands of 
neurons in real time, allowing us to determine the way in which 
brain circuits actually function.

                    BRAIN INITIATIVE: LONG-TERM PLAN




    The BRAIN Initiative is ambitious, and the details of a 
plan that will stretch over a decade or more are being worked 
out. But we must begin now. The BRAIN Initiative will provide a 
better understanding of the roots of human neurological 
disorders, revolutionize the field of neuroscience, and set the 
stage for major advances in diseases that will catalyze the 
development of new treatments and cures.

                          DR. COLLINS' SUMMARY




    So, to sum up, today I've told you about the tremendous 
scientific progress we've already made and a few of the many 
fantastic opportunities that lie on the horizon. However, I 
need to drive home, again, the impact of sequestration.
    Let me close by putting a human face on exactly who is at 
risk during these trying fiscal times.

                       FUTURE OF YOUNG SCIENTISTS




    I recently met with Dina, one of my former superstar 
students, who spent 2 years working in my lab at NIH before 
deciding to go on to graduate school. She's now finishing her 
Ph.D. at MIT and has done spectacular work in developmental 
biology. But she sees what is happening to biomedical research 
in the United States, and she is sufficiently worried about her 
own future to begin to consider other options quite seriously.
    In fact, many of her contemporaries have begun looking for 
options outside of science or outside of this country. She 
wrote me these words after our recent meeting: ``Many of my 
role models--top scientists with amazing ideas and the 
potential to change the world--are unable to get funding. I 
can't erase the fear that this is my future.''

                          PREPARED STATEMENTS

    This is a defining moment. My fear is that we're putting an 
entire generation of U.S. scientists at risk. And if they go 
away, they won't come back.
    Sequestration is compromising the future of biomedical 
research and slowing improvement in the health of all 
Americans.
    So, thank you, Mr. Chairman. I look forward to answering 
any questions you and this committee may have.
    [The statements follows:]

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

    Good afternoon, Mr. Chairman and distinguished members of the 
subcommittee. I am Francis S. Collins, M.D., Ph.D., and I am the 
Director of the National Institutes of Health (NIH). Accompanying me 
today are: Anthony S. Fauci, M.D., Director of the National Institute 
of Allergy and Infectious Diseases; Gary H. Gibbons, M.D., Director of 
the National Heart, Lung, and Blood Institute; Richard J. Hodes, M.D., 
Director of the National Institute on Aging; Story C. Landis, Ph.D., 
Director of the National Institute for Neurological Disorders and 
Stroke; and Harold E. Varmus, M.D., Director of the National Cancer 
Institute.
    It is an honor to appear before you today to present the 
Administration's fiscal year 2014 budget request for the NIH.
    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 illness and disability. I can report 
to you that NIH leadership, employees, and grantees continue to believe 
passionately in our mission.
    NIH has been advancing our understanding of health and disease for 
more than a century, and scientific and technological breakthroughs 
generated by NIH-supported research are behind much of the gains this 
country has enjoyed in public health. For example, deaths from heart 
attack have fallen by more than 60 percent over the past 40 years; 
deaths from stroke by more than 70 percent. HIV/AIDS treatment and 
prevention may now enable us to envision the first AIDS-free generation 
since this virus emerged more than 30 years ago. More than 90 percent 
of children diagnosed today with the most common form of childhood 
leukemia will survive. NIH research has given us vaccines for cervical 
cancer, influenza, and meningitis. We can look forward to a future in 
which advanced prevention and treatment strategies such as these allow 
everyone to have a much better chance of living a long and healthy 
life.
    I would like to begin today by highlighting just a few areas in 
which NIH-supported research is opening up extraordinary new 
opportunities to improve the health of the American public.
    Let's consider cancer. One person dies from cancer every minute in 
the United States--that equates to 1,500 deaths every day, the 
equivalent of five crashing jumbo jets.\1\ NIH research has contributed 
to real progress, with cancer death rates falling by 1 percent per year 
for the past 15 years--but we aim to do much more. With the National 
Cancer Institute (NCI) and the National Human Genome Research Institute 
(NHGRI) as leads, NIH established The Cancer Genome Atlas (TCGA) as a 
coordinated effort to accelerate our understanding of the molecular 
basis of cancer, using dramatic advances in genome sequencing 
technologies to carry out comprehensive genomic analysis of more than 
20 types of cancer. By identifying the molecular changes in a cancer 
cell as compared to a healthy cell of the same individual, we are 
gaining a better understanding of the driving forces behind the 
disease. That is leading to identification of new drug targets, as well 
as of subsets of disease with different responses to therapy that can 
empower personalized interventions instead of one-size-fits-all 
chemotherapy. As an example, a TCGA research network of investigators 
recently identified promising new therapeutic targets in squamous cell 
carcinoma of the lung, the second most common form of lung cancer, 
including three families of enzymes that act as molecular switches.\2\ 
These findings lay the foundation for the development and 
implementation of advanced diagnostics and treatments for squamous cell 
cancer. Moreover, they underscore the value and promise of our Nation's 
investment in TCGA.
    Another new and exciting area of basic research is the Human 
Microbiome Project. Microbes inhabit many parts of the human body and 
have often had a bad reputation for causing sickness. But more often 
than not, they actually contribute to the health of their human hosts. 
In a 5-year endeavor supported by the NIH Common Fund, 200 scientists 
at 80 institutions sequenced the genomes of bacteria from multiple body 
sites of 250 individuals, with striking results. The research showed 
that certain communities of bacteria help keep people healthy, whereas 
others appear to make people more susceptible to disease.\3\ When the 
bacterial population in the intestinal tract gets disrupted, chronic 
conditions such as obesity can result; this new understanding may 
provide us with novel ways to address this serious health threat. An 
unexpected result from another NIH-funded study was that poor diet is 
not the only contributor to malnutrition. In fact, a bad assortment of 
microbes in the gut can conspire with a nutrient deficient diet to lead 
to severe malnutrition.\4\
    A final example I want to provide of how NIH-supported research is 
accelerating scientific discovery is in the area of stem cells. Induced 
pluripotent stem (iPS) cell technology is revolutionizing the way we 
study disease, and holds the promise of dramatic advances in treatment. 
iPS cells are patient-derived cells, typically from skin, that 
scientists can reprogram back to an embryonic stem cell-like state. 
These cells can then be induced to turn on specific sets of genes to 
differentiate into a variety of cell types, including blood cells, 
liver cells, or neurons. This means researchers can re-create a 
patient's disease in a dish and screen drug compounds against the 
cells--rather than the patient--to determine drug toxicity and 
efficacy. But it's also possible that these cells could be used 
therapeutically, especially if an individual's genetic misspellings 
could be corrected in their own iPS cells, and then programmed and 
delivered to a tissue where they are sorely needed. Recent NIH-funded 
studies have developed copy-editing enzymes that are making it faster, 
easier, and cheaper to correct genetic typos. In 2011, researchers used 
a specially engineered copy-editing enzyme to find and correct the 
mutation that causes sickle cell anemia using iPS cells derived from a 
patient with the disease.\5\ Two very recent, groundbreaking 
discoveries along this same avenue are the development of the next 
generation methodology of ``find and replace'' enzymes that are making 
it much simpler to copy-edit the genome.\6\ \7\
    While these exciting findings have led to a much deeper 
understanding of health and human disease, much more work needs to be 
done in order to move these strategies and others like them out of the 
lab and into the clinic--and to do so as quickly as possible. To this 
end, the Administration's fiscal year 2014 budget request for the NIH 
is $31.331 billion, $471 million above the fiscal year 2012 level. This 
budget request reflects the President's and the Secretary's commitment 
to improving the health of the Nation and to maintaining our Nation's 
leadership in the life sciences. The request highlights investments in 
innovative research that will advance fundamental knowledge and speed 
the development of new therapies, diagnostics, and preventive measures 
to improve public health.
    The fiscal year 2014 budget request, a 1.5-percent increase over 
fiscal year 2012, will enhance NIH's ability to support cutting-edge 
research and training of the scientific workforce. Within the 
Administration's fiscal year 2014 budget, we will continue to increase 
Research Project Grants (RPGs), NIH's funding mechanism for 
investigator-initiated research. NIH expects to support 10,269 
competing RPGs in fiscal year 2014, an increase of 1,283 over fiscal 
year 2012 levels. For fiscal year 2014, NIH anticipates funding a total 
of 36,610 RPGs. The budget request allocates resources to areas of the 
most extraordinary promise for biomedical research, while maintaining 
the flexibility to pursue unplanned scientific opportunities and 
address unforeseen health needs.
    A major initiative for NIH in fiscal year 2014 will be in the area 
of Alzheimer's disease research. As many as 5.1 million Americans 
suffer this irreversible, progressive, and devastating brain disease 
that slowly destroys cognitive functions including memory and the 
ability to reason and think.\8\ At the same time, millions of American 
families struggle with the physical, emotional, and financial costs of 
caring for a loved one with Alzheimer's. A recently published NIH-
supported study found the costs of caring for people with dementia in 
the United States in 2010 ranged from $157 billion to $215 billion.\9\ 
This disease is not just a burden on our health, but also a burden on 
our economy.
    NIH, with the National Institute on Aging (NIA) taking the lead, 
currently supports a number of studies aimed at understanding, 
diagnosing, preventing, and treating Alzheimer's disease. In fiscal 
year 2014, NIA would plan to award a total of 591 new and competing 
RPGs, an increase of 277 from fiscal year 2012. This includes an $80 
million increase for Alzheimer's research.
    A seminal finding that has recently generated a lot of excitement 
is the discovery that the protein, tau, which appears to be in part 
responsible for the cognitive decline in Alzheimer's patients, spreads 
from neuron to neuron like an infection.\10\ This means that if 
researchers could find a way to prevent cell-to-cell transmission, 
perhaps by blocking tau with an antibody, the disease process could be 
halted. There is also growing evidence that successful treatment of 
Alzheimer's disease needs to happen very early in the course of the 
disease, perhaps even before any symptoms have appeared at all. This 
kind of Alzheimer's disease prevention is at the heart of new clinical 
trials being conducted by scientists at the Dominant Inherited 
Alzheimer's Network (DIAN), a NIA-funded international research 
partnership. One of the investigational drugs being tested is a 
monoclonal antibody that binds to certain forms of amyloid beta, a main 
constituent of the signature plaques in Alzheimer's disease. Trying to 
prevent Alzheimer's symptoms from ever occurring in individuals at very 
high genetic risk is a new strategy--one that we are eager to pursue in 
order to determine if early intervention can influence this terrible 
disease.
    With advancing scientific and technological capabilities, such as 
genome sequencing machines and high resolution medical imagers, 
biomedical researchers are generating huge amounts of data at an 
unprecedented pace. The need to integrate and analyze massively complex 
datasets is referred to as the Big Data challenge--a challenge that we 
must overcome to gain a deeper understanding of disease and develop the 
next generation of therapeutic targets.
    Managing Big Data is a critical part of translating scientific 
discoveries into clinical applications. To address this challenge, NIH 
is developing the Big Data to Knowledge (BD2K) program, which will be 
launched in fiscal year 2014. BD2K will support four programmatic 
efforts: (1) facilitate the broad use and sharing of large, complex 
biomedical data sets through the development of policies, resources and 
standards; (2) develop and disseminate new analytical methods and 
software; (3) enhance training of data scientists, computer engineers, 
and bioinformaticians; and (4) establish Centers of Excellence to 
develop generalizable approaches that address important problems in 
biomedical analytics, computational biology, and medical informatics. 
In fiscal year 2014, NIH will invest at least $40 million in the BD2K 
program through the Common Fund, and each Big Data Center of Excellence 
will be funded at $2 million to $5 million per year for 3 to 5 years. 
As Big Data challenges in biomedical research are shared with other 
areas of scientific research such as energy and space research, BD2K 
will also require effective collaboration and coordination with other 
Government agencies tackling similar challenges, including the National 
Science Foundation and the Department of Energy, as well as privately 
funded efforts. With the proper investments and efforts, we will 
overcome the challenges associated with Big Data in order to accelerate 
the translation of bench to bedside applications.
    Another exciting new initiative I would like to tell you about is 
NIH's efforts to recruit and retain a diverse pool of scientific talent 
and creativity. NIH is strongly committed to maintaining a diverse 
biomedical research workforce and has supported programs to enhance the 
diversity of our workforce for more than 30 years in order to achieve 
this goal. While progress has been made in some areas, more work needs 
to be done. The centerpiece of the newest initiative is the BUilding 
Infrastructure Leading to Diversity (BUILD) Program that is designed to 
provide relatively under-resourced institutions with the opportunity to 
provide a series of rigorous, mentored research experiences to their 
students, many of whom are from backgrounds underrepresented in 
biomedical research, with the goal of facilitating entry of a more 
diverse pool of students into graduate programs for biomedical 
research.
    I want to emphasize that while all of these ambitious new 
scientific endeavors provide unprecedented promise for advancing human 
health, we cannot ignore the impact the sequester is having on 
groundbreaking medical research. The fiscal year 2013 reduction of $1.6 
billion, or 5.0 percent, is having a substantial impact on the 
scientific community. If the Budget Control Act-imposed caps on 
discretionary programs continue, and NIH funding is reduced 
proportionally over the next 10 years, funding will decline by about 
$19 billion. The consequences will be harmful to scientific progress 
and to American leadership in science. NIH-funded investigators are 
already feeling the effects as Institutes and Centers are forced to 
fund a lower percentage of grant applications. In fiscal year 2012, we 
funded 8,986 competing RPGs. In fiscal year 2013, our projection is 
8,283. This trend is also reflected in our total research portfolio--we 
expect to fund 34,902 RPGs this year compared to 36,259 in fiscal year 
2012. With this new reality, more and more investigators will be unable 
to pursue the bold ideas that NIH has traditionally supported.
    NIH plays a significant role in the U.S. economy by advancing 
scientific products and technologies that help maintain our Nation's 
role as a global innovation leader.\11\ At a time when global 
competition in the life sciences is intensifying, the American economy 
cannot afford to lose ground in scientific efforts that promote human 
health. Countries such as China and India are increasingly investing 
resources into biomedical science and technology. According to the 
Organization for Economic Cooperation and Development (OECD), in 2008, 
including both public and private sources, the U.S. invested 2.8 
percent of its GDP in research and development (R&D)--less than Israel, 
Japan, Korea, Sweden, and Switzerland. Moreover, the U.S. ranks only 
eighth in R&D as a share of GDP among countries in the OECD.\12\ China 
has made policy changes to invest heavily in the life sciences 
industry, moving them closer to becoming a world leader in science and 
technology by the end of the decade.\13\ Over the past decade, 
Singapore has also pursued a prominent role as a global leader in the 
life sciences. For example, their pharmaceutical industry R&D funding 
was five times greater than that of the U.S. in 2009, on a share of GDP 
basis. Despite these factors, the United States is by far the largest 
R&D performer globally, contributing $402 billion in 2009, accounting 
for about 31 percent of the global total.\14\
    But let me close on a more positive note. I began today by telling 
you about some exciting new initiatives NIH is planning for fiscal year 
2014. Now I want to tell you about our boldest new scientific 
endeavor--one that we are all very excited about.
    Neurological and psychiatric disorders such as Alzheimer's disease, 
Parkinson's disease, autism, schizophrenia, and traumatic brain injury 
inflict a tremendous toll on society, yet their underlying pathologies 
remain unknown due to the great complexity of the human brain. This 
complexity was once thought to be beyond the reach of scientific 
understanding. Today, however, tremendous strides in neuroscience have 
brought forward remarkable new opportunities for unlocking these 
mysteries.
    Indeed, neuroscience has made some extraordinary progress in recent 
years. For example, a group of NIH-supported researchers has developed 
a sophisticated neural interface that enables paralyzed people to move 
a robotic arm, using just their thoughts. Using this robotic arm 
system, 58-year-old Cathy Hutchinson recently was able to take a sip of 
coffee on her own for the first time since she'd been paralyzed more 
than 14 years earlier. A truly remarkable moment--but just a beginning, 
because we need a lot more of these moments for a whole lot more 
people.
    In fiscal year 2014, NIH will begin its support of the Brain 
Research through Advancing Innovative Neurotechnologies (BRAIN) 
Initiative, in order to develop a deeper understanding of brain 
function through the creation of new tools capable of examining the 
activity of millions of nerve cells, networks, and pathways in real 
time. By measuring activity at the scale of circuits and networks in 
living organisms, we can begin to translate data into models that will 
decode sensory experience, motor planning, and, potentially, even 
memory, emotion, and thought. NIH is embracing a collaborative approach 
in tackling this challenge, working with researchers from across the 
country, industry, foundations, and other Government agencies including 
the Defense Advanced Research Projects Agency and the National Science 
Foundation. In fiscal year 2014, NIH will invest $40 million in this 
initiative to leverage investment from a number of other sources, 
including private sector and leading philanthropies. We believe that 
successful completion of the BRAIN Initiative will revolutionize the 
field of neuroscience and set the stage for major advances in diseases 
such as Alzheimer's, Parkinson's, autism, schizophrenia, depression, 
and epilepsy.
    Granted, this is a very ambitious goal. But we at NIH have heard 
and overcome such skepticism before. Take the example of the Human 
Genome Project, which I had the privilege to lead. In its earliest 
days, back in the late 1980s, many questioned the wisdom of that 
proposal to sequence the 3 billion letters in the human genetic 
blueprint. Nearly everyone in the research community agreed that it 
would be fantastic to have a full readout of the human DNA instruction 
book. But skeptics argued that it could not be done because the tools 
and technologies didn't exist. In fact, they were right--we didn't have 
the necessary technologies. But, the opportunity for dramatic progress 
in genetics inspired a remarkable series of technical innovations. 
These tools enabled the Human Genome Project to be successfully 
completed in April 2003, ahead of schedule and under budget. Like the 
Human Genome Project, we envision the BRAIN Initiative will create 
data, tools, and technologies that will speed the efforts of many 
different types of researchers all around the world. Though this 
program will need to extend over many years, and we must be careful not 
to overpromise immediate medical benefits, BRAIN will eventually lead 
to scientific advances that will catalyze development of new treatments 
and cures.
    I have provided you today with a brief overview of NIH's past 
successes and continuing commitment to basic and translational science, 
as well as a glimpse into the critical role that NIH plays in our 
domestic and global economies. We have never witnessed a time of 
greater promise for advances in medicine than right now. With your 
support, the future of medicine will be very bright.
    This concludes my testimony, Mr. Chairman.
---------------------------------------------------------------------------
    \1\ http://cancergenome.nih.gov/PublishedContent/Files/pdfs/
1.1.0_CancerGenomics_TCGA-Genomics-Brochure-508.pdf.
    \2\ http://www.nature.com/nature/journal/v489/n7417/pdf/
nature11404.pdf.
    \3\ http://www.nature.com/nature/journal/v486/n7402/pdf/
nature11209.pdf.
    \4\ http://www.sciencemag.org/content/339/6119/548.full.pdf.
    \5\ http://onlinelibrary.wiley.com/doi/10.1002/stem.718/pdf.
    \6\ http://www.sciencemag.org/content/326/5959/1501.full.pdf.
    \7\ http://www.sciencemag.org/content/339/6121/819.full.pdf.
    \8\ http://www.nia.nih.gov/alzheimers/topics/alzheimers-basics.
    \9\ http://www.nejm.org/doi/pdf/10.1056/NEJMsa1204629.
    \10\ http://www.plosone.org/article/
info%3Adoi%2F10.1371%2Fjournal.pone.0031302.
    \11\ http://www.unitedformedicalresearch.com/wp-content/uploads/
2013/02/UMR_Impact_of_
Sequestration_2013.pdf.
    \12\ http://www.itif.org/publications/winning-race-2012-memos-
science-and-technology.
    \13\ http://www.itif.org/publications/leadership-decline-assessing-
us-international-
competitiveness-biomedical-research.
    \14\ http://www.nsf.gov/statistics/seind12/c4/c4s8.htm.
---------------------------------------------------------------------------
                                 ______
                                 
              Prepared Statement of Anthony S. Fauci, M.D.

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute of Allergy 
and Infectious Diseases (NIAID) of the National Institutes of Health 
(NIH). The fiscal year 2014 NIAID budget of $4,578,813,000 includes an 
increase of $96,444,000 over the comparable fiscal year 2012 level of 
$4,482,369,000.
    NIAID conducts basic and clinical research with the ultimate goal 
of improving human health through the development of diagnostics, 
therapeutics, and vaccines for infectious diseases; and to increase our 
understanding of the immune system, how it protects us from infection 
and disease, and its role in immune-mediated diseases. NIAID also 
addresses the scientific challenges that arise from emerging and re-
emerging infectious diseases, including influenza, HIV/AIDS, 
tuberculosis, and malaria.

                      INFECTIOUS DISEASES RESEARCH

    HIV/AIDS.--Through more than 30 years of supporting and conducting 
basic and clinical research, NIAID has provided the scientific 
foundation for groundbreaking interventions and strategies to treat and 
prevent HIV/AIDS, including combination antiretroviral therapy (ART), 
pre-exposure prophylaxis (PrEP), medical male circumcision, prevention 
of mother-to-child transmission (PMTCT), microbicides, and 
antiretroviral treatment as prevention. It is an exciting time in the 
domestic and global fight against HIV/AIDS, and NIAID continues to 
support research critical to a goal now within our reach: an AIDS-free 
generation. The NIAID-funded HPTN-052 clinical trial--the ``Science'' 
magazine 2011 Breakthrough of the Year--conclusively demonstrated that 
treatment of the HIV-infected person in a stable heterosexual 
relationship with an uninfected partner dramatically reduces the 
likelihood of transmitting HIV to the uninfected partner. Recently, 
based upon results of the NIAID-funded iPrEx study and other research, 
the Food and Drug Administration (FDA) approved the ART combination 
drug Truvada as a prevention tool for uninfected adults at high risk 
of acquiring HIV. Ongoing NIAID studies of PrEP, microbicides, and 
PMTCT are exploring new strategies to limit HIV transmission in various 
populations; one study (TLC-Plus) is evaluating the feasibility of a 
community-level ``testing, link to care, and treatment'' strategy; and 
the new population-based ART study (PopART) will determine the effects 
of universal testing and immediate ART on HIV transmission.
    NIAID continues its longstanding efforts to develop an effective 
HIV vaccine. NIAID is currently investigating the reasons for the 
modest efficacy (31 percent protection) of the HIV vaccine candidates 
used in the RV-144 clinical trial conducted in Thailand several years 
ago, and will seek to achieve significantly better results with future 
vaccine candidates. In this regard, NIAID has funded two new HIV 
vaccine initiatives and also is moving into Phase I clinical trials to 
determine if passively transferred neutralizing antibodies can protect 
against HIV infection.
    Tuberculosis and Malaria.--Drug-resistant forms of tuberculosis 
(TB) are emerging worldwide, and co-infection with TB and HIV is a 
major cause of morbidity and mortality in the developing world. NIAID 
is helping to bring TB research into the 21st century by applying 
microbial genomic sequencing technologies, investing in the basic 
science underlying point-of-care diagnostics, supporting research to 
develop vaccine candidates, and engaging in public-private partnerships 
for drug development. These efforts are bearing fruit: NIAID 
researchers showed the potential of linezolid (originally developed for 
staphyloccocal infections) as a treatment for extensively drug-
resistant TB, and FDA recently approved the first new TB drug 
(bedaquiline) in decades.
    NIAID continues its work to combat malaria. To counter the emerging 
resistance to artemesinin, a first-line malaria drug, NIAID scientists 
have identified a region in the genome of the parasite linked to 
artemesinin resistance. NIAID is pursuing its promising efforts to 
develop candidate malaria vaccines, including studies conducted at the 
NIH Clinical Center.
    Other Infectious Diseases of Domestic and Global Health 
Importance.--Events in the news remind us almost on a daily basis of 
the global threat of emerging and re-emerging infectious diseases. 
Paramount among these are seasonal influenza and potential pandemic 
influenza threats, such as the H7N9 influenza emerging in China. NIAID 
conducts research on the pathogenesis and transmissibility of 
influenza, and the emergence of epidemics and pandemics, with the goal 
of furthering the development of influenza diagnostics, therapeutics, 
and vaccines. We have made significant strides toward developing a 
universal influenza vaccine, which would obviate the need for annual 
influenza vaccination and enhance our ability to respond to the 
emergence of influenza pandemics. Though it will be years before this 
goal is achieved, NIAID grantees and scientists, including those at 
NIAID's Vaccine Research Center, have demonstrated success in animal 
models, and have begun Phase I trials in humans. In addition, the NIAID 
Human Immunology Project Consortium is characterizing human immune 
responses to improve vaccines and immunotherapeutics for a variety of 
infectious diseases, including influenza.
    NIAID scientists have developed an animal model to study the novel 
coronavirus recently identified in Saudi Arabia, and to evaluate 
potential treatments and vaccines. They have shown recently that a 
combination of two antiviral drugs, ribavirin and interferon, can 
inhibit replication of the virus in cell culture.
    Common microbial infections are increasingly becoming resistant to 
the drugs generally used to treat them. Methicillin-resistant 
``Staphyloccus aureus'' (MRSA) has been a longstanding problem. Of 
particular concern is the recent emergence of other antibiotic-
resistant organisms such as the carbapenem-resistant Enterobacteriaceae 
(CRE) including ``Klebsiella pneumoniae''. To address the challenge of 
antimicrobial resistance, NIAID continues its efforts in the 
development and testing of vaccines to prevent these infections, and in 
the evaluation of new and repurposed drugs to treat antimicrobial-
resistant organisms. This year, NIAID will establish a leadership group 
for a national network to conduct clinical research on antibacterial 
resistance.
    We are witnessing rapid changes in the treatment of hepatitis C 
virus (HCV), a major cause of chronic liver disease and a common co-
infection with HIV. Promising new HCV protease inhibitor drugs recently 
approved by FDA were developed with the help of NIAID and other NIH 
Institutes. NIAID also is collaborating with industry to develop new 
HCV therapeutics and vaccines, and to test approved drugs in 
individuals with HCV/HIV co-infection.
    NIAID biodefense research continues to build on our fundamental 
understanding of the biology of and immune response to microbes. Recent 
successes include FDA approval of a monoclonal antibody to treat 
anthrax and progress on vaccines against Ebola and other hemorrhagic 
fever viruses. NIAID biodefense research also addresses the global 
threat of emerging and re-emerging diseases, including the development 
of vaccines for dengue fever and animal models to study West Nile 
virus.

          RESEARCH ON IMMUNOLOGY AND IMMUNE-MEDIATED DISORDERS

    NIAID remains committed to basic and clinical research on the 
immune system and immune-mediated diseases, including the development 
and testing of adjuvants to enhance the immune response to vaccination. 
NIAID also supports groundbreaking studies in the treatment of food 
allergy, a significant concern for many Americans. Recently, NIAID-
funded scientists found that oral egg immunotherapy can reduce and even 
eliminate allergic responses for extended periods in certain children. 
Similarly promising results showed that peanut immunotherapy given 
under the tongue can reduce the allergic response in adolescents and 
adults.

                               CONCLUSION

    NIAID conducts critical research on infectious and immune-mediated 
diseases that ultimately will enable interventions to improve health 
domestically and worldwide. Understanding and developing 
countermeasures against microbes that threaten our public health is 
central to NIAID's mission. NIAID will continue to fund meritorious 
basic and clinical research with the ultimate goal of translating these 
discoveries into global public health benefits.
                                 ______
                                 
              Prepared Statement of Gary H. Gibbons, M.D.

    Mr. Chairman and distinguished members of the subcommittee: 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 2014 budget of $3,098,508,000 includes an 
increase of $25,206,000 over the comparable fiscal year 2012 level of 
$3,073,302,000.
    NHLBI leads research and education programs to discover and apply 
knowledge to improve health by preventing and treating heart, lung, and 
blood diseases. It is a privilege to serve as NHLBI Director in this 
time of unprecedented opportunity in biomedical research. Today, I will 
discuss new opportunities to reduce health disparities, advance 
understanding of complex chronic diseases, and enhance clinical 
research.

                      HEALTH DISPARITIES RESEARCH

    The NHLBI portfolio includes studies of many diseases that impose 
strikingly disparate burdens on Americans from different walks of life. 
Understanding and alleviating health disparities has been a passion of 
mine throughout my career, and I am honored to lead an Institute with 
such a longstanding commitment to supporting work in that area. Many of 
you are familiar with the NHLBI's large epidemiological studies that 
focus on minority populations, including the Jackson Heart Study in 
African Americans, the Hispanic Community Health Study, the Multi-
Ethnic Study of Atherosclerosis, which includes a sizeable cohort of 
Asian Americans, and the Strong Heart study in American Indians. Our 
recent investments in genotyping of diverse cohorts promise to shed 
critical light on biological differences in disease susceptibility as 
well as the interactions between genes and environment as determinants 
of health among all Americans. We also have an outstanding record of 
including substantial numbers of minorities in our clinical research, 
particularly in studies of high blood pressure, which appears with 
great frequency and often devastating complications in African 
Americans.
    Efforts to date have yielded progress that has benefited most 
people to some extent but, unfortunately, has done little to close the 
gaps that persist between the healthiest and least healthy segments of 
society. Because health disparities are complex and are clearly 
influenced not only by genetics but also by factors such as family, 
social community, and physical environment, we believe that they offer 
an excellent model for a new ``systems'' approach to our research 
strategy. Until recently scientists have had to consider such factors 
separately; for instance, one researcher might look at basic biological 
pathways or genetic factors, while another examines lifestyle choices 
and a third considers socioeconomic influences. This piecemeal approach 
provides a limited view of how disease occurs and, more important, how 
it can be prevented or managed effectively. To revolutionize our 
understanding of health and disease, we are now developing and 
exploiting new tools that enable consideration of many factors--
biological, behavioral, environmental--together in a holistic way. 
That, I believe, is the path to future progress in preventing and pre-
empting chronic heart, lung, and blood disorders. If we can develop the 
``systems'' research model for health disparities research we can 
transform both science and medicine by applying it more broadly to 
other public health needs.

           A NEW PARADIGM FOR UNDERSTANDING COMPLEX DISEASES

    Let me give you one example of recent findings that highlight the 
value of a cross-disciplinary approach. We have known for decades that 
the foods we eat influence our risk of developing cardiovascular 
disease (CVD). Observational studies have taught us the value of so-
called heart-healthy diets that emphasize fruits, vegetables, whole 
grains, fish, and ``good'' fats such as olive oil. Nevertheless, 
controversies persist about the potential harmful effects of red meat 
consumption. Scientists still don't know why certain foods increase or 
reduce the risk of CVD.
    Recently, a provocative series of NHLBI-funded studies provided 
some important new insights into the potential link between red meat 
consumption and atherosclerotic CVD. Researchers have shown that the 
bacteria that reside in our guts and metabolize L-carnitine, a 
substance found in red meat, may be an important culprit behind CVD. 
This interaction between diet and gut microbes leads to the production 
of TMAO (trimethylamine-N-oxide), an organic compound that circulates 
in the blood and promotes the ``clogging of arteries'' by inhibiting 
the removal of cholesterol from atherosclerotic plaque.
    This and other work is dramatically enhancing our view of how the 
trillions of microbes that co-exist in and around our bodies contribute 
to both health and disease. The research perfectly illustrates a 
``systems'' approach that interactively integrates studies in mice as 
well as large-scale population science and smaller-scale human studies. 
It provides an entirely new and critical understanding of the dynamic 
interplay between the factors that predispose patients to CVD.

                      ENHANCING CLINICAL RESEARCH

    As we work to integrate our research efforts across multiple 
disciplines, we are placing particular emphasis on ensuring that our 
clinical research is robust. A major challenge is to enhance clinical 
trials, which provide critical evaluation of new preventive and 
therapeutic approaches but are, arguably, some of our most challenging 
and expensive undertakings. In recent years, the NHLBI has been 
exploring ways to make trials more efficient and more applicable to 
real-world clinical settings. Moving forward, we plan to build on past 
successes while capitalizing on new technologies and data sources, such 
as electronic medical records.
    For many years, the NHLBI has used a network model to increase the 
efficiency of clinical trials. Our networks have a strong track record 
of conducting multiple, multi-center, clinical trials using 
standardized operations and sustainable infrastructures that minimize 
the time required to start new studies. They span a wide range of 
topics, such as asthma, cardiovascular cell therapy, pediatric heart 
disease, heart failure, childhood obesity, and transfusion medicine. A 
major problem facing our healthcare system is the costly cycle of 
chronic disease care that is characterized by persistent debilitating 
symptoms, hospitalizations for acute exacerbations of the condition, 
eventual hospital discharge, and then subsequent re-hospitalizations. 
To address this clinical practice challenge, the NHLBI is supporting 
innovation in discovery science that holds promise for breaking this 
vicious cycle of chronic heart, lung, and blood disorders. In 2014, we 
will pilot a new network structure to evaluate treatment strategies for 
acute, serious lung conditions--such as exacerbations of chronic 
obstructive pulmonary disease--that require hospitalization. If the new 
model proves successful we will apply it to clinical trials of other 
chronic diseases that are treated in inpatient clinical settings.
    Another cost-effective strategy that the NHLBI has used very 
successfully is funding ancillary studies piggybacked onto trials to 
maximize return on investment. For example an NHLBI-funded clinical 
trial demonstrating that aspirin reduces the risk of heart attack also 
included ancillary studies that sought to identify new risk factors for 
CVD. These ancillary discovery science projects superimposed on the 
original clinical trial yielded strong evidence that elevated levels of 
a marker for inflammation called c-reactive protein are correlated with 
CVD events. The insights gained from the original clinical trial and 
subsequent ancillary studies have led to an innovative strategy to 
reduce CVD that targets the inflammatory process as a causative factor 
in heart attacks. Accordingly, the NHLBI recently funded the 
Cardiovascular Inflammation Reduction Trial to determine whether 
treatment with the anti-inflammation drug methotrexate, which is 
commonly prescribed for rheumatoid arthritis, reduces the risk of heart 
attacks and strokes. Taken together, these studies illustrate the 
NHLBI's ongoing efforts to enhance the efficiency and return-on-
investment of our clinical trial portfolio so that advances in the 
practice of medicine are translated into healthier lives for all 
Americans.
    We also are pursuing new opportunities to conduct trials that are 
bigger, but simpler, with clinically relevant end points that leverage 
routine medical care and existing data in electronic medical records 
and registries. By using electronic health records data from real-world 
clinical practice, we hope not only to make trials more relevant to 
clinical practice, but also to make the results more robust and 
reproducible by including hundreds of thousands of participants. In 
fiscal year 2014, the Institute will explore the use of electronic 
medical records in clinical trials through a new initiative to compare 
the ability of two data sources, electronic health records and 
traditional prospective patient-based clinical and research data, to 
answer research questions about pediatric pulmonary vascular diseases. 
We anticipate that these innovations that enhance the cost-
effectiveness of NHLBI's approach to supporting clinical research will 
yield additional new discoveries that have a dramatic impact on the 
health outcomes of patients with chronic heart, lung, and blood 
disorders.
                                 ______
                                 
              Prepared Statement of Richard J. Hodes, M.D.

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute on Aging 
(NIA) of the National Institutes of Health (NIH). The fiscal year 2014 
budget includes $1,193,370,000, which is $72,979,000 more than the 
comparable fiscal year 2012 level of $1,120,391,000.
    More than 40 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 by 2040. In less 
than 50 years, the number of ``oldest old''--people ages 85 and older--
may quadruple. As record numbers of Americans reach older age, profound 
changes will occur in our health care and social systems.
    NIA 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 
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 the issues of 
aging and old age. Finally, we support a vibrant program of basic, 
clinical, and translational research through our Intramural Research 
Program, which underwent a revision in 2013, to recognize new paradigms 
in the field of aging research and integrate laboratories and resources 
in a way that will more efficiently foster discovery.

         IMPROVING THE HEALTH AND WELL-BEING OF OLDER AMERICANS

    Life expectancy in the developed world has improved dramatically 
over the last century, and advances in public health and medicine are 
allowing people to stay healthier longer. But, since 1980, U.S. life 
expectancy, especially for women, has lagged behind other wealthy 
nations, and cross-national studies suggest that older Americans get 
sicker sooner than older Europeans. Similar disparities in health and 
longevity exist across geographical areas within the United States. NIA 
has established an initiative to identify and address the behaviors and 
social circumstances behind these differences.
    NIA-supported investigators are continuing to work to identify the 
optimal means to address the unique health needs of older individuals. 
For example, studies have shown that regular physical activity can 
improve physical performance in older people, and with the U.S. Surgeon 
General, NIA has launched its nationwide ``Go4Life'' campaign to 
motivate older Americans to engage in physical activity and exercise. 
However, definitive evidence that physical activity can prevent 
mobility disability is lacking, and NIA supports the Lifestyle 
Interventions and Independence for Elders Study to assess whether a 
specific physical activity program can prevent disability in sedentary 
older individuals.
    NIA-supported investigators are also testing interventions for 
health conditions common to old age. For example, the Centers for 
Disease Control and Prevention reports that fully half of older 
Americans have at least two chronic health conditions that compromise 
quality of life. NIA participates in a trans-NIH initiative to develop 
interventions to modify behavior and improve health outcomes among 
individuals with multiple chronic conditions. In addition, NIA supports 
research on rehabilitation from a number of acute and chronic 
conditions, including the development and pilot testing of a smart 
phone-based self-management system for older patients with heart 
failure and development of a unique biomaterial that can act as a 
temporary replacement for both bone and cartilage. Other ongoing 
studies include the ASPirin in Reducing Events in the Elderly (ASPREE) 
trial to determine whether the benefits of aspirin outweigh the risks 
in people over 70; testosterone supplementation to delay or prevent 
frailty in older men; exercise for mood, health, and cognition; and 
several interventions for menopausal symptoms.

                 THE FIGHT AGAINST ALZHEIMER'S DISEASE

    It is estimated that as many as 5 million people in the United 
States aged 65 and older currently have Alzheimer's disease (AD), and 
annual costs of care for dementia, of which Alzheimer's is the most 
common cause, have been calculated using data from the Health and 
Retirement Study at between $157 billion and $215 billion among people 
70 and older. Unless effective treatment or preventive interventions 
are identified, these numbers will rise significantly as the number of 
older Americans continues to increase. NIA has been a leader in the 
implementation of the National Alzheimer's Project Act and the 
development of the National Plan to Address Alzheimer's Disease. Recent 
initiatives have boosted support for AD research, including the NIH 
Director's allocation of an additional $50 million in fiscal year 2012 
and $40 million in fiscal year 2013 for the disease. In the fiscal year 
2014 President's budget request for NIA, $80 million of the increase 
planned for competing research project grants will be devoted to 
Alzheimer's disease projects, in response to recommendations of the 
Alzheimer's Disease Research Summit held in May 2012. The recent launch 
of the International Alzheimer's Disease Research Portfolio (IADRP), a 
publicly available database to capture the full spectrum of current AD 
research investments and resources throughout the world, will 
facilitate coordination of these efforts.
    One active and highly promising area of research is the 
identification and elucidation of risk and protective genes for AD. For 
example, a variation in TREM2, a gene involved in inflammation and 
immune response, was recently identified as a moderate risk factor for 
late-onset AD, and a variant of the BCHE gene has been associated with 
deposition of beta-amyloid in the brain--a pathologic hallmark of the 
disease. Other investigators found that in mice, ApoE-4, the best-known 
genetic risk factor for late-onset AD, is associated inflammation of 
the blood vessels that feed the brain involving a molecule called 
cyclophilin A, suggesting that cyclophilin A may be a viable drug 
target. Finally, investigators with the NIH-supported AD Genetics 
Consortium have identified a gene, ABCA7, which appears to be more 
strongly associated with AD in African Americans than in individuals of 
European ancestry. Further study is needed to confirm and extend this 
finding.
    NIH currently supports more than 35 clinical trials, including both 
pilot and large-scale trials, of a wide range of interventions to 
prevent, slow, or treat AD and/or cognitive decline; more than 40 
compounds are in preclinical development through the AD Translational 
Initiative. Funding for the groundbreaking Alzheimer's Disease 
Cooperative Study was renewed earlier this year, and several 
interventional studies are planned: a secondary prevention trial to 
test an amyloid-clearing drug in 1,000 symptom-free older volunteers 
with abnormal levels of brain amyloid accumulation; a randomized, 
controlled trial to find out if supervised aerobic exercise can 
influence cognitive decline, slow brain atrophy, or mitigate 
Alzheimer's pathology in older adults with mild cognitive impairment, a 
condition that often leads to AD; and a study to test the drug prazosin 
to help control agitation, a common symptom in AD patients.

              UNDERSTANDING AGING AT THE MOST BASIC LEVEL

    NIA initiatives on the molecular mechanisms of aging, from in-depth 
study of single cells to the broad study of organisms at the systems 
level, continue to advance our understanding of the basic underpinnings 
of the aging process. The NIH Geroscience Interest Group (GSIG) was 
formed in 2012 to accelerate and coordinate efforts to promote 
discovery on the common risks and mechanisms behind age-related 
diseases and conditions. The GSIG has planned a number of initiatives 
for coming years, including informational activities, expansion of 
current initiatives to incorporate aging-related aims, and new trans-
NIH funding initiatives. A GSIG workshop on inflammation and age-
related diseases was held in September 2012, and a larger-scale 
workshop tentatively entitled ``Geroscience: Foundations for Delaying 
Chronic Disease and Increasing Healthspan'' is planned for fall 2013.

          EMPOWERING THE NEXT GENERATION OF AGING RESEARCHERS

    The need for health care professionals and research scientists who 
specialize in the unique needs of older individuals is becoming ever 
more urgent. 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. NIA has also established a 
program targeting undergraduate students from diverse backgrounds in 
order to advance their interest in and knowledge of aging issues.
                                 ______
                                 
              Prepared Statement of Story C. Landis, Ph.D.

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute of 
Neurological Disorders and Stroke (NINDS) of the National Institutes of 
Health (NIH). The fiscal year 2014 NINDS budget of $1,642,619,000 
includes an increase of $19,275,000 over the comparable fiscal year 
2012 level of $1,623,344,000.

                    COMBATING NEUROLOGICAL DISORDERS

    The NINDS mission is to reduce the burden of neurological disorders 
through research. For stroke, research on prevention and treatment led 
to reductions of the age-adjusted death rate by 36.9 percent and of the 
actual number of deaths by 22.9 percent from 1999 to 2009.\1\
    An intensive and inclusive NINDS planning process has identified 
the highest priority research investments to continue this progress 
against stroke. Experts across disciplines agreed that stroke clinical 
trials networks could accelerate progress. In response, NINDS is 
establishing a flexible stroke clinical trials network to conduct 
prevention, treatment, and recovery trials. With shared infrastructure, 
the network will better set priorities for studies, reduce cost and 
time in start-up, and therefore significantly improve efficiency. The 
network builds on lessons from the NeuroNEXT network, which expedites 
early phase clinical trials of new treatments, especially for rare 
diseases. NeuroNEXT uses a single Institutional Review Board and 
standard site contracts, which reduce time required to start a trial by 
months. It also accommodates projects from academic investigators or 
private partners. Trials for spinal muscular atrophy (SMA) biomarkers 
and secondary progressive multiple sclerosis are under way, and 
planning has begun for clinical trials of two therapies developed by 
the NIH Therapeutics for Rare and Neglected Disease Program.
    Reducing cognitive impairment from brain vascular disease is 
another priority that emerged from planning. Stroke itself is a major 
cause of dementia. Furthermore, the 7 million U.S. stroke survivors 
have an increased likelihood of cognitive problems, and the 13 million 
people with ``silent strokes'' \2\ may also be at risk. Vascular risk 
factors are also associated with Alzheimer's disease. In fact, there is 
a spectrum from pure vascular dementia to pure Alzheimer's disease, 
with most patients having contributions from both.\3\ This month a 
scientific workshop on Alzheimer's Related Dementias, part of the 
National Alzheimer's Project Act activities, focused on vascular 
dementia.
    Traumatic Brain Injury (TBI) is the leading cause of death and 
disability in children and young adults, common among the elderly, and 
a major concern for the military and veterans. New studies will address 
two reasons why more than 30 major clinical trials of interventions for 
TBI failed to demonstrate improved outcomes: classification schemes do 
not distinguish between different types of damage in different parts of 
brain that may respond differently to interventions, and large 
variations in outcomes among medical centers confound assessment of 
interventions in clinical trials. A study of 1,000 children will 
evaluate the effectiveness of six major critical care guidelines for 
severe, pediatric TBI that lack compelling evidence. Another 
prospective, observational, multi-center study of 5,000 adults and 
children with TBI will be coordinated with studies by the European 
Union and the Canadian Institute of Health Research to enhance the 
statistical power to detect differences. The research community has 
agreed upon standards through the NINDS TBI Common Data Elements 
program that will allow meaningful comparison across studies, and the 
Department of Defense and NIH-led Federal Interagency TBI Research 
informatics system (FITBIR) provides a database for sharing 
information. NIH is also addressing TBI through the Foundation for 
NIH's Sports and Health Research Program, with support from the 
National Football League. In December a workshop focused on Chronic 
Traumatic Encephalopathy (CTE), a neurodegenerative disorder that can 
follow repetitive mild brain trauma in sports and the military. Follow-
up research solicitations are underway, and this public private 
partnership will address other key aspects of sports and health in the 
coming years.
    Epilepsy is another common disorder that affects people of all 
ages. Every 6 years since 2001, the Epilepsy Benchmarks process has 
brought NINDS, the research community, and non-governmental 
organizations together to establish research milestones and monitor 
progress. This April NINDS convened a major workshop to assess progress 
and set pathways forward. Previous Benchmarks guided investments that 
are now yielding important gene findings, advances in understanding how 
epilepsy develops, and attention to comorbidities, including Sudden 
Unexplained Death in Epilepsy (SUDEP). Future Benchmarks will focus on 
disease progression and modification, predictability of seizures and 
treatment response, and aspects of gender, ethnicity, and age (children 
and elderly), among other issues. Opportunities from other investments 
could also have a significant impact on epilepsy. The community is 
excited, for example, about advances in genetics, ``big data,'' and 
brain circuit analysis.
    Opportunities are also emerging for many other brain diseases, 
common and rare. Induced pluripotent stem cells derived from patients 
with Parkinson's disease, amyotrophic lateral sclerosis (ALS), 
Huntington's and other disorders allow laboratory testing of potential 
drugs. Biomarkers under development for Parkinson's, SMA, and other 
diseases will speed clinical testing. Brain stimulation therapies have 
proven benefit for Parkinson's disease, essential tremor, and dystonia, 
and show promise for diseases including epilepsy and Tourette syndrome. 
In research settings, brain machine interfaces enable paralyzed 
individuals to control a robotic arm and hand; development of practical 
devices is underway. Gene discoveries have led to mechanism targeted 
therapies that are now in the translational pipeline for many diseases, 
for example, muscular dystrophies, SMA, familial dysautonomia, and 
fragile X.

                           BASIC NEUROSCIENCE

    Researchers in academia and industry agree that basic science 
drives progress against disease. A few recent examples: genes 
discovered for epilepsy, ALS, and autism enable the dissection of 
underlying disease mechanisms, pointing to potential targets for 
therapy development. Research is also revealing unexpected ways that 
degeneration propagates in the brain, why acute pain can become 
chronic, and that serious disabilities in children born prematurely may 
be more reversible than expected. Science of the normal brain advanced 
this year on topics as diverse as the mechanisms of itch, how the brain 
clears waste, control of brain blood flow in infants, the influence of 
anesthetics on consciousness, and brain circuits for memory.
    NINDS relies on investigator-initiated research throughout its 
programs. Engaging the insight and ingenuity of the scientific 
community in this way is especially crucial for basic research. The 
Institute has also emphasized the importance of transparent reporting 
of research findings, stressing rigor and reproducibility. A June 2012 
NINDS workshop brought together representatives of all major 
stakeholders, which has already lead to changes within and outside the 
NIH, including policies of leading journals.\4\
    Technology can also empower investigators. Investment by the NIH 
and others, together with advances in optics, computer science, genetic 
engineering, and other disciplines, has led to promising technological 
strategies to study the activity of large numbers of brain cells and 
the intricacies of their connections. The Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative partners 
Federal agencies and private foundations in a coordinated program to 
develop and apply these emerging opportunities, including study of the 
human brain. This will ultimately revolutionize understanding of how 
networks of brain cells enable us to perceive, think, and act, and what 
goes wrong in diseases of the brain. A stellar committee of scientists 
will guide this initiative, with recommendations on first steps due 
this fall and a more complete plan the following summer. History 
suggests that the most important benefits of BRAIN will be those that 
we have not yet even imagined.
---------------------------------------------------------------------------
    \1\ ``Circulation'' 134:e6-245, 2013.
    \2\ ``Circulation'' 125:e2-e220, 2012.
    \3\ ``Neurology'' 72:368-74, 2009.
    \4\ e.g., ``Nature'' 490:187-91, 2012; ``Nature'' 496:398, 2013; 
``Nature Neuroscience'' 16:1, 2013; 16:517, 2013.
---------------------------------------------------------------------------
                                 ______
                                 
              Prepared Statement of Harold E. Varmus, M.D.

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Cancer Institute (NCI) 
of the National Institutes of Health (NIH). The fiscal year 2014 NCI 
budget of $5,125,951,000 includes an increase of $63,189,000 over the 
comparable fiscal year 2012 level of $5,062,762,000.

                   CANCER DEATHS CONTINUE TO DECLINE

    The 2013 Report to the Nation on the Status of Cancer shows that 
overall cancer death rates continued to decline in the United States 
among both men and women, among all major racial and ethnic groups, and 
for all of the most common cancer sites, including lung, colon and 
rectum, female breast, and prostate. However, death rates continued to 
increase for melanoma of the skin (among men) and for cancers of the 
liver, pancreas, and uterus. The Report also emphasizes the importance 
of human papilloma virus (HPV) infection as a cause of the growing 
number of cancers, and shows that incidence rates are increasing for 
HPV-associated oropharyngeal and anal cancers. Also noted was that HPV 
vaccination coverage remains disappointingly low, falling short of the 
U.S. Government's Healthy People 2020 target, and much lower than 
vaccination rates reported in several other countries.
    The continued decline in death rates for most cancers shows that 
our nation's investment in cancer research produces life-saving 
approaches to cancer control. However, there is still critical work to 
do, for example, in reducing tobacco exposure and obesity. Taken 
together, adverse health effects from cigarette smoking--including 
heart disease, stroke, and cancer--account for an estimated 443,000 
deaths every year in the U.S.; nearly 1 in 5 deaths that could have 
been prevented. Since tobacco is responsible for about 30 percent of 
all cancer deaths in the U.S. (approximately 174,000 preventable cancer 
deaths in 2013), NCI continues to support research into methods to 
encourage smoking cessation and to discourage initiation; behavioral 
modification; and effectiveness of tobacco control efforts. Obesity, 
another significant cause of disease and preventable death, is 
associated with heart disease, stroke, type 2 diabetes and at least 
eight types of cancers. NCI funds research on the molecular mechanisms 
of obesity and cancer, and has developed new initiatives that explore 
ways to prevent and control obesity as a cancer risk factor.

         NATIONAL CANCER INSTITUTE-SUPPORTED RESEARCH ADVANCES

    The past year has yielded significant advances across the spectrum 
of cancer research, including studies of cancer mechanisms, prevention, 
detection, and therapy. One cancer detection study showed that the 
protein fibulin-3 may be able to identify patients with mesothelioma, 
suggesting that it may be a promising biomarker for high-risk 
populations exposed to asbestos. Another study found a way to target 
mesothelin, a cell surface protein that is present in normal tissues 
but overexpressed in more than 90 percent of pancreatic cancers and 
mesotheliomas, as well as in lung and ovarian cancers. Currently, the 
NCI intramural program is conducting a Phase I study of SS1P, an 
immunotoxin that targets mesothelin and destroys cancer cells, with 
plans for a Phase II study under way.
    NCI is supporting research to identify the genetic drivers of 
cancer, and to advance adoption of precise tumor diagnosis and the 
development of targeted therapies. The two major genomics initiatives, 
involving hundreds of investigators nation-wide, are The Cancer Genome 
Atlas (TCGA) and the Therapeutically Applicable Research to Generate 
Effective Treatments (TARGET) initiative, focused on adult and 
pediatric cancers respectively. TCGA recently completed a study of lung 
squamous cell carcinoma that identified several potential therapeutic 
targets related to the initiation and progression of that disease. 
Another study examined nearly 400 endometrial (uterine) cancers and 
identified four new subtypes with several possible therapeutic targets. 
This study also found genomic similarities between endometrial and 
other cancers, including breast, ovarian, and colorectal. A TARGET 
study identified a subclass of acute lymphoblastic leukemia with high 
risk of recurrence associated with novel chromosomal translocations; 
these translocations represent exploitable therapeutic targets. Another 
TARGET study found few recurrent mutations among 240 cases of high-risk 
neuroblastoma, suggesting a limited number of targets for this 
pediatric disease.
    In 2011, one of several noteworthy achievements was FDA approval of 
a new class of drug, vemurafenib, for the treatment of metastatic 
melanoma. The drug targets mutant forms of the BRAF protein, which is 
mutated in about 60 percent of these patients, leading to inhibition of 
a key growth pathway in the tumor cell, the MAPK pathway. Although the 
drug can increase the lifespan of these patients, almost all patients 
eventually develop drug resistance and relapse. Recent observations 
from several research groups have indicated that drug resistance can 
arise by any of several mechanisms. Some resistance is attributable to 
activation of the MAPK pathway, which can result from further mutation 
of BRAF itself or changes in other genes in the MAPK pathway. In other 
cases, resistance seems to result from activation of parallel pathways. 
These findings are now leading to clinical trials testing the 
hypothesis that combining the BRAF inhibitor with drugs that have been 
shown in preclinical models to reduce development of these resistance 
mechanisms will lead to longer therapeutic responses.
    A potentially exciting therapeutic advance has come from 
immunotherapy research for B cell lymphoma being conducted at several 
institutions. The approach is to use genetic engineering to construct a 
chimeric antigen receptor (CAR) by combining parts from two different 
receptors, each with key immune functions, into one receptor that is 
then expressed by the patient's own normal T cells. Early-phase 
clinical trials with a receptor called anti-CD19 CAR, which works by 
directing T cells to the malignant B cells of the tumor, have resulted 
in several dramatic long-term responses in patients with advanced stage 
lymphoma.

                PRECISION MEDICINE--APPROACHES TO CANCER

    Incorporation of genomics into cancer research and clinical trials 
constitutes a growing portion of the Institute's research portfolio. In 
the years ahead, NCI and the entire cancer research enterprise will 
extend studies of the pathogenetic roles for specific genomic changes 
in tumors and test more interventions that are based on genetic 
profiles of tumors. There are several ways in which NCI is expanding 
its pursuit of these goals, most notably by mandating that all NCI-
sponsored clinical trials include tissue collection and genomic 
analysis. NCI is also developing new approaches that explore the 
relationship between a cancer patient's genomic data (genotype) and the 
behavior of each patient's tumor (phenotype). One such study is the 
Exceptional Responders initiative, which will begin with phenotypes--
asking why a small number of patients respond very well to a particular 
regimen, while the same treatment fails in almost all others with the 
same cancer type. To probe this phenomenon, researchers will explore 
the genomic data (genotype) to look for clues as to why some patients 
enrolled in clinical trials respond to agents that do not benefit most 
patients in the same study. Some recently reported cases provide 
dramatic evidence for how a combination of molecular factors can 
explain why patients responded so well to therapy while comparable 
patients did not.
    An approach from the opposite perspective (genotype to phenotype) 
is the ``NCI MATCH'' study, which aims to screen about 3,000 patients 
with advanced cancers in an effort to find approximately 1,000 such 
cancers with genetic mutations for which new therapies, including some 
not yet approved for use, are made available by the pharmaceutical 
industry through collaborative arrangements. This approach will provide 
a level of genomic data far beyond what would typically be available 
when genotyping is limited to one or more mutations known to be 
associated with a particular cancer type. There is a great opportunity 
for investigator-initiated research to build on information that 
emerges from this kind of novel trial, leading to yet greater 
therapeutic insight.

                             TARGETING RAS

    The Frederick National Laboratory for Cancer Research (FNLCR) is a 
federally Funded Research and Development Center (FFRDC) supported by 
NCI, providing a national resource with unique capabilities for the 
development of new technologies and the translation of basic science 
discoveries into novel agents for the prevention, diagnosis and 
treatment of cancer and AIDS. NCI is poised to launch a large-scale 
project targeting RAS, an oncogene known for decades to drive the 
development of many types of cancers and about a quarter of all cancers 
in the U.S., including more than 90 percent of pancreatic 
adenocarcinomas. However, despite that information, the cancer research 
community has failed to develop effective treatments. Now, with the 
knowledge of new chemical approaches to inhibit the RAS protein 
directly and a deeper understanding of how RAS signaling works, NCI is 
launching a large-scale project to develop therapeutic strategies 
against cancers driven by RAS through a national ``hub and spoke'' 
model with scientific leaders, core facilities and important 
technologies at the FNLCR hub, and research led by investigators at 
companies, academic institutions and the NCI intramural research 
program at the spokes.
    We find ourselves at a time of tremendous opportunity in cancer 
research, building our knowledge of the genetic changes that cause 
cancer, and finding new ways to use this information to diagnose, treat 
and even prevent cancers. The President's budget for 2014 for the 
National Cancer Institute will support studies intended to foster the 
discoveries essential for this next frontier of cancer research.
                                 ______
                                 
    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 2014 NIMH budget of $1,465,782,000 represents a decrease of 
$11,734,000 below the comparable fiscal year 2012 level of 
$1,477,516,000. In my statement, I will review the scope of mental 
disorders in the United States and their impact on public health, and I 
will outline examples of NIMH's research efforts designed to address 
this challenge.

                 PUBLIC HEALTH BURDEN OF MENTAL ILLNESS

    The National Institute of Mental Health (NIMH) is the lead Federal 
agency for research on mental and behavioral disorders, with a mission 
to transform the understanding and treatment of mental illnesses 
through basic and clinical research. The global burden of mental 
illness is enormous. An estimated 11 million American adults 
(approximately 5 percent of all adults) suffer from a seriously 
disabling mental illness each year.\1\ Mental disorders are the leading 
cause of disability in the United States and Canada, accounting for 28 
percent of all years of life lost to disability and premature mortality 
(Disability Adjusted Life Years or DALYs) for people age 15-49.\2\ The 
personal, social, and economic costs associated with these disorders 
are tremendous. A cautious estimate places the direct and indirect 
financial costs associated with mental illness in the U.S. at well over 
$300 billion annually, and it ranks as the third most costly medical 
condition in terms of overall healthcare expenditure, behind only heart 
conditions and traumatic injury.\3\ \4\ Even more concerning, the 
burden of illness for mental disorders is projected to sharply increase 
over the next 20 years.\5\
    NIMH-supported research has found that Americans with serious 
mental illness (SMI)--in which the ability to function in daily life is 
significantly impaired--die 8 years earlier than the general 
population.\6\ People with SMI experience chronic medical conditions 
and the risk factors that contribute to them more frequently and at 
earlier ages. There are low rates of prevention, detection, and 
intervention for chronic medical conditions and their risk factors 
among people with SMI, and this contributes to significant illness and 
earlier death.

                  PREDICTING AND PREVENTING PSYCHOSIS

    In the past, we viewed mental disorders as chronic conditions 
defined by their apparent symptoms, even though behavioral 
manifestations of illness are in fact the last indications--following a 
cascade of subtle brain changes--that something is wrong. We understand 
now that mental disorders are brain disorders, with specific symptoms 
rooted in abnormal patterns of brain activity. Moving forward, NIMH 
aims to support research on earlier diagnosis and quicker delivery of 
appropriate treatment, be it behavioral or pharmacological.
    The majority of people with serious mental illness (SMI)--in which 
the ability to function in daily life is significantly impaired--
experience significant delays to seeking care--nearly 2 years, on 
average.\7\ \8\ Untreated SMI, particularly psychosis, poses an 
increased risk for using potentially life-threatening, self-
administered treatments, such as legal or illicit substances, 
potentially resulting in death. When untreated psychosis is also 
accompanied by symptoms of paranoia and when it is associated with 
substance abuse, the risk of violence is increased. Importantly, the 
risk of violence is reduced with appropriate treatment.\9\ \10\ 
Moreover, people with SMI are 11 times more likely than the general 
population to be victims of violence.\11\ Therefore, NIMH has planned 
several new research initiatives, ramping up the Institute's commitment 
to early treatment in order to reduce this period of untreated 
psychosis to less than 12 weeks. These initiatives propose two 
objectives: (a) improving detection of youth and young adults at high 
risk for psychosis; and (b) reducing the duration of untreated 
psychosis in community treatment settings.

                        IMPROVING PUBLIC HEALTH

    When violence is associated with mental illness, it is most often 
self-directed. Approximately 5 percent of individuals with 
schizophrenia will die by suicide during their lifetime, a rate 50-fold 
greater than the general population.\12\ Furthermore, suicide is the 
10th leading cause of death in the United States, accounting for the 
loss of more than 38,000 American lives each year, more than double the 
number of lives lost to homicide.\13\ NIMH is spearheading several 
initiatives intended to reduce and prevent suicide, such as taking a 
lead role with The National Action Alliance for Suicide Prevention, a 
public-private partnership tasked with developing the next National 
Strategy for Suicide Prevention. Alongside the Jed Foundation, NIMH is 
co-chairing the Action Alliance's Research Task Force (RTF), which is 
developing a National Research Agenda to reduce suicide morbidity 
(attempts) and mortality (deaths) by at least 20 percent in 5 years, 
and 40 percent or more in 10 years. The RTF aims to release the Agenda 
in September 2013.
    One of the most notable and disturbing increases in suicide over 
the past decade has occurred among the Nation's returning military 
veterans. To counter this trend, NIMH has partnered with the Department 
of the Army to conduct the Army Study to Assess Risk and Resilience in 
Servicemembers (Army STARRS) Project--the largest study of mental 
health risk and resilience ever conducted among military personnel. 
Army STARRS seeks to identify factors that both protect soldiers' 
mental health and those that put a soldier's mental health at risk. The 
goal is to provide empirical evidence to help the Army develop targeted 
prevention and treatment strategies. Army STARRS has established a data 
enclave that integrates the administrative records of the 1.6 million 
soldiers who served between 2004 and 2009. In addition, Army STARRS 
includes a series of studies involving soldiers currently serving on 
active duty. Most of these studies have now finished enrolling subjects 
and the data are being analyzed.
    NIMH, along with other NIH Institutes and the Departments of 
Defense, Education, and Veterans Affairs are contributing to the 
development of the National Research Action Plan (NRAP), pursuant to 
Executive Order, ``Improving Access to Mental Health Services for 
Veterans, Service Members, and Military Families'' (http://
www.whitehouse.gov / the-press-office / 2012 / 08 / 31/executive-order-
improving-
access-mental-health-services-veterans-service). NRAP will 
strategically inform planning for future federally funded research 
related to mental health and traumatic brain injury among veterans and 
soldiers. NRAP will address post-traumatic stress disorder, depression, 
suicide prevention, and some aspects of substance abuse prevention and 
treatment.

                  THE FUTURE OF MENTAL HEALTH RESEARCH

    On April 2, President Obama proposed the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative (http://
www.nih.gov/science/brain/index.htm), a bold plan not only to transform 
our fundamental understanding of the brain, but also to revolutionize 
both our approach to brain research and our understanding of brain 
disorders. BRAIN will encourage the development of innovative 
technology necessary for monitoring the activity of millions of brain 
cells simultaneously and translate that activity into circuit diagrams 
and algorithms. This effort will advance our understanding of how the 
brain works and fails to work, and how it can be repaired.
    Research has taught us to detect diseases early and intervene 
quickly to preempt later stages of illness. This year, we will avert 
1.1 million deaths from heart disease because we have not waited for a 
heart attack to diagnose and treat coronary artery disease.\14\ Our 
best hope of reducing mortality from mental illness and other brain 
disorders will come from realizing that just like other medical 
disorders, we need to diagnose and intervene before the symptoms become 
manifest. Our investments today ensure a healthy tomorrow.
---------------------------------------------------------------------------
    \1\ Substance Abuse and Mental Health Services Administration. 
``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: Substance Abuse and Mental 
Health Services Administration, 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.
    \3\ Insel TR. Assessing the economic cost of serious mental 
illness. ``Am J Psychiatry.'' 2008 Jun;165(6):663-5.
    \4\ Soni A. ``The Five Most Costly Conditions, 1996 and 2006: 
Estimates for the U.S. Civilian Noninstitutionalized Population.'' 
Statistical Brief #248. July 2009. Agency for Healthcare Research and 
Quality, Rockville, MD.
    \5\ Bloom DE, Cafiero ET, Jane-Llopis E, Abrahams-Gessel S, Bloom 
LR, Fathima S, Feigl AB, Gaziano T, Mowafi M, Pandya A, Prettner K, 
Rosenberg L, Seligman B, Stein A, Weinstein C. ``The Global Economic 
Burden of Non-communicable Diseases.'' Geneva, Switzerland: World 
Economic Forum, 2011.
    \6\ Druss BG, Zhao L, Von Esenwein S, Morrato EH, Marcus SC. 
Understanding excess mortality in persons with mental illness: 17-year 
follow up of a nationally representative U.S. survey. ``Med Care.'' 
2011 Jun;49(6):599-604.
    \7\ Wang PS, Berglund PA, Olfson M, Kessler RC. Delays in initial 
treatment contact after first onset of a mental disorder. ``Health Serv 
Res.'' 2004 Apr;39(2):393-415.
    \8\ Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T. 
Association between duration of untreated psychosis and outcome in 
cohorts of first-episode patients. ``Arch Gen Psychiatry.'' 2005 Sep 
62:975-983.
    \9\ Swanson JW, Swartz MS, Van Dorn RA, Volavka J, Monahan J, 
Stroup TS, McEvoy JP, Wagner HR, Elbogen EB, Lieberman JA; CATIE 
investigators. Comparison of antipsychotic medication effects on 
reducing violence in people with schizophrenia. ``Br J Psychiatry.'' 
2008 Jul;193(1):37-43.
    \10\ Steadman HJ, Mulvey EP, Monahan J, Robbins PC, Appelbaum PS, 
Grisso T, Roth LH, Silver E. Violence by people discharged from acute 
psychiatric inpatient facilities and by others in the same 
neighborhoods. ``Arch Gen Psychiatry.'' 1998 May;55(5):393-401.
    \11\ Teplin, LA, McClelland, GM, Abram, KM & Weiner, DA. Crime 
victimization in adults with severe mental illness: comparison with the 
National Crime Victimization Survey. ``Arch Gen Psychiatry,'' 2005, 
62(8), 911-921.
    \12\ Hor K. & Taylor M. Suicide and schizophrenia: a systematic 
review of rates and risk factors. ``J Psychopharmacol.'' 2010;24(4S): 
81-90.
    \13\ Centers for Disease Control and Prevention, National Center 
for Injury Prevention and Control. Web-based Injury Statistics Query 
and Reporting System (WISQARS): www.cdc.gov/ncipc/wisqars accessed May 
2013.
    \14\ Vital Statistics of the United States, CDC/National Center for 
Health Statistics. (2011, August). Age-adjusted Death Rates for 
Coronary Heart Disease (CHD). National Heart Lung and Blood Institute. 
Retrieved January 23, 2013, from http://www.nhlbi.nih.gov/news/
spotlight/
success/conquering-cardiovascular-disease.html.
---------------------------------------------------------------------------
                                 ______
                                 
  Prepared Statement of Martha J. Somerman, D.D.S., Ph.D., 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 2014 NIDCR budget of $411,515,000 includes an 
increase of $1,568,000 over the comparable fiscal year 2012 level of 
$409,947,000.
    When NIDCR was established as a research home for oral health in 
the mid-20th century, it focused primarily on oral infectious diseases 
like tooth decay and periodontal disease. Today, the Institute 
maintains a diverse and productive research portfolio that extends 
beyond infections in the mouth. In keeping with its mission to improve 
the Nation's oral health, the breadth of NIDCR-funded research includes 
basic science studies aiming to understand development, maintenance, 
and regeneration of tissues of the face and head; novel preventive, 
diagnostic, and treatment approaches for oral infections and oral 
cancer; investigating the role the mouth plays as an indicator of 
overall health; and community-led studies of issues related to dental 
care.

                   REALIZING PERSONALIZED ORAL HEALTH

    Personalized health, aiming to individualize care based on a 
person's unique genetic, environmental, and clinical profile, is not 
new: dentists and physicians have long recognized variations among 
patients, and they have provided customized care based on the history, 
environmental exposure, and behavioral components that shape a person's 
health. However, new technologies offer additional strategies. For 
example, the NIDCR investment in molecular diagnostics using saliva is 
a key step toward advancing personalized care. As a diagnostic fluid, 
saliva has long been recognized to have many advantages over blood. 
These include simple, non-invasive collection; the potential for lower 
testing costs; portability; and application at or near the site of 
patient care, maximizing convenience and allowing the results to be 
available immediately to the patient. Recent progress comes from NIDCR-
supported scientists that developed a miniaturized, portable biochip 
that can analyze small volumes of saliva. During the first phase of 
this project, the researchers found promising predictive markers for 
cardiac events. Other research identified the presence, in saliva, of 
disease-related proteins and RNAs for oral cancers, Sjogren's syndrome, 
and conditions such as periodontal disease.
    Beyond supporting the development of molecular-based tools to 
individualize care, NIDCR appreciates the important role of behavior 
and environment in determining an individual's health status. As 
trusted providers in a private setting, dentists have an extraordinary 
opportunity to communicate to their patients the health risks of 
behaviors such as alcohol and tobacco use. NIDCR-funded projects are 
currently exploring how dental providers can help their patients by 
providing smoking-cessation advice.

                   PROGRESS IN ORAL DISEASES: CANCER

    The 5-year relative survival rate for oral and pharyngeal cancer is 
approximately 60 percent, which is among the lowest for all major 
cancers.\1\ This outlook is significantly worse for African Americans, 
who face a 5-year relative survival rate close to 40 percent. In 
addition to bringing behavioral science tools and expertise to bear on 
this problem, NIDCR aims to initiate and lead an NIH-wide effort in 
oral premalignancy identification and oral cancer prevention. The 
multi-pronged approach weaves together scientific advances in molecular 
profiling with clinical testing of the FDA-approved drug rapamycin for 
its effectiveness against certain cancers of the head and neck. Also, 
in fiscal year 2014 NIDCR will launch an initiative supporting research 
on a unique type of cell capable of initiating oral cancer, as 
therapies targeting these cells could potentially eliminate the 
``root'' of the cancer.
    Infection with human papillomavirus (HPV) is an increasingly 
recognized risk factor for distinct forms of oral and pharyngeal 
cancer. NIDCR remains vigilant to this rising public health concern. 
The incidence of HPV-linked oral cancers in the United States has been 
increasing at a rapid rate--by 225 percent from 1998 to 2004, and now 
37 percent of oral and pharyngeal cancers are HPV-associated 
cancers.\2\ Because the FDA-approved HPV vaccine Gardasil is effective 
against the particular strains of HPV implicated in oral cancers, NIDCR 
is supporting efforts to determine the potential benefit of this 
vaccine in preventing these terrible diseases.

                    PROGRESS IN ORAL DISEASES: PAIN

    NIDCR has a long-standing interest in the understanding and 
management of chronic pain. In 2012, the Institute launched the second 
phase of Orofacial Pain: Prospective Evaluation and Risk Assessment 
(OPPERA), the first-ever large, prospective clinical study to identify 
risk factors for temporomandibular joint disorder (TMJD). OPPERA II 
will follow more than 3,000 initially pain-free individuals for three 
to 5 years. OPPERA II will build upon OPPERA I and further explore risk 
factors and genome-wide markers for chronic TMJD as well as for several 
frequently overlapping pain conditions. Also in 2012, NIDCR partnered 
with the National Institute of Neurological Disorders and Stroke to 
host a workshop focused on identifying innovative scientific approaches 
to the study of chronic overlapping pain conditions. Together, these 
efforts are expected to have an impact not only on TMJD, but also on 
other chronic pain conditions including fibromyalgia, irritable bowel 
syndrome, chronic headache, vulvodynia, and chronic fatigue syndrome. 
In addition, NIDCR co-sponsored a meeting in 2013 with two other NIH 
Institutes to explore opportunities to utilize contemporary and 
integrative approaches in understanding TMJ structure and function, 
including novel imaging and molecular diagnostic techniques.

            SYSTEMS APPROACHES TO UNDERSTANDING ORAL HEALTH

    Oral tissues and fluids have remarkable protective roles, dependent 
on human components and those of oral bacteria. The NIH Human 
Microbiome Project (HMP) has created unprecedented opportunity to learn 
much more. NIDCR is harnessing HMP knowledge and tools to define the 
overlapping and unique roles of the oral microbiota in oral diseases 
and immune function--such as in susceptibility to autoimmune diseases 
and cancer--and in other systemic conditions like metabolic syndrome, a 
cluster of co-occurring conditions including increased blood pressure, 
blood sugar levels, body fat, and cholesterol levels that can raise the 
risk of heart disease, stroke, and diabetes. NIDCR is investing 
resources in new approaches to understand the properties of the vast 
majority (more than 80 percent) of the microbial universe in our mouths 
that cannot be grown in the laboratory. These studies will provide 
insights into interactions among microbes and with human cells, 
potentially leading to the development of novel strategies for 
prevention, diagnosis, and treatment of oral diseases.
    Genome-wide association studies, or GWAS, are another example of 
the broad utility of systems approaches for investigating oral health 
biology. GWAS methods combine human genome sequencing and high-speed 
computing, to scan the entire genome for disease triggers and factors. 
In the realm of oral health, GWAS suggest that the risk for dental 
caries arises from interplay between genetic factors, home fluoride 
exposure levels, and in some cases, taste preferences. Further analyses 
may point to common risk factors for dental caries and other conditions 
such as diabetes and cardiovascular disease. NIDCR-funded genetic 
studies of craniofacial development and birth defects have yielded 
information on the causes of cleft lip and palate and craniosynostosis, 
and this research will continue to be a focus moving forward.

                 NEW DIRECTIONS IN ORAL HEALTH RESEARCH

    Minding workforce trends and the importance of interdisciplinary 
science to health promotion, NIDCR recognizes the need for 
investigators representing a range of scientific areas to conduct 
research in dental, oral, and craniofacial health. NIDCR is 
particularly engaged with the needs and contributions of practitioners, 
whose participation in research could cut the time it takes for 
laboratory research to be applied for patients. In 2005, NIDCR launched 
the Practice-Based Research Network, or PBRN, and the second, 7-year 
phase began in April 2012. This powerful ``real world'' research 
network is recruiting practitioners in every State--with a goal of 
involving at least 5,000--to propose and perform clinical studies on 
topics important to dentistry. Because the research is conducted by 
clinicians in their own practices, dentists are more likely to accept 
and adopt the findings. The expected result is nothing short of a 
transformation of dental practice--one that will yield more 
individualized and evidence-based treatment and prevention, to the 
benefit of millions of Americans.
---------------------------------------------------------------------------
    \1\ Siegel et al., (2013) Cancer statistics, 2013. ``CA: A Cancer 
Journal for Clinicians.'' 63 (1) 11-30.
    \2\ Gillison ML et al. (2012) ``JAMA'';307,693-703; Jemal A et al. 
(2013) ``J Natl Cancer Inst.''
---------------------------------------------------------------------------
                                 ______
                                 
  Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P., Director, 
    National Institute of Diabetes and Digestive and Kidney Diseases

    Mr. Chairman and members of the committee: I am pleased to present 
the President's fiscal year 2014 Budget request for the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the 
National Institutes of Health (NIH). The fiscal year 2014 budget 
includes $1,811,786,000, which is $18,080,000 above the comparable 
fiscal year 2012 appropriation of $1,793,706,000. Complementing these 
funds is an additional $150,000,000 also available in fiscal year 2014 
from the Special Statutory Funding Program for Type 1 Diabetes 
Research. 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.

           TODAY'S BASIC SCIENCE FOR TOMORROW'S BREAKTHROUGHS

    NIDDK-supported basic science research is achieving remarkable 
advances and building the foundation for previously unimaginable 
strategies to improve health and quality of life. Among these advances, 
recent research into biological processes showed that two newly 
discovered molecules--irisin and TRPV4--regulate energy expenditure in 
mice. Irisin was shown to promote energy expenditure (calorie burning), 
and reduced obesity and type 2 diabetes. Mice genetically engineered to 
lack TRPV4 had increased energy expenditure without differences in food 
intake, physical activity, or body temperature. If these findings are 
extended to humans, administration of irisin or targeting of TRPV4 
could be potential new therapeutic approaches for obesity and type 2 
diabetes. In addition, newly identified brown fat progenitor cells and 
factors that regulate brown fat development may lead to new obesity 
therapies that coax cells in white fat tissue to burn calories faster, 
like brown fat. The microorganisms that inhabit the gastrointestinal 
tract are important factors in maintaining or tipping the balance 
between digestive health and disease. Investigators have also reported 
that early exposure to ``friendly'' microbes protects against 
inflammatory bowel disease in animal models. Investigating the 
different types of bacteria that reside in the intestines, researchers 
have discovered surprising links to diet, diversity with respect to age 
and geographic location, fatty liver disease, and antibiotic exposure. 
Scientists supported by our Institute have shown that pancreatic b 
cells can revert to an earlier developmental stage and lose their 
ability to produce insulin; thus, approaches that save cells that have 
regressed and restore them to become b cells again could be an 
effective way to treat type 2 diabetes. Other scientists have 
illuminated the complex system of regulation surrounding kidney 
fibrosis following injury, and identified potential targets for further 
strategies aimed at preventing and possibly reversing kidney fibrosis. 
For example, one molecule, called microRNA-21, was found to be highly 
elevated in two mouse models of kidney disease soon after injury but 
before fibrosis appeared. Mice engineered to lack the microRNA-21 gene 
showed diminished fibrosis in response to kidney injury. This molecule, 
which is found in humans with kidney injury, represents a potential 
target for antifibrotic therapies in kidney disease.
    NIDDK will continue support for basic research across the 
Institute's mission, to gain further insights into health and disease 
and propel new ideas for interventions. Areas of emerging opportunity 
include research on human b cells toward the goal of developing cell 
replacement therapies; genetic analyses to identify genes and gene 
regions associated with inflammatory bowel disease; identification of 
environmental triggers of type 1 diabetes in genetically susceptible 
newborns; and development of blood and urine tests to better predict 
patients who will have rapid progression of kidney disease or worsening 
of heart disease.

                   TRANSLATIONAL AND CLINICAL SCIENCE

    Through innovative design and rigorous testing of interventions--
whether in the operating room, doctor's office, or home or community 
settings--NIDDK-supported researchers are improving lives with new 
approaches to prevent, treat, and reverse diseases and disorders. For 
example, investigators have recently reported that weight loss and 
increased physical fitness slow decline in mobility in overweight or 
obese adults with type 2 diabetes. Invasive and costly tests commonly 
performed in women before surgery for stress urinary incontinence may 
not be necessary--information that women and their physicians can 
consider in planning treatment. This could result in fewer unnecessary 
procedures and a savings in healthcare costs. Additional research has 
shown that interventions to prevent type 2 diabetes in people at high 
risk for the disease are a very cost-effective way to improve their 
health and quality-of-life.
    Because many diseases within our mission disproportionately affect 
certain populations, we will also continue to seek insights and answers 
to health disparities. As just a few examples of our many clinical 
studies, Institute-supported scientists are conducting two large-scale, 
long-term observational studies of chronic kidney disease (CKD), the 
Chronic Kidney Disease in Children (CKiD) Study and the Chronic Renal 
Insufficiency Cohort (CRIC) Study, to address a wide range of 
scientific questions focused on prediction and mechanisms of CKD 
progression in both children and adults. Several efforts are 
translating CKD research into improved clinical outcomes such as 
decision support interventions to improve renal replacement therapy 
preparation. Among multifaceted efforts to meet the challenge of 
obesity is a consortium studying lifestyle interventions for overweight 
and obese pregnant women, to improve the health of both mother and 
child. The Institute continues to support clinical studies for a range 
of liver diseases including a multicenter research network planning 
trials of different treatment strategies for hepatitis B, including 
comparative effectiveness research. The MERIT-UC study investigators 
are conducting a multicenter trial to investigate the safety and 
efficacy of methotrexate (a drug also used to treat some forms of 
cancer and rheumatoid arthritis) in adult patients with active 
ulcerative colitis. The Glycemia Reduction Approaches in Diabetes: A 
Comparative Effectiveness study has as its overarching goal to 
understand the relative effectiveness of different medications in 
combination with metformin, and whether introducing them sequentially 
or initially in combination is most effective in maintaining glycemic 
goals over time in patients with type 2 diabetes. To maximize the reach 
and benefits of interventions proven successful in clinical trials, 
NIDDK will sustain support for translational research.

           RECRUITING AND RETAINING DIVERSE SCIENTIFIC TALENT

    NIDDK will continue programs to train and support researchers at 
all stages of their careers, and to ensure that we benefit from the 
best scientific minds. This year, NIDDK held its 11th annual Network of 
Minority Research Investigators workshop to encourage and facilitate 
participation of underrepresented racial and ethnic minority groups in 
the conduct of biomedical research. Several NIDDK-sponsored programs 
provide opportunities for minority students to obtain research 
experience. For example, NIDDK's Short-Term Education Program for 
Underrepresented Persons, or STEP-UP, provides research education 
grants to seven institutions to coordinate three high school and four 
undergraduate STEP-UP programs that enable students to gain summer 
research experience and training. STEP-UP and the NIH Building 
Infrastructure Leading To Diversity (BUILD) Consortium will work to 
identify resources which may be shared and to exchange lessons learned/
best practices.

  INTEGRATING SCIENCE-BASED INFORMATION INTO PRACTICE: EDUCATION AND 
                                OUTREACH

    NIDDK also will continue to support education, outreach, and 
awareness programs. In 2012, NIDDK, in collaboration with NLM, launched 
the LiverTox database--a free source of evidence-based information for 
healthcare professionals and for researchers studying liver injury 
associated with prescription and over-the-counter medications, herbal 
products, and dietary supplements. Likewise, in 2012, NIDDK 
collaborated with Home Box Office to develop ``The Weight of the 
Nation'' documentary series showing how obesity affects the Nation's 
health, and how interventions can turn the tide against obesity and its 
complications. In addition, NIDDK's National Kidney Disease Education 
Program collaborated with the American Diabetes Association's ``Live 
Empowered'' program, the National Coalition of Pastors' Spouses, and 
Chi Eta Phi Sorority, Incorporated, to kick off the first nationwide 
``Kidney Sundays'' event to raise awareness of kidney disease risk 
factors among African Americans.
    In closing, NIDDK's future research investments will be guided by 
five principles: maintain a vigorous investigator-initiated research 
portfolio; support pivotal clinical studies and trials; preserve a 
stable pool of new investigators; foster research training and 
mentoring; and disseminate science-based knowledge through education 
and outreach programs.
                                 ______
                                 
 Prepared Statement of Judith H. Greenberg, Ph.D., Director, National 
                 Institute of General Medical Sciences

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget for the National Institute of General Medical 
Sciences (NIGMS) of the National Institutes of Health (NIH). The fiscal 
year 2014 budget of $2,401,011,000 includes a decrease of $24,511,000 
below the comparable fiscal year 2012 level of $2,425,522,000.
    Basic discovery for better health is the past, present, and future 
of NIGMS. Today, amid the breakneck speed of progress in biomedical and 
information science technology, truly phenomenal opportunities for 
progress are at our doorstep.
    In one recent example of the merit of joining the biological and 
information sciences, scientists with the NIGMS-led NIH 
Pharmacogenomics Research Network (PGRN) devised a computer algorithm 
to sift through millions of reports to the U.S. Food and Drug 
Administration to predict dangerous, yet unsuspected interactions 
between medications such as those between antidepressants and a common 
blood-pressure medication. In another case, researchers with the 
Institute's flagship Protein Structure Initiative (PSI) solved the 
three-dimensional atomic structure of the molecule on the surface of 
brain cells that attaches to opioids and is centrally involved in 
pleasure, pain, addiction, depression, psychosis, and related 
conditions. By linking these conditions in molecular terms, the 
research may well lead to better, more targeted drug therapies for a 
range of brain-related conditions. A third example comes from 
investigators with the NIGMS-funded Models of Infectious Disease Agent 
Study (MIDAS) program. They showed that methicillin-resistant 
``Staphylococcus aureus'', or MRSA, infections are better prevented 
when hospitals cooperate and coordinate their infection control 
procedures. This research points to policy-related measures that could 
have a significant impact on public health.

                     FROM BENCH TO BEDSIDE AND BACK

    For several decades, NIGMS has provided a home for research 
conducted in emergency care settings. The Institute's burn and trauma 
centers have made many discoveries that have been implemented 
clinically. These include the development of artificial skin for burn 
victims, nutritional standards for the care of severely injured 
patients, and new understanding of how inflammation affects injury and 
healing in people who have experienced severe physical trauma.
    This past year, NIGMS announced the formation of the Office of 
Emergency Care Medicine (OECR). This office is the culmination of 
several years of discussions between NIH and the emergency medicine 
community, and responds to reports about the Nation's emergency medical 
system issued in 2006 by the Institute of Medicine. Although OECR does 
not have funding authority, it will provide agency-wide coordination 
toward speeding diagnosis and improving care for the full spectrum of 
conditions that require emergency treatment.
    Another compelling example of the clinical relevance of NIGMS-
supported basic research is the Developmental Genome Anatomy Project 
(DGAP), which employs a model of ``patient as laboratory.'' DGAP 
scientists identify abnormalities in the DNA of people with a disorder 
that is not well understood, and then follow up with laboratory studies 
to further probe the molecular defect in animal models. One exciting 
DGAP discovery is a prenatal diagnostics method that analyzes DNA in 
amniotic fluid using customized whole-genome sequencing.

                  BASIC DISCOVERIES FOR BETTER HEALTH

    NIGMS-supported research employs a range of non-human model 
organisms to ask and answer questions about human biology. One example 
is research to understand circadian rhythms, commonly known as the 
biological clock. The foundation of knowledge gathered over the years 
in this area of science is now coming together to help explain how 
various diseases and conditions are influenced by the time of day. 
Recent NIGMS-funded studies have shown that circadian rhythms have a 
major influence on the production of the basic units of metabolism such 
as amino acids, sugars, and fats. Researchers learned that about 60 
percent of these essential metabolites that sustain and promote cell 
health and growth are synchronized with the body's clock system. These 
findings are important because of their connection to other NIGMS-
supported research established a link between circadian rhythms and 
chronic conditions like diabetes and obesity, which involve activities 
linked to time of day including eating, sleeping, and physical 
activity. Integrating knowledge from basic metabolism and circadian 
biology has implications for managing the many conditions related to 
our biological clocks.
    Aside from their use as models for basic cell biology, genetics, 
and metabolism, bacteria are a focus of study for NIGMS-supported 
researchers in another way: the study of bacterial communities called 
biofilms. Many individual microbes do not cause disease; indeed, they 
aid in normal digestion and perform other vital roles in the body. Yet, 
when some otherwise non-harmful strains of bacteria assemble into a 
film structure, they can clog medical devices like heart valves and 
catheters. Using powerful microscopes and time-lapse imaging, NIGMS-
supported scientists watched biofilms form, as microbes joined together 
to create slimy ribbons that ensnared other bacteria as they traveled 
through narrow, fluid-filled tubes mimicking implanted medical devices. 
The researchers were surprised to learn just how fast this clogging 
occurred, and with no apparent warning. These research results could be 
used toward the development of clog-resistant medical devices.

              ENABLING TECHNOLOGY THAT ADVANCES DISCOVERY

    Technology is a key driver of progress in biomedicine. NIGMS 
considers its support of resource development a vital component of the 
Institute's investment in allowing creative scientists to uncover new 
knowledge and make breakthrough discoveries.
    One example of NIGMS-supported resource development is the NIGMS 
Biomedical Technology Research Centers program, a synergistic 
interaction of technical and biomedical expertise. These Centers 
promote the widespread and routine application of pioneering 
technologies and methods, and apply them to a broad range of basic, 
translational, and clinical research efforts. The resources--ranging 
from electron microscopes to bioinformatics platforms to mass 
spectrometers and other technologies--are used by thousands of NIH-
supported scientists each year.
    A second example is the Institute's investment in research on 
chemistry methods that can be used and re-purposed by both academia and 
industry. In one recent instance, scientists used NIGMS research funds 
to make a chemistry toolkit that can quickly and easily generate dozens 
or even hundreds of versions of a single molecule, toward the testing 
and refining of such molecules as potential drugs. This research is 
important because companies are unlikely to sponsor the development of 
broad-based resources like this. A key advantage of this new technique 
is that it simplifies complicated and potentially hazardous chemical 
reactions such that they can be automated and can be performed in a 
water-based environment without the use of harmful chemicals.

                        STRATEGY FOR THE FUTURE

    NIGMS has always planned strategically for the future, since 
biomedical research is a long-term commitment to supporting creative 
people to develop and test new ideas. Part of this process is keeping 
an eye on the evolution of biomedicine as new tools emerge and new 
disease threats come to light. In recent years, NIGMS has published 
companion strategic plans that chart the Institute's course for 
research and research training, noting the tight link between the two. 
The Institute continues to invest funds and resources toward activities 
that reflect the content of these plans. NIGMS strives for a healthy 
balance within its scientific portfolio between small projects that are 
conducted by individual scientists within their laboratories, and 
larger consortia (like the PGRN, PSI, and MIDAS) that enable 
researchers to work together on problems that call for a broader range 
of expertise, samples, and resources than can be managed reasonably and 
successfully by individual scientists.
    NIGMS is pleased that many of its research and research training 
efforts under way resonate so well with recommendations put forth last 
year by the NIH Advisory Committee to the Director on NIH's role in 
research training and in promoting a diverse biomedical workforce. 
Toward building a strong evidence base in workforce-related issues, 
NIGMS has funded grants that investigate factors contributing to gender 
and ethnic/racial disparity in workforce representation, to increase 
diversity. Emerging concepts include eliminating unconscious bias, 
career flexibility, and the value of good mentoring. This growing body 
of work will be pivotal to effecting change on a larger scale.
    NIGMS recognizes its vital role in supporting basic research for 
better health. In so doing, the Institute contributes in a sustained 
fashion to the health of the American people and to maintaining 
America's leadership role in science.
                                 ______
                                 
  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 President's budget request for the ``Eunice Kennedy Shriver'' 
National Institute of Child Health and Human Development (NICHD). The 
fiscal year 2014 budget of $1,339,360,000 includes an increase of 
$20,417,000 over the comparable fiscal year 2012 level of 
$1,318,943,000.
    This past year, NICHD celebrated its 50th anniversary. Beyond 
celebrating past accomplishments, this milestone inspired the 
Institute, along with its many stakeholders, to identify compelling 
scientific opportunities for the next decade. The Institute's future 
research must build upon its strong foundation of scientific advances, 
from better understanding of the basic mechanisms that transform cells 
into healthy and effectively functioning individuals, to clinical 
studies that improve the health and well-being of women, children, 
families, and individuals with disabilities.

                         DEVELOPMENTAL BIOLOGY

    Research in developmental biology helps to explain how individuals 
develop and the origins of various diseases and conditions. Recently, 
NICHD-funded scientists found that pregnant women with epilepsy who 
took the prescription drug topiramate during their first trimester to 
prevent seizures were at a slightly increased risk of having babies 
with cleft lip. Intramural scientists recently used next-generation 
gene sequencing techniques to discover new brain regions in an animal 
model, once thought to be inert, which appear to be active in the 
pineal gland, which controls the body's 24-hour wake-sleep cycle and is 
integral to development. Advances in genetics and systems biology will 
shed new light on human development, and provide critical underpinnings 
for emerging fields such as regenerative medicine.

              DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE

    Complex interactions among biological and external factors, 
starting before conception, can influence health across the life 
course, and even across generations. NICHD researchers discovered a 
genetic pathway common to the rapid growth of healthy fetuses and the 
uncontrolled cell division of cancer, shedding light on both normal 
development and the genetic bases of common cancers. Understanding the 
developmental origins of health and disease will benefit from 
interdisciplinary and global studies and, ultimately, can be applied to 
prevent, treat, or even reverse chronic conditions such as obesity, 
diabetes, and cognitive deterioration.

                    PREGNANCY AND PREGNANCY OUTCOMES

    Achieving a better understanding of pregnancy processes and fetal 
development can pave the way for predicting and preventing poor 
pregnancy outcomes as well as improving lifelong health for both women 
and infants. A new NICHD-funded study reported that pregnant women's 
exposure to the flu was associated with a nearly four-fold increased 
risk that their children would develop bipolar disorder in adulthood. 
This information may encourage and increase the use of prevention 
strategies, such as the flu vaccine. Another study found that women who 
develop gestational diabetes during pregnancy can greatly decrease 
their risk of developing type 2 diabetes later in life by maintaining a 
healthy diet in the years following pregnancy. Targeted areas for 
future research include obtaining further understanding of how to 
promote healthy pregnancies and unraveling the complex causes of 
stillbirth and prematurity.

                              REPRODUCTION

    Reproductive health is an essential element of personal well-being 
across the lifespan, and necessary to ensuring the health of future 
generations. NICHD-supported research found that the hormone progestin, 
often given as a first step in infertility treatment for polycystic 
ovary syndrome, unexpectedly decreased the odds of conception and 
giving birth. Discoveries such as this advance our understanding of 
what works in clinical practice and what may have unintended 
consequences and, at the same time, be used to identify potential new 
diagnostic and therapeutic targets for managing critical aspects of 
women's and men's reproductive health.

                         BEHAVIOR AND COGNITION

    Human behaviors can contribute to positive health outcomes or 
increase the risk of adverse ones. NICHD-funded researchers found that 
when the mind is at rest, the electrical signals by which brain cells 
communicate appear to travel in reverse, wiping out unimportant 
information, while sensitizing cells for future learning. NICHD 
research found that children who failed to acquire a particular math 
skill, number system knowledge, in first grade scored well behind their 
peers by seventh grade, pointing the way for targeted intervention when 
it matters most. In another study, seven-month old babies who were 
later diagnosed with autism took slightly longer to shift their gaze 
than babies who developed normally, which may provide an early clue to 
differences in their brain structure. Future basic and translational 
research that combines neuropsychological, behavioral, and social 
science perspectives will increase knowledge about the mechanisms that 
underlie typical and atypical behavior and cognition.

                     PLASTICITY AND REHABILITATION

    Plasticity, adaptive or maladaptive change at the cellular, tissue, 
organ, or system levels, is at the core of human development and 
rehabilitation. NICHD researchers have identified proteins in an animal 
model that help fuse early-stage cells and eventually develop into 
muscle cells. This finding has implications for understanding how to 
repair and rehabilitate muscle tissue and how specialized cells 
(osteoclasts) repair and maintain bones. The ongoing challenge for 
scientists will be to generate additional knowledge about the 
mechanisms of plasticity, and translate this knowledge into 
interventions that can help individuals remodel, maintain, or enhance 
functioning.

                          POPULATION DYNAMICS

    Individuals, families, and communities are all critical units, 
through which population-level factors interact with genetic and 
environmental variables, influencing individual health across the 
lifespan. An NICHD study demonstrated that the stresses of poverty 
(e.g., financial worries, inadequate child care), were shown to lead to 
impaired learning ability in children; high levels of stress hormones 
influence the developing circuitry of children's brains, impairing 
their executive functions. Another study, a landmark collaboration 
among NICHD, other NIH Institutes and Centers, Federal agencies, and 
private foundations, demonstrated that providing specialized housing 
vouchers that enabled low-income women and children to move from 
impoverished neighborhoods to those with relatively few poor residents 
reduced extreme obesity and diabetes over time. Over the next decade, 
research must continue to provide the comprehensive evidence needed for 
what works and how to scale programs at the population level, 
accounting for individual behaviors and biomedical factors, family and 
community characteristics, and social forces.

                           CONDUCT OF SCIENCE

    In the coming years, biomedical and biobehavioral researchers will 
need to work as transdisciplinary teams, manage massive amounts of 
data, and acquire new and diverse skill sets. The very breadth of 
NICHD's mission requires us to create, train, and support such teams to 
be able to fully translate our research advances into actions that 
improve the health of women, children, families, and individuals with 
disabilities.
                                 ______
                                 
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) of 
the National Institutes of Health (NIH). The fiscal year 2014 budget of 
$699,216,000 includes a decrease of $2,191,000 below the comparable 
fiscal year 2012 level of $701,407,000. 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.

                           STRATEGIC PLANNING

    ``The NEI Challenge to Identify Audacious Goals in Vision Research 
and Blindness Rehabilitation'' was a novel strategic planning 
initiative designed to identify innovative, groundbreaking long-term 
research goals. The challenge was open to anyone with an idea for a 10-
year audacious research goal including scientists, engineers, 
clinicians, and the public. NEI used a new prize competition authority, 
from the America COMPETES Reauthorization Act of 2010, to attract 
attention and received more than 500 ideas for audacious goals. A 
Federal review panel selected 10 winning entries for further 
consideration. Then, more than 200 leading scientists and clinicians 
met to further develop these ideas at the NEI Audacious Goals 
Development Meeting held in February 2013. Afterwards, NEI announced an 
audacious goal (Regenerate Neurons and Neural Connections in the Eye 
and Visual System) and two high-priority areas (Molecular Therapy for 
Eye Disease and the Intersection of Aging and Biological Mechanisms of 
Eye Disease) at the Association for Research in Vision and 
Ophthalmology meeting on May 5. NEI is now identifying the necessary 
steps to boldly attack these research endeavors over the coming decade.

                            CLINICAL TRIALS

    This month, NEI-supported investigators published results of the 
Age-Related Eye Disease Study 2 (AREDS2), a large, multi-center 
clinical trial designed to refine the antioxidant and mineral 
supplement formulation that was evaluated in the original AREDS 
clinical trial. The original Age-related Eye Disease Study (AREDS) 
established that daily doses of vitamins C and E, beta-carotene, zinc, 
and copper slows the progression to advanced age-related macular 
degeneration (AMD), the leading cause of visual impairment and legal 
blindness in older Americans. AREDS2 was undertaken for three reasons. 
First, preliminary evidence indicated that Omega-3 fatty acids might be 
beneficial. Second, beta-carotene, used in AREDS, was found to increase 
lung cancer risk in cigarette smokers. Third, it was suggested that the 
rather high zinc level in AREDS might cause minor side effects, such as 
stomach upset. AREDS2 investigators found that adding Omega-3 fatty 
acids, replacing beta-carotene with two other carotenoids, lutein and 
zeaxanthin, and lowering zinc levels maintained, but did not improve 
the effectiveness of the original formulation. Thus, changing the 
carotenoid and lowering the zinc in original AREDS formulations offers 
an equally effective alternative with fewer side effects. The AREDS2 
study results provide physicians and patients with new information 
about delaying or preventing vision loss from AMD.
    In February 2013, the FDA approved the Argus II Retinal Prosthesis 
System, a medical device capable of restoring ambulatory vision to 
those blind from retinitis pigmentosa. Argus II consists of a miniature 
video camera that is mounted on a pair of glasses. A processing unit 
worn on a belt converts images captured by the camera into electrical 
impulses that are wirelessly transmitted to a 60-electrode grid 
implanted in the eye. Users perceive the electrical impulses as 
patterns of light that produce visual information. The Argus II, 
developed by Second Sight, Inc., was made possible through more than a 
decade of clinical trial support from NEI.

                         TRANSLATIONAL RESEARCH

    Retinitis pigmentosa (RP) is a group of rare, degenerative diseases 
that result from mutations in any one of 40 genes that function in rod 
photoreceptor cells in the retina. These cells form our peripheral 
vision and allow us to see in dim and dark environments. As RP 
progresses, patients experience night blindness and severely restricted 
visual fields. For reasons that are not understood, the loss of rods 
eventually leads to the degeneration and death of cones, the 
photoreceptor cells in the central portion of the retina that allow us 
to perceive fine visual detail and color. Without central vision, it is 
impossible to perform essential tasks of daily life such as reading, 
driving, walking without assistance, or recognizing faces and objects.
    Vision researchers have long sought a therapeutic approach that can 
address multiple RP genotypes. However, current efforts with gene 
therapy address only one specific gene defect at a time. In a highly 
novel approach that could be applied to most, if not all, forms of RP, 
NEI-supported investigators genetically reprogrammed rods to become 
cone-like cells in a rodent model of RP. This approach reduced rod cell 
function but preserved cone cells. Although such a treatment would 
leave patients with limited peripheral vision and night blindness, this 
would be preferable to the added debilitating loss of central vision 
for the estimated 200,000 Americans who live with RP.
    NEI-supported investigators have developed a potential new 
treatment to prevent proliferative vitreoretinopathy (PVR) a sight-
threatening complication of retinal detachment that requires prompt 
surgical treatment. PVR occurs in about 10 percent of retinal 
detachments, resulting in permanent scarring of the retina. In this 
condition, retinal pigment epithelial (RPE) cells, which line the 
neural retina, migrate through the retinal detachment into the vitreous 
fluid where they rapidly multiply, dedifferentiate and contribute to 
the formation of an abnormal membrane on the surface of the retina. 
This membrane eventually contracts, pulling at the retina and forming a 
larger detachment. PVR causes heavy scarring of the retina and severe 
visual impairment. NEI investigators identified seven classes of 
biological growth factors and regulatory proteins that promote the 
proliferation and contraction of the RPE-derived membrane in an animal 
model of PVR. By inhibiting the expression of these biological factors, 
the investigators prevented PVR. This study provides insight into the 
causes of PVR and proof-of-concept for treating the condition.
    The cornea, the outer protective layer of the eye, is amazingly 
resilient to infection. By exposing cultured human corneal cells to 
bacteria, NEI researchers identified a class of peptides important in 
the cornea's defense against bacterial infection. Blocking these 
peptides in a rodent model led to a marked increase in corneal 
infections. Synthetic variations of these peptides effectively killed 
bacteria that lead to flesh-eating disease and strep throat, staph 
infections, diarrhea, and cystic fibrosis associated lung infections. 
The findings could lead to a powerful new class of low-cost antibiotics 
at a time when antibiotic resistance to existing agents is of growing 
concern.
                                 ______
                                 
   Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S., 
     Director, National Institute of Environmental Health Sciences

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute of 
Environmental Health Sciences (NIEHS) of the National Institutes of 
Health (NIH). The fiscal year 2014 NIEHS budget of $691,348,000 
includes an increase of $7,051,000 from the comparable fiscal year 2012 
level of $684,297,000.

                              INTRODUCTION

    In fiscally challenging times for science, NIEHS is finding 
innovative ways to maximize its investments through strategic planning, 
collaborative research, and focused translation of science. For 
example, NIEHS grantees have discovered a key mechanism by which 
dietary omega-3 fatty acids (fish oils) could reduce the growth and 
spread of cancer, which kills 580,000 Americans a year.\1\ New findings 
from the NIEHS Sister Study show that even moderate physical activity 
can reduce breast cancer risk,\2\ and that estrogen may help offset 
effects of obesity and alcohol on risk.\3\

                         COLLABORATIVE RESEARCH

    NIEHS develops and leads multi-disciplinary collaborations in areas 
such as the Gulf Oil spill, breast cancer and the environment, 
nanotechnology, bisphenol A, and science data management. In 
partnership with the Substance Abuse and Mental Health Services 
Administration, the NIEHS Gulf Long-term Follow-up (GuLF) Study of 
33,000 men and women will assess mental health trajectories, resiliency 
and coping, and mental healthcare needs of participants. NIEHS has 
invested $30 million from 2009 to date working with Federal partners 
and the Nation's leading researchers to fill data gaps and resolve 
controversies over the human health effects of exposure to low levels 
of BPA. Nearly 150 papers have resulted from this effort so far.\4\ 
Recent observational human studies \5\ show that early life exposures 
to BPA can potentially lead to diseases or health problems in adulthood 
such as prostate and breast cancer, obesity, diabetes, and 
cardiovascular, neurobehavioral, and reproductive disorders. Work of 
the Engineered Nanomaterials Grand Opportunity (Nano GO) Consortium of 
13 laboratories now provides investigators with standardized methods 
for predicting the toxicity of selected nanomaterials.\6\ \7\ NIEHS is 
a partner in the new National Consortium for Data Science that aims to 
address the challenges of collecting, sharing, and using large, diverse 
datasets. At its recent summit, genomic and data scientists drafted 
recommendations for translating genomic data into better, more 
affordable healthcare by developing new ways to collect, manage, 
analyze, and apply massive amounts of data into tools for scientific 
discovery and economic growth.

                          SCIENTIFIC ADVANCES

    NIEHS's investigator-initiated research provides critical advances 
in environmental health and basic sciences. New findings suggest that 
Vitamin D may reduce the risk of uterine fibroids,\8\ a condition that, 
according to NIH, afflicts up to 80 percent of American women, causes 
more than 200,000 hysterectomies each year, and results in direct 
health costs of $2.1 billion. A recent study points to exposure to 
polybrominated diphenyl ethers in flame retardants as a factor in 
increased risk of Parkinson's disease.\9\ A new analysis of the 
scientific literature shows that exposure to increased levels of 
particulate matter during pregnancy can lead to greater risk of low 
birth weight babies,\10\ putting them at risk of poor health in 
childhood and adulthood.
    Exposure to toxic substances in the environment accrues huge costs 
in human suffering, and results in economic costs to individuals and 
society; NIEHS-funded studies illustrate this dual burden. Each year in 
Europe, 1.8 million children suffer unsafe prenatal methylmercury 
exposures that affect brain development, mostly from fish in mothers' 
diets. Preventing such exposures could save the European Union 8 to 9 
billion euros per year in lost earning potential of these children.\11\ 
In a study of approximately 12.5 million elderly Medicare 
beneficiaries, researchers found a consistent increase in costly 
respiratory hospitalizations with increasing outdoor temperatures.\12\

                        STAKEHOLDER TRANSLATION

    Just as scientific rigor is required to generate sound research 
findings, vigorous approaches are needed to translate these findings to 
stakeholders. In 2012, NIEHS released a strategic plan that identifies 
key goals for the next 5 years that will provide the rubric for NIEHS 
to achieve its vision as a catalyst for the application of state-of-
the-art biomedical research to the most critical environmental health 
problems. NIEHS ``talks the talk'' by committing to effective research 
translation in its strategic plan, and ``walks the walk'' through 
engagement and translation activities with the American public.
    Community Forums around the United States allow the public to raise 
environmental health concerns with the NIEHS director. In November 
2012, NIEHS held its first virtual Community Forum on environmental 
exposures and childhood obesity, using social media and webcasting to 
reach 600 viewers and spark 1.5 million tweets. In a March forum in 
Seattle, residents voiced concerns about a site along the Duwamish 
River that is one of the most polluted in the U.S., as well as home to 
low-income and recent immigrants, and fishing grounds of three 
Northwest Tribes. In February, the NIEHS-led Interagency Breast Cancer 
and Environmental Research Coordinating Committee released 
``Prioritizing Prevention,'' recommendations for reducing environmental 
exposures and modifying lifestyle factors implicated in breast cancer.
    NIEHS provides critical Federal and global leadership to advance 
science on how the environment affects people's health to promote 
healthier lives.
---------------------------------------------------------------------------
    \1\ Zhang G, et al., Epoxy metabolites of docosahexaenoic acid 
(DHA) inhibit angiogenesis, tumor growth, and metastasis. Nature. April 
3, 2013. Published online at: http://www.pnas.org/content/early/2013/
04/03/1304321110.
    \2\ McCullough LE, et al., Fat or fit: the joint effects of 
physical activity, weight gain, and body size on breast cancer risk. 
Cancer. Oct. 1, 2012, 118(19):4860-8. Published online at: http://
www.ncbi.nlm.nih.gov/pubmed/22733561.
    \3\ Hong J, Holcomb VB, Kushiro K, Nunez NP. Estrogen inhibits the 
effects of obesity and alcohol on mammary tumors and fatty liver. 2011. 
Int J Oncol 39(6):1443-1453. Published online at: http://
www.ncbi.nlm.nih.gov/pubmed/21850368.
    \4\ http://www.niehs.nih.gov/research/resources/bpa-related/
index.cfm.
    \5\ Li D, et al., Occupational exposure to bisphenol-A (BPA) and 
the risk of self-reported male sexual dysfunction. Hum Reprod. 2010 
Feb;25(2):519-27. Published online at: http://www.ncbi.nlm.nih.gov/
pubmed/19906654.
    \6\ Xia T, et al., Interlaboratory Evaluation of ``In Vitro'' 
Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials: 
The NIEHS Nano GO Consortium. Environ Health Perspect. 2013 May 6. 
[Epub ahead of print] Published online at: http://www.ncbi.nlm.nih.gov/
pubmed/23649538.
    \7\ Bonner JC, et al., Interlaboratory Evaluation of Rodent 
Pulmonary Responses to Engineered Nanomaterials: The NIEHS Nano Go 
Consortium. Environ Health Perspect. 2013 May 6. [Epub ahead of print] 
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/23649427.
    \8\ Baird DD, Hill MC, Schectman JM, Hollis BW. 2013. Vitamin D and 
the risk of uterine fibroids. ``Epidemiology''; 24(3):447-453. 
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/23493030.
    \9\ Bradner JM, et al., Exposure to the polybrominated diphenyl 
ether mixture DE-71 damages the nigrostriatal dopamine system: Role of 
dopamine handling neurotoxicity. Exp Neurol 2013, 241:138-147. 
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/23287494.
    \10\ Dadvand P, et al., Maternal exposure to particulate air 
pollution and term birth weight: a multi-country evaluation of effect 
and heterogeneity. Environ Health Perspect; 2013 [Online 6 February 
2013]. Published online at: http://ehp.niehs.nih.gov/1205575/.
    \11\ Bellanger M, et al., Economic benefits of methylmercury 
exposure control in Europe: Monetary value of neurotoxicity prevention. 
Environ Health; 2013 [Online 7 January 2013]. Published online at: 
http://www.ncbi.nlm.nih.gov/pubmed/23289875.
    \12\ Anderson GB, et al., Heat-related emergency hospitalizations 
for respiratory diseases in the Medicare population. AJRCCM [In Press] 
Published on 14 March 2013 as doi: 10.1164/rrcm.201211-1969OC.
---------------------------------------------------------------------------
                                 ______
                                 
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 budget request for the National Institute of Arthritis 
and Musculoskeletal and Skin Diseases (NIAMS) of the National 
Institutes of Health (NIH). The fiscal year 2014 NIAMS budget of 
$540,993,000 includes an increase of $6,202,000 over the comparable 
fiscal year 2012 level of $534,791,000.

                              INTRODUCTION

    As the primary Federal agency for supporting medical research on 
diseases of the bones, joints, muscles, and skin, NIAMS touches the 
lives of nearly every American. The burden of these diseases is 
substantial. Arthritis limits the activities of nearly 21 million 
adults in the United States each year; medical care and lost wages 
attributable to musculoskeletal conditions cost Americans an estimated 
$950 billion annually; and skin conditions such as eczema and psoriasis 
affect more than 12 percent of people world-wide.\1\ NIAMS is 
accomplishing its mission of improving health by supporting basic and 
translational research that will impact clinical practice, by training 
the next generation of bone, joint, muscle, and skin scientists, and by 
disseminating the findings from its studies, and related health 
information, to all Americans.

               BASIC SCIENCE: THE FOUNDATION FOR TOMORROW

    Tomorrow's treatments are rooted in the basic research conducted 
today. NIAMS is committed to better understanding the molecular and 
cellular processes that contribute to health and disease. This basic 
research will serve as the foundation for new diagnostic tests, 
therapies, and prevention strategies that will improve the lives of 
those who are affected by arthritis, and musculoskeletal and skin 
conditions.
    NIAMS investigators are leveraging the Nation's investment in 
understanding the human genome and making use of its associated 
technologies. One such project is studying facioscapulohumeral muscular 
dystrophy (FSHD)--a neuromuscular disease of the face, shoulders, and 
upper arms. Building on earlier findings about DNA sequences on 
chromosome 4 that lead to FSHD, researchers discovered that a rare form 
of the disease--called FSHD2--is caused by mutations on both chromosome 
4 and chromosome 18. These results set the stage for new diagnostic 
tests and treatments for patients who have FSHD2. Moreover, the 
recognition that distant genes interact with each other may lead to 
similar discoveries in other conditions.
    NIAMS recognizes industry's important role in conducting basic 
research, developing new technologies, and commercializing federally 
supported discoveries. For this reason, NIAMS is offering grants to 
eligible small businesses for development of biomarkers or therapies 
for rare musculoskeletal, rheumatic, or skin diseases.

           TRANSLATIONAL SCIENCE: BRIDGING BENCH AND BEDSIDE

    NIAMS basic research can only improve public health when the 
understanding it generates is translated into new and improved 
treatments and preventive strategies. Recent insights into the 
molecular mechanisms of cell processes are already suggesting 
treatments. NIAMS researchers at the NIH Clinical Center launched a 
small clinical trial after experiments into the cause of neonatal-onset 
multisystem inflammatory disease (NOMID) revealed that it may be 
corrected with the adult rheumatoid arthritis (RA) drug anakinra. The 
children participating in the trial, who had been ill for years, 
improved within days of receiving the drug. Their rashes disappeared, 
their eye problems resolved, and their hearing improved or stopped 
worsening. The investigators then initiated a 5-year study, which led 
to U.S. Food and Drug Administration (FDA) approval of anakinra for 
pediatric NOMID patients earlier this year.
    NIAMS-funded basic research also contributed to the recent FDA 
approval of a new treatment for RA. The drug, tofacitinib, targets a 
protein discovered at NIH in 1993. Following many years of 
collaboration between NIH and private industry, tofacitinib became the 
first drug approved in more than a decade that can be taken as a pill, 
rather than an injection, to slow or halt RA joint damage. It provides 
an option for adults with moderately to severely active RA who do not 
respond well to the standard therapy for the disease--methotrexate.
    In addition to helping patients by supporting basic research and 
developing new treatments, NIAMS facilitates work that guides 
clinicians in the use of existing therapies. NIAMS funding assisted a 
national consortium of pediatric rheumatologists establish treatment 
recommendations for newly diagnosed juvenile idiopathic arthritis 
patients, and for children who develop kidney inflammation due to 
lupus. These recommendations are guiding patient care today and can be 
integrated into future effectiveness and toxicity studies as therapies 
are developed.
    Other work may help clinicians predict which scleroderma patients 
will respond to the drug mycophenolate mofetile (MMF), one of the 
standard therapies for this disorder. A small clinical trial built on 
findings about the molecular causes of scleroderma revealed a 
connection between gene expression patterns in patients' skin biopsies 
and their responses to MMF. If an ongoing study confirms this genetic 
biomarker's predictive value, countless patients might be spared 
needless exposure to MMF and could begin receiving other drugs before 
their disease progresses.
    NIAMS-supported research also is contributing to knowledge about 
dietary and behavioral changes that can prevent common public health 
challenges. Poor nutritional habits increase older Americans' risk of 
metabolic acidosis, a condition that occurs when the body produces too 
much acid or the kidneys fail to remove excess acid from the blood. 
Because bone is a reservoir for alkaline salts (e.g., calcium 
phosphate), it can lose minerals and weaken in an effort to maintain a 
healthy acid-base balance. Findings from an NIAMS-funded clinical trial 
revealed that the dietary supplement potassium citrate improves the 
acid-base equilibrium of people's blood, their calcium balance, and 
markers of skeletal health. This supports the hypothesis that potassium 
citrate can slow or prevent bone loss that occurs with age. If future 
studies confirm the results, potassium citrate could become a safe and 
easily administered intervention for patients who have, or are at risk 
of, osteoporosis and related fractures.
    NIAMS research findings are assisting healthcare providers and 
patients select among treatment options. Many adults have debilitating 
knee pain due to a tear in the meniscus, a cushion-like tissue that 
absorbs impact. Although meniscal tears can be treated with physical 
therapy or surgery, it was unclear which intervention was best until a 
recent paper showed that most patients benefited equally from either 
option over time. Those in the physical therapy group improved less 
quickly, however, and about one-third resorted to surgery because 
physical therapy did not provide adequate relief.

                ENSURING A DIVERSE SCIENTIFIC WORKFORCE

    NIAMS is committed to developing and retaining a diverse and 
collaborative scientific workforce. Planning discussions in fiscal year 
2012 that included investigators, health professionals, and patients 
identified the transition from mentored research to full independence 
as a vulnerable period in clinician-scientists' careers. In fiscal year 
2013, NIAMS met with grantees nearing the end of their clinical or 
patient-oriented research career development awards to learn about the 
challenges they and their peers are facing. NIAMS plans for fiscal year 
2014 include a similar effort, with a long-term goal of identifying 
ways to better support early-stage investigators' transition to 
research independence.

            SHARING HEALTH INFORMATION AND RESEARCH PROGRESS

    The Internet and other electronic communication platforms have 
emerged as valuable tools for disseminating health information. An 
increasing number of visitors are accessing the NIAMS Web site from 
mobile devices, and current trends indicate that mobile traffic to Web 
sites may overtake desktop traffic as soon as 2015. In response, NIAMS 
began providing its health information in a mobile device friendly 
format in fiscal year 2013. NIAMS will continue to assess and adapt to 
new technologies and tools to provide research updates and health 
information to the widest possible audience.
---------------------------------------------------------------------------
    \1\ Cheng YJ, et al. Prevalence of doctor-diagnosed arthritis and 
arthritis-attributable activity limitation--United States, 2007-2009. 
MMWR 2010;59(39):1261-1265.
    U.S. Department of Health and Human Services, Agency for Healthcare 
Research and Quality, Medical Expenditures Panel Survey, 1996-2006. 
Data analyzed and modeled by Edward H. Yelin, PhD, Institute for Health 
Policy Studies, University of California, San Francisco, San Francisco, 
CA, as cited in www.boneandjointburden.org/highlights/FactsinBrief.pdf, 
accessed March 27, 2013.
    Vos T, et al. Years lived with disability (YLDs) for 1160 sequelae 
of 289 diseases and injuries 1990-2010: a systematic analysis for the 
Global Burden of Disease Study 2010. Lancet. 2012 Dec 
15;380(9859):2163-96. doi: 10.1016/S0140-6736(12)61729-2.
---------------------------------------------------------------------------
                                 ______
                                 
  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 committee: 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 2014 NIDCD budget of $422,936,000 
includes an increase of $7,436,000 over the comparable fiscal year 2012 
appropriation of $415,500,000.
    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.

           RESEARCHERS RESTORE HEARING IN NOISE-DEAFENED MICE

    Our ability to hear relies on sensory hair cells in the inner ear. 
The hairs on these specialized cells convert sound vibrations into 
electrical signals, which travel to the brain by way of the auditory 
nerve. When hair cells are damaged--by disease, injury, or aging--a 
person experiences hearing loss, and mammals cannot regenerate these 
lost hair cells.
    Researchers supported by NIDCD have shown for the first time that a 
drug can be used to grow sensory hair cells in the inner ear. They 
injected a drug into the cochlea (a spiral shaped organ in the inner 
ear that shelters hair cells) of mice made deaf by exposure to loud 
noise. The drug blocked a cell-signaling system known to keep stem 
cells in the inner ear from turning into hair cells. By blocking that 
particular pathway, the drug encouraged cells supporting and 
surrounding the hair cells to turn into new hair cells, which led to a 
small improvement in the mice's hearing.
    This is the first study to show that scientists can use a drug to 
restore partial hearing in a mouse with noise-induced hearing loss. 
Scientists now hope to develop similar treatments to reverse hearing 
loss in humans, especially among the estimated 36 million adult 
Americans who report hearing loss.

          NOVEL APPROACHES OF INNER EAR REGENERATIVE THERAPIES

    Although research to determine ways to regenerate inner ear hair 
cells is under way, there remains a lack of potential treatments to 
restore lost mammalian hair cell function. Research is needed to 
identify and facilitate important molecular switches and regulators 
that initiate and sustain mammalian hair cell repair.
    NIDCD places a high priority in research that focuses on 
regenerative medicine. For example, the Institute is planning a 
research initiative for fiscal year 2014 with the goal of developing 
hair cell regeneration strategies. NIDCD held a workshop, in September 
2011, to identify opportunities to induce regeneration in the inner 
ear. As a result of this workshop, NIDCD issued a Funding Opportunity 
Announcement to encourage innovative and novel approaches to inner ear 
regenerative therapies research. The ultimate goal of the research is 
to identify and ``turn on'' important molecular switches and regulators 
to enable mammals to regenerate and repair their own inner ear hair 
cells. This research may result in therapies that will provide hope of 
future treatments for those who have lost hearing due to aging, injury, 
or noise exposure, including military veterans returning from active 
duty.
    Another purpose of the initiative is to attract and support NIH-
defined basic and clinical early-stage investigators (ESIs) to the area 
of biological repair of mammalian inner ear hair cells. NIDCD is 
especially interested in ESIs who bring new, innovative approaches, and 
strategies from scientific fields minimally represented in the NIDCD 
portfolio, such as tissue fabrication, biomaterials, and regenerative 
medicine. By supporting ESIs from other scientific areas, this 
initiative will encourage diversified approaches and an increased 
number of investigators focused on regenerative therapies in the inner 
ear.

RESEARCHERS IDENTIFY GENE LINKED TO PROGRESSIVE HEARING LOSS FROM NOISE 
                               AND AGING

    An international team of scientists funded by NIDCD has identified 
the first gene in humans and mouse models that is associated with both 
noise-induced and age-related hearing loss. The gene, P2X2, appears to 
be crucial for the preservation of life-long normal hearing and for 
protection from exposure to loud noise. P2X2 is associated with the 
human gene locus DFNA41, a form of hearing loss that typically begins 
early in life (around 12-20 years of age), and progresses with age. 
High-frequency tinnitus (high-pitched ringing in the ears) often 
accompanies hearing loss associated with DFNA41.
    The research team discovered that the P2X2 gene mutation found in 
DFNA41 results in defects in sensory hair cells in the inner ear, which 
eventually lead to ongoing hearing loss. The study establishes, at the 
cellular and molecular levels, that the function of this ion channel, 
previously known to be involved in sensory signaling of pain, has a 
major impact on noise-induced and age-related hearing loss.
    These findings demonstrate the importance of genetic approaches to 
uncover the underlying mechanisms that contribute to hearing loss, 
either as a result of age or chronic exposure to noise. Importantly, 
identifying the P2X2 mutation may provide scientists with a way to 
develop targeted treatments for progressing hearing loss in humans with 
DFNA41, and may be applicable to the treatment of noise-induced and 
age-related hearing loss in the broader population.

   NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS 
  SUPPORTS RESEARCH TO DEVELOP A VACCINE AGAINST AN EMERGING TYPE OF 
                        CHILDHOOD EAR INFECTION

    Ear infections during childhood are of great concern to NIDCD, 
because they not only cause pain and suffering, but they also interfere 
with a child's ability to hear properly during a critical period of 
language development. Since 2000, childhood vaccines have prevented 
many ear infections caused by two strains of bacteria--``Haemophilus 
influenzae and pneumococcus''. However, doctors are now seeing an 
increase in the number of ear infections caused by another strain of 
bacteria, called ``Moraxella catarrhalis (M. catarrhalis)''.
    NIDCD-supported scientists are working to understand how this 
bacterium infects humans and avoids destruction by the immune system. 
They hope to identify a particular structure (called an antigen) that 
is very similar among all strains of ``M. catarrhalis'', so that a 
vaccine based on a single antigen will protect against as many strains 
of the bacterium as possible.
    The research team is using bioinformatics to predict which ``M. 
catarrhalis'' proteins are likely to be found on the surface, to make 
an attractive antigen target. They are using gene chips to identify 
which genes are identical or similar among multiple strains of the 
bacterium, and then testing these in petri dishes and in animal models. 
The scientists are now testing several promising vaccine antigens 
against ``M. catarrhalis'', and hope that a new vaccine could be ready 
for human testing in a few years.
                                 ______
                                 
    Prepared Statement of Nora D. Volkow, M.D., Director, National 
                        Institute on Drug Abuse

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute on Drug Abuse 
(NIDA) of the National Institutes of Health (NIH). The fiscal year 2014 
budget of $1,071,612,000 includes an increase of $20,202,000 over the 
comparable fiscal year 2012 level of $1,051,410,000.
    The individual and societal impact of both licit and illicit 
substance abuse in America is incalculable, not to mention the 
associated economic cost, estimated at well over half a trillion 
dollars a year in healthcare, crime-related, and productivity losses. 
The current landscape of the problem reveals both new and recurrent 
trends. Prescription drug abuse remains at high levels in all age 
groups, causing thousands of needless overdose deaths each year. New 
synthetic drugs, like ``bath salts'' and synthetic marijuana 
(``spice''), are sending many teens and young adults to emergency 
rooms. And as cultural changes promote greater acceptance of the use of 
marijuana, more teens report using it and fewer perceive its real 
risks. This, despite new research showing that early onset of marijuana 
use can disrupt learning circuitry and lower IQ.
    NIDA supports a broad research agenda that leverages the full 
potential of genetic/epigenetic, psychosocial, neuroimaging, 
pharmacological, health services, and epidemiological studies in order 
to reduce the burden of drug abuse and addiction. In the context of the 
current prescription drug abuse epidemic, for example, NIDA is 
harnessing the translational power of a multidisciplinary addiction 
science to: (1) identify the major factors that modulate risk; (2) 
develop universal, broad-based prevention and treatment models 
involving individuals, their families, schools, and communities; (3) 
develop pain medications with little or no abuse potential (for 
example, a new opioid medication that must pass through the digestive 
system to become active, preventing its abuse via non-oral routes); and 
(4) promoting physician education to both improve pain treatment and 
minimize drug abuse. NIDA also supports research to make the most of 
new opportunities and therapeutics, including healthcare reform 
legislation that stands to extend effective interventions to under-
served populations, including people with substance use disorders.

                           NOVEL THERAPEUTICS

    To help those already suffering from addiction, we must expand our 
treatment toolkit. NIDA is optimally positioned to parlay research 
findings into new medication targets and promising compounds for 
pharmaceutical company investment or partnerships. Strategies now being 
tested include recruiting the body's immune system to attack and 
destroy drug molecules before they can enter the brain. This is being 
tried against nicotine, heroin, and stimulant drugs such as cocaine and 
methamphetamine, for which no medications are yet available. A related 
strategy involves delivery of an enzyme that has been molecularly 
engineered to rapidly destroy cocaine in the blood, currently in a 
phase II clinical trial. Combining existing medications is another 
promising approach, which has proven successful for a number of 
diseases (e.g., cancer and HIV/AIDS) but has not been exploited for 
treating addictive disorders. NIDA also continues to use its National 
Drug Abuse Treatment Clinical Trials Network (CTN) as a community-based 
platform to test new therapeutic interventions. For example, the CTN is 
testing an FDA-approved anxiety medication, buspirone, for its safety 
and efficacy in preventing relapse to cocaine use.

                       WIDENING THE SCOPE OF CARE

    Even effective interventions are not useful if they fail to reach 
the people who need them. Implementation research and inclusiveness of 
diverse populations in clinical trials are thus vital components of 
NIDA's research agenda to close the vast treatment gap. One example is 
research that pertains to the integration of substance abuse screening, 
brief intervention, and referral to treatment (SBIRT) into routine 
medical care and evaluation of the impact of such an approach in 
clinical outcomes of patients. Importantly, our goals in this context 
dovetail those of the Affordable Care Act, which promises to expand the 
scope of care and treat more patients suffering from substance use 
disorders. Another critical setting is the criminal justice system, 
where NIDA has long supported research to better deliver evidence-based 
treatment. Now, this focus extends to youth in the juvenile justice 
system, virtually all of whom could benefit from prevention or 
treatment interventions for drug abuse.
    Improving drug abuse prevention and treatment services also helps 
ameliorate other health consequences of abuse, including infectious 
diseases like HIV and hepatitis C virus (HCV) that can readily spread 
through the sharing of needles and other injection drug use equipment. 
One of the many translational initiatives spearheaded by NIDA is the 
``Seek, Test, and Treat'' (and ``Retain'') strategy, aimed at 
evaluating the impact of expanding highly active antiretroviral therapy 
(HAART) coverage in criminal justice and other at-risk populations 
through aggressive outreach, early entry into HIV treatment, and 
follow-up in the community. There is accumulating evidence that early 
treatment with HAART reduces new HIV diagnoses, deaths, and HIV 
prevalence, suggesting that ``Treatment as Prevention'' should be 
implemented as soon and as widely as possible.

                      NEW SCIENTIFIC OPPORTUNITIES

    By taking full advantage of continuous developments in a wide range 
of scientific disciplines, NIDA is positioned to make significant 
advances in averting and treating addictive disorders. For example, we 
can now affordably sequence full individual genomes to identify rare 
genetic variations that influence addiction and responses to treatment, 
increasing not just our basic understanding of addiction but also 
paving the way for personalized treatments. Through the rapidly 
developing field of ``epigenetics'', we can determine the lasting 
impact of environmental variables like early stress or drug exposure on 
gene expression linked to later drug use. Another powerful new tool 
called ``optogenetics'', which allows us to activate (or deactivate) 
specific brain cells and networks, has enabled NIDA researchers to link 
compulsive cocaine-seeking in rats to deficits in the prefrontal cortex 
that were reversed by activating the affected brain regions. Clinical 
trials will soon test whether noninvasive (magnetic) stimulation can 
modify brain activity and reduce compulsive drug-seeking and craving in 
human drug users. Meanwhile, advanced imaging techniques are allowing 
us to ask questions about brain structure and function that were 
unimaginable just a few years back.
    Yet even with these new technologies, the underlying causes of most 
neurological and psychiatric conditions remain poorly understood, due 
to the human brain's incredible complexity. NIDA is one of the key 
participants in an exciting new NIH initiative to conquer this major 
frontier. Brain Research through Advancing Innovative 
Neurotechnologies, or BRAIN, will produce a revolutionary new dynamic 
picture of the brain, showing how individual cells and complex neural 
circuits interact in healthy individuals, and in those with brain 
disorders.
    To better capitalize on synergies in addiction science, NIDA, the 
National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the 
National Cancer Institute (NCI) have formed a consortium, the 
Collaborative Research on Addiction at NIH (CRAN), which will pool 
resources and expertise to address unmet research opportunities and 
public health needs. Among these, the study of ``comorbidities'' is 
poised to benefit. NIDA, NIAAA, and the National Center for 
Complementary and Alternative Medicine, in collaboration with the 
Department of Defense, recently issued a call for research on 
interventions to prevent comorbid alcohol and other drug abuse in U.S. 
military personnel, veterans, and their families. NIAAA and NIDA also 
issued a call for research on mechanisms of alcohol and nicotine co-
addiction.
    The accelerating pace of science is rapidly outstripping our 
capacity to use what we collect. ``Big Data'' requires a significant 
repositioning in who we train and how we can best identify and exploit 
emerging scientific opportunities. We will need to build a workforce 
that includes people skilled in non-biomedical fields, such as 
informatics, computational science, mathematics, and engineering. 
Training the next generation of scientists to be able to understand the 
possibilities and complexities of what they will be dealing with is a 
daunting but exciting challenge as we go forward.
    In closing, we know much more about the causes and treatment of 
substance use disorders than ever before. Yet obstacles such as the 
lingering stigma attached to diseases of addiction continue to hamper 
our ability to recognize and care for those afflicted. NIDA remains 
committed to tackle these and other challenges, taking advantage of 
unprecedented scientific opportunities to transform how we prevent and 
treat substance abuse and related health consequences in this country.
                                 ______
                                 
   Prepared Statement of Kenneth R. Warren, Ph.D., Acting Director, 
           National Institute on Alcohol Abuse and Alcoholism

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute on Alcohol 
Abuse and Alcoholism (NIAAA) of the National Institutes of Health 
(NIH). The fiscal year 2014 NIAAA budget request of $463,848,000 
reflects an increase of $5,183,000 over the comparable fiscal year 2012 
level of $458,665,000.

                          SCOPE OF THE PROBLEM

    According to the Centers for Disease Control and Prevention, 
excessive alcohol use cost the U.S. an estimated $223.5 billion in 
2006; it also takes a tremendous toll on individuals and their 
families. Alcohol affects individuals across the lifespan, from the 
developing fetus to the elderly. Each of you likely knows someone 
affected by alcohol problems.

      NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM RESEARCH

    To reduce the considerable burden of illness associated with 
alcohol misuse, NIAAA is working to prevent the onset and escalation of 
drinking during childhood and adolescence and intervene with problem 
alcohol use at all ages. A substantial portion of NIAAA's research 
portfolio focuses on the underlying mechanisms, prevention, and 
treatment of alcohol dependence. The remainder is allocated to studies 
on the consequences of alcohol use, including: health benefits 
associated with moderate drinking; adverse effects resulting from 
alcohol misuse such as fetal alcohol spectrum disorders (FASD), effects 
on the developing adolescent brain, and tissue and organ damage; and 
policy research to reduce harms both to drinkers and those around them.

                         FUNCTIONAL INTEGRATION

    NIAAA has embraced the decision of the NIH Director to pursue a 
functional integration of addictions research, which provides a 
framework for NIAAA, the National Institute on Drug Abuse (NIDA), the 
National Cancer Institute (NCI), as well as other Institutes and 
Centers (ICs), to enhance and expand collaborations and identify 
synergistic research opportunities to advance addictions science. Now 
referred to as the Collaborative Research on Addictions at NIH (CRAN), 
this new venture will support a variety of activities. Importantly, 
while advancing addictions research, a functional integration maintains 
the unique research contributions of each IC.
    Prior to the official launch of CRAN, NIAAA, and NIDA implemented a 
number of changes to improve integration between the two ICs and 
initiated additional joint funding opportunity announcements (FOA). One 
joint FOA focuses on research to prevent alcohol and other drug abuse 
in active military personnel, veterans and their families. Going 
forward, CRAN will explore cross-cutting research opportunities such as 
studies on individuals who suffer from addiction to multiple 
substances--40 percent of individuals who have a past year addiction to 
illicit drugs and/or abuse prescription drugs also have past year 
alcohol abuse or dependence, and 16 percent of individuals with past 
year alcohol abuse or dependence have a past year drug addiction. CRAN 
will also support efforts to identify mechanisms that underlie tobacco, 
alcohol and/or other drug addiction, recognizing that while some 
mechanisms may be common to more than one substance, others will be 
unique. Expanding studies to address multiple substances when feasible 
and appropriate will enhance our ability to treat multi-substance co-
morbidities in an efficient and cost-effective manner. Funding 
opportunities under CRAN will begin in fiscal year 2014 with two 
initiatives; the first will expand existing projects to be more 
integrative and/or collaborative, the second will focus on mobile 
technologies and social media for interventions for substance abuse.

 NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM'S UNIQUE RESEARCH 
                                 FOCUS

    NIAAA also has a robust research program outside of CRAN. Studies 
exploring pharmacological, behavioral and policy interventions to 
reduce acute and chronic consequences of alcohol misuse are a major 
component of NIAAA's portfolio. Medications development is an active 
area of study, both for the treatment of alcohol dependence and for the 
treatment of consequences of chronic alcohol misuse such as alcohol-
induced liver disease. NIAAA's Clinical Investigations Group (NCIG) has 
streamlined the process for phase 2 clinical testing of potential 
compounds for alcohol dependence and has established an active 
collaboration with pharmaceutical companies. In a recent NCIG-led 
study, the smoking-cessation medication varenicline (Chantix) 
significantly reduced alcohol consumption and craving among people who 
are alcohol-dependent. Varenicline's effects were comparable to those 
seen in studies of naltrexone and acamprosate, two of the medications 
already approved by the U.S. Food and Drug Administration (FDA) for the 
treatment of alcohol dependence. If varenicline receives FDA approval 
for treatment of alcohol dependence, it could significantly expand 
treatment options. Personalizing treatment also continues to be a goal, 
and studies showing links between an individual's genetic make-up and 
treatment efficacy for various medications suggest that goal is within 
reach. Relapse, however, is still common and a focus of NIAAA research. 
A recent study showed that distinct patterns of brain activity are 
linked to a higher rate of relapse among patients in early recovery. 
These patterns may be useful for identifying patients at greatest risk 
for relapse.
    The link between stress and alcohol-related problems is an 
important area of investigation. While a number of studies have focused 
on how stress contributes to the development of alcohol-related 
problems and relapse, a recent line of investigation is exploring how 
chronic alcohol use might increase vulnerability of the brain to the 
development of stress-related disorders. A study in mice suggests that 
chronic alcohol use may increase the risk for post-traumatic stress 
disorder (PTSD) by altering neural circuits that normally enable the 
brain to extinguish fear following a traumatic event.
    NIAAA also continues to support medications development for the 
treatment of alcoholic liver disease (ALD), one of the most serious 
medical consequences of alcohol dependence, and continues to seek 
biomarkers for alcoholic liver damage. Scientists are gaining an 
appreciation for the interconnectedness of systems within the human 
body. NIAAA uses a systems biology approach to investigate how 
pathological changes in one organ as a result of alcohol exposure can 
also result in physiological aberrations in another. Basic research 
using animal models is also important to better understand the 
mechanisms underlying ALD; however, many of the current models do not 
evoke the full range of symptoms or are expensive and technically 
difficult. A new mouse model of alcohol drinking and disease was 
developed which more closely approximates ALD in humans and may also be 
useful to study alcohol damage of other organs.
    The developing embryo/fetus is uniquely vulnerable to the effects 
of alcohol; prenatal alcohol exposure is a significant contributor to 
neurodevelopmental disorders in children. Understanding the mechanisms 
leading to the neurodegeneration that underlies development of FASD is 
a critical step in developing treatments. A recent study provides 
evidence that endocannabinoids and their receptors in the brain play a 
role in the development of FASD.
    Policy research is another important component of NIAAA's 
portfolio. Data from NIAAA-supported studies will help inform local 
decisions such as the implementation of policy measures on college 
campuses to reduce alcohol poisonings. In addition, research findings 
play an important role in national issues such as the debate over the 
legal limit for blood alcohol content for operation of a motor vehicle, 
as policy-makers work to find a balance between increased alcohol 
restrictions and public safety. Screening and brief intervention for 
harmful alcohol use have been a major focus of NIAAA research for 
several decades. Based on this research, the U.S. Preventive Services 
Task Force (USPSTF) recently recommended that clinicians screen adults 
for alcohol misuse and provide persons engaged in risky or hazardous 
drinking with brief interventions. The USPSTF did not endorse screening 
for adolescents citing insufficient evidence. To increase this evidence 
base, NIAAA is supporting six studies to evaluate its youth alcohol 
screening guide in a variety of settings as a predictor of alcohol 
risk, alcohol use, and alcohol problems, and as an initial screen for 
other behavioral health problems such as drug use or smoking.
    In summary, NIAAA is enthusiastic about opportunities to expand 
research to improve the lives of Americans struggling with addiction to 
alcohol and other substances through the newly created CRAN. At the 
same time, NIAAA continues to focus on reducing the significant burden 
of illness associated with alcohol misuse.
                                 ______
                                 
  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 budget request for the National Institute of Nursing 
Research (NINR) of the National Institutes of Health (NIH). The fiscal 
year 2014 NINR budget of $146,244,000 includes an increase of 
$1,744,000 over the comparable fiscal year 2012 level of $144,500,000.
    The mission of NINR is to promote and improve the health of 
individuals, families, communities, and populations. The Institute does 
so by supporting and conducting clinical and basic research to build 
the scientific foundation for clinical practice, prevent disease and 
disability, manage and eliminate symptoms of illness, improve 
palliative and end of life care, and train the next generation of nurse 
scientists. NINR-supported investigators contribute to developing the 
evidence base for science-driven practice through innovative treatment 
and behavioral research. Today, I offer a brief overview of NINR's 
investment and progress in six key areas and provide examples of how 
the research we support improves quality of life.

           SYMPTOM MANAGEMENT IN MULTIPLE CHRONIC CONDITIONS

    Due to the large aging population with longer life expectancies, 
and treatment advances for formerly fatal diseases, over one in four 
Americans are living with multiple chronic conditions (MCC) and their 
associated adverse symptoms. To address these symptoms and improve 
quality of life, NINR currently supports five Centers of Excellence in 
symptom science that explore pain, sleep disturbance, and the effects 
of chronic illness on neurocognitive functioning. A recent NINR-
supported study found an association between an anti-inflammatory 
protein and a symptom cluster, including pain, fatigue, and sleep 
disturbance, opening the door to potential therapeutics development to 
alleviate these symptoms.

                  FAMILY AND COMMUNITY-BASED RESEARCH

    The family and community-based approach to clinical and 
translational research is intrinsic to nursing science and NINR. Child 
behavioral issues can create problems that negatively affect learning 
and peer relationships. NINR-supported studies that developed and 
tested the Chicago Parent Program (CPP), a high-quality, cost-
effective, early childcare program for low-income communities that 
promotes positive parenting behaviors and reduces risky behaviors in 
children and their families. The CPP was adapted and disseminated to 
Chicago Head Start sites, where it was well-received in the community. 
The researchers reported improvements in parenting skills and child 
behavior. Based on these results, CPP-derived interventions have been 
implemented in diverse settings across the U.S., such as the Mayo 
Clinic, the Harlem Children's Zone, Johns Hopkins Bayview Medical 
Center, and New York City and Chicago Head Start centers. CPP's 
successful adoption into diverse communities underscores the importance 
of partnering with individuals, families, communities, and healthcare 
practitioners to ensure a program's effective translation into real 
world settings.

                PALLIATIVE CARE AND END OF LIFE RESEARCH

    As the lead NIH Institute for end-of-life research, NINR supports 
evidence-based palliative care research that assists individuals, 
families, and healthcare professionals in managing the symptoms of 
advanced illness and planning for end-of-life decisions. Individuals of 
all ages with advanced illness can face protracted courses of decline, 
requiring that difficult decisions be made to ensure appropriate 
intervention and to maximize quality of life. NINR supports a 
palliative care research cooperative to enhance the evidence base for 
palliative care by carrying out multi-site research studies and 
clinical trials to be used to inform health practice and policy.
    NINR grantees are also evaluating palliative care interventions for 
patients with heart failure. Others are testing the efficacy of an 
integrated model of palliative care early in the cancer diagnosis 
process. The Institute also supports research on family members' 
perceptions and the importance of end-of-life strategies. These 
activities will provide for both optimal care and treatment for 
patients facing life-limiting conditions, and assist patients and 
family members.

                 RESEARCH TO IMPROVE CLINICAL PRACTICE

    As the healthcare providers most frequently interacting with 
patients, nurses are uniquely positioned to develop successful 
interventions to address treatment challenges. As our Nation's aging 
population continues to grow, the demand for critical care services is 
projected to increase. As a result, the number of patients transferred 
to long-term acute care hospitals, and the resulting costs, are 
expected to increase significantly. A recent NINR-funded study compared 
two methods for weaning patients from prolonged mechanical ventilation. 
Researchers found that one method, using a device known as a 
tracheostomy collar, resulted in earlier, successful weaning from 
mechanical ventilation. Implementing standard, best practice guidelines 
based on these findings could lead to shorter length of stays, better 
patient outcomes, and decreased healthcare costs. NINR will continue to 
facilitate the implementation of evidence-based treatment interventions 
into the clinical setting.

             INNOVATIVE TECHNOLOGIES TO ENHANCE HEALTHCARE

    Innovative technologies are gaining a larger role in healthcare, 
and nursing science can provide the foundation for developing novel 
advances that deliver personalized care and real-time information to 
individuals, families, and communities. For example, subtle changes in 
an individual's health status often indicate the early development of 
acute illness or worsening of chronic conditions, but detecting these 
changes can be difficult. NINR supported the development of an 
unobtrusive, inexpensive proactive disease management system that uses 
infrared sensors to monitor older adults' daily activities and 
automatically alert healthcare providers to changes in the patient's 
health status. This technology identified health conditions 1-2 weeks 
earlier than traditional assessment methods and led to improved 
functional abilities. Based on these successful results, the 
researchers hope to expand its use to other care facilities.
    For example, NINR supports scientists who are using information 
technology (IT) to assist patients in understanding the medications 
they are supposed to take and track whether they are actually taking 
the medications as prescribed. These scientists are developing an 
Electronic Medical Record (EMR)-based tool (the Medtable), which is now 
being evaluated for its effectiveness in provider/patient communication 
and whether it improves medication knowledge, adherence, and health 
outcomes among chronically ill adults with complex medication regimens.

              LOOKING TOWARD THE FUTURE: NURSE SCIENTISTS

    This Nation is facing complex healthcare challenges, and nurses and 
nurse scientists will play a pivotal role in addressing these issues. 
Since its inception, the training and career development of an 
innovative and diverse scientific workforce have been fundamental to 
NINR's mission. NINR supports nurse scientists and promotes earlier 
entry of nurses into research by providing research fellowships and 
career development awards. A recent initiative, the Scholars Training 
for the Advancement of Research (STAR) program, provides additional 
resources for institutions to support the ``fast-track'' training of 
outstanding undergraduate nursing students who are interested in 
pursuing a Ph.D. NINR training programs produce future nursing school 
faculty to strengthen the nursing workforce.
    In closing, NINR appreciates the opportunity to support science 
that can significantly improve the health of the Nation. The Institute 
provides innovative nursing science that becomes the evidence-based 
practice for clinical care. NINR will continue its mission to improve 
the quality of life by advancing nursing science to shape the future 
direction of healthcare.
                                 ______
                                 
 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 2014 President's budget request for the National Human 
Genome Research Institute (NHGRI). The fiscal year 2014 budget of 
$517,319,000 includes an increase of $5,061,000 above the comparable 
fiscal year 2012 level of $512,258,000.

       THE LAST DECADE OF GENOMICS HAS CHANGED BIOMEDICAL SCIENCE

    This year, we celebrate the tenth anniversary of the completion of 
the Human Genome Project (HGP). An ambitious scientific endeavor 
likened to biology's ``moon shot,'' HGP catalyzed profound changes for 
many areas of biomedical research and beyond. To provide a perspective 
about these changes, it is illustrative to compare the ``state-of-the-
art'' at the beginning of HGP in 1990, at its completion in 2003, and 
now. To place these three-time points in a cultural context, in 1990 
Americans communicated by phone and fax; in 2003 it was email; and in 
2013 it is the tweet.
    Just as technology development has transformed routine 
communications (from the phone call to the tweet), it has been the 
cornerstone of the Federal investment in genomics. During the HGP, it 
took 6-8 years of active sequencing and approximately $1 billion to 
generate that first sequence of the human genome. In 2003, that same 
feat would have required 3-4 months and $10-50 million. Today, a human 
genome can be sequenced in approximately 1-2 days for a mere $3-5 
thousand. As the time and cost have plummeted, the power of genomic 
strategies to advance research and the volume of generated genomic data 
have increased profoundly.
    Why is this massive increase in capacity for data generation 
important? This extraordinary increase in data generation allows us to 
understand genome structure and function and through this knowledge to 
learn how genomes contribute to health and disease. For example, in 
1990, we knew of approximately 50 genes that, when mutated, caused a 
human disease; in 2003 that number was almost 1,500; and today, it is 
nearly 3,000. Further, knowledge about the genomic basis for our 
responses to medications--an area of science called pharmacogenomics--
has also grown steadily. In 1990, only four Food and Drug 
Administration (FDA)-approved drugs required labels that pointed out 
the relevance of a patient's genetic makeup for that medication; by 
2003, this number had increased to 46; and today, it stands at 106. In 
fact, genomic contributions to medical research have been so 
substantial that fully half of the 2012 ``Top 10 Medical 
Breakthroughs'' identified by ``Time Magazine'' \1\ reflected genomics 
accomplishments, and these were in large part supported and/or 
facilitated by NHGRI's research programs.
    Although extraordinary progress has occurred over the past decade, 
much remains to be learned about the genome's role in biology and 
disease, and how to translate that knowledge to improve health 
outcomes. At the conclusion of HGP, we were but at the beginning of an 
exciting, but long journey to learn how to apply genomic information to 
improve health.

                     LEARNING FROM THE DATA DELUGE

    A major challenge for genomics research is the handling, analysis, 
and interpretation of the large volumes of genomic data now routinely 
generated. Solving this will require innovative infrastructure and 
novel methodologies. In fiscal year 2014, NHGRI will support pioneering 
bioinformatics research across its research portfolio, from the use of 
cloud computing for efforts such as the 1000 Genomes Project to the 
development of novel clinical bioinformatics tools by the Clinical 
Sequencing Exploratory Research (CSER) program and the Electronic 
Medical Records and Genomics (eMERGE) Network, two flagship programs 
intended to study how to utilize an individual's genomic information in 
different clinical settings. Additionally, the Institute will provide 
key leadership within NIH for the Big Data to Knowledge (BD2K) 
initiative.
    Consistent with NHGRI's 2011 strategic plan, the Institute's 
portfolio spans a continuum from basic research to study genomic 
structure and function, to translational research to discover the 
genomic basis for disease, through efforts to use genomics to increase 
the effectiveness of healthcare. The ENCyclopedia of DNA Elements 
(ENCODE) project, a key effort to identify the `functional parts' 
within the human genome, published a landmark series of papers in 2012 
reporting a catalog of functional elements within the human genome. The 
ENCODE catalog is like a GPS map for the human genome--just as by 
zooming in on a GPS map of the United States (to find the location of 
points of interests like banks and gas stations), the ENCODE catalog is 
now routinely used by researchers worldwide to zoom in on regions of 
interest in the human genome that are important for their studies. In 
fiscal year 2014, NHGRI will begin to add another layer of knowledge to 
this map with the launch of the Genomics of Gene Regulation (GGR) 
initiative. GGR will fund research to decipher how genes are regulated 
and to understand how gene regulation affects the function of cells and 
tissues, human development, and disease.
    In fiscal year 2014, NHGRI also will continue advancing the 
discovery of the genomic bases of disease. For example, the search for 
genes that play a role in rare diseases will be accelerated through the 
work of NHGRI's Centers for Mendelian Genomics, as well as an 
extramural expansion of the highly successful NIH Undiagnosed Diseases 
Program. Through research programs such as the Large-Scale Genome 
Sequencing and Analysis Centers, the genomic underpinnings of common 
complex diseases, such as cancer, diabetes, autism, and Alzheimer's 
disease, will remain a focus within NHGRI's portfolio as well.

                     IMPLEMENTING GENOMIC MEDICINE

    With the increasing accessibility of genomic technologies, the 
utility of genomics is already being demonstrated in clinical areas 
such as pharmacogenomics, non-invasive prenatal testing, infectious 
disease diagnostics, and cancer. The largest class of drugs now with 
FDA-required pharmacogenomic information to guide use on their labels 
includes those used for the treatment of cancer. Further, genome 
sequencing to identify mutations in a tumor's DNA sequence is now 
commonplace in the research setting and beginning to be seen in the 
clinical setting. Current examples of genomics informing care include 
the widespread use of ``BRCA'' testing in patients with familial risk 
factors for breast and ovarian cancer, the use of testing to predict 
breast cancer recurrence, and the use of genomic diagnostic tests to 
determine the suitability of particular treatments such as trastuzumab 
(Herceptin) use in breast cancer, vemurafenib (Zelboraf) use in 
melanoma, or crizotinib (Xalkori) use in lung cancer.
    In fiscal year 2014, NHGRI also will continue extending its 
portfolio to investigate the methods and evidence needed to integrate 
genomics as a standard component of clinical care. Both existing (e.g., 
CSER program) and new (e.g., Genomic Medicine Pilot Demonstration 
projects and the Genomic Sequencing and Newborn Screening Disorders 
program) initiatives will be carried out by integrated research teams 
that include clinicians, scientists, and bioethicists. These multi-
disciplinary groups will examine the medical as well as the ethical, 
social, and legal issues involved with making genomic data an 
essential, broadly accessible and broadly desirable element to inform 
clinical care. In fiscal year 2014, the Institute will continue 
supporting research pertaining to the pursuit of genomic research and 
the realization of genomic medicine, including protecting research 
participant privacy, determining when to return individual results, and 
how to handle unanticipated, but clinically important, ``incidental 
findings''.
    Through these and other programs, NHGRI will continue to lead the 
field of genomics in an effort to benefit the broad biomedical research 
enterprise and to realize the goal of advancing human health through 
genomics research.
---------------------------------------------------------------------------
    \1\ http://healthland.time.com/2012/12/04/top-10-health-lists/
slide/junk-no-more/.
---------------------------------------------------------------------------
                                 ______
                                 
  Prepared Statement of Roderic I. Pettigrew, M.D., Ph.D., Director, 
      National Institute of Biomedical Imaging and Bioengineering

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute of Biomedical 
Imaging and Bioengineering (NIBIB) of the National Institutes of Health 
(NIH). The fiscal year 2014 NIBIB budget request of $338,892,000 is 
$1,164,000 more than the comparable fiscal year 2012 level of 
$337,728,000. The mission of NIBIB is to improve human health by 
leading the development and accelerating the application of biomedical 
technologies. The Institute is committed to integrating the engineering 
and physical sciences with the life sciences to advance basic research 
and medical care. As we enter our second decade as an NIH Institute, 
NIBIB is continuing to build on that integration.
    From wound healing to finding ways for the human body to create new 
cartilage for damaged joints, advances in regenerative medicine are 
helping wounded warriors and an aging population. Robotic leg 
prostheses with powered knee and ankle joints and other efforts in 
rehabilitation engineering hold the promise of giving once unimaginable 
independence to people who are severely paralyzed or have lost limbs. 
Advances in the field of nanotechnology, such as the ability to deliver 
drugs directly into tumors while sparing healthy tissue, and using 
imaging technologies for non-invasive treatment as well as diagnostics, 
hold the potential to make healthcare more precise and more effective 
for patients.

                   ADVANCES IN REGENERATIVE MEDICINE

    NIBIB is at the forefront of the developing field of tissue 
engineering and regenerative medicine, and already advances in stem 
cell research are being developed to aid our wounded warriors and the 
general population. Working toward this goal is the Armed Forces 
Institute for Regenerative Medicine (AFIRM), which includes NIBIB-
funded researchers and more than thirty U.S. universities and 
companies. Research supported by AFIRM has developed advanced treatment 
options and accelerated delivery of regenerative medicine therapies to 
treat the most severely injured U.S. service members. An exciting 
example of just one of the many innovative projects under way is the 
development of bioprinting of skin for battlefield injuries. This 
technology uses a bioprinter that creates and delivers skin cells and 
biomaterials to rapidly cover large wounds, which are a major cause of 
morbidity and mortality in severe burn injuries in civilians and 
military personnel. Other efforts are focusing on the difficult repair 
of segments of bone and nerve that are lost or damaged following 
traumatic injuries.
    In the general population, injury to cartilage can lead to joint 
pain and arthritis. One regenerative medicine project may help patients 
with knee injuries to successfully regenerate new, working cartilage 
through an innovative technique developed by NIBIB-funded researchers. 
The technique uses an engineered `biogel' scaffold (a structure that 
supports and holds cells together) that solidifies when exposed to 
light, combined with a strong biological adhesive that covers the 
injured area and provides an environment that promotes the growth of 
cartilage-producing cells. This successful research led to a small 
clinical trial in patients undergoing microfracture surgery, a first-
line therapy for cartilage repair where holes are drilled in the 
cartilage to encourage new growth. Patients who received the biogel and 
adhesive, in addition to microfracture surgery, had improved cartilage 
growth, less scarring, and decreased pain at 6 months post-surgery, 
when compared to microfracture without the biogel treatment. The 
technique has the potential to transform the field of knee cartilage 
repair, which affects many people and is difficult to treat 
successfully. A larger clinical trial using this promising technique is 
currently in progress. While the clinical trials are not funded by 
NIBIB, these are examples of public private partnerships of translating 
research to clinical settings.

           REHABILITATION ENGINEERING TO ENABLE INDEPENDENCE

    Overcoming major barriers, researchers have now developed an 
implantable, compact, self-contained device for the sensing and 
transmission of brain activity. The device is an important step toward 
the development and use of brain-computer interfaces that harness the 
power of thought to remotely control computers, prosthetics, and other 
devices. The new wireless device allows the user more freedom of 
movement than the earlier version, which was connected to a computer 
with wires and cables and greatly limited the range of movement. The 
small device is fully implanted beneath the skin much like a cochlear 
implant. It is capable of recording neural activity from 100 different 
sites and converting this neural activity into digital signals. It also 
transmits these digital signals to a wireless receiver located some 
distance outside the body. The device is recharged wirelessly. Initial 
tests in animals were successful at recording data in real-time for 
more than a year. The device may one day be used to control prosthetic 
arms and other devices, motorized wheelchairs, or for diagnostic 
monitoring in disorders such as in epilepsy, where patients currently 
are tethered to the bedside during assessment.

                 ENGINEERING ADVANCED MEDICAL SOLUTIONS

    NIBIB continues to support technologies for more efficient and 
effective drug delivery. Key developments include the creation of 
nanoparticles that can target powerful cancer-killing medications to a 
tumor without inadvertently damaging surrounding healthy tissues. In 
addition to successfully targeting the tumor, a drug that is tethered 
to a nanoparticle can only reach its target if it survives in the 
blood, where the immune system is constantly removing foreign 
particles. To address this technical hurdle, researchers devised a 
stealth coating for nanoparticles that tricks the immune system into 
ignoring the particles. By disguising the nanoparticles to chemically 
look like ``self'', the immune system does not clear the particles, and 
more medication can be delivered to their target tumors. Using this 
method, tumors in mice were reduced by 70 percent compared with tumors 
that were targeted with the cancer drug but without the nanoparticle 
and stealth coating. Based on these encouraging results, human clinical 
trials using stealth-coated nanoparticles to deliver anticancer drugs 
are currently under way. This technology might one day be used to 
deliver genes for gene-therapy treatment or to enhance biocompatibility 
and durability of larger foreign objects such as pacemakers and 
implants, whose function can degrade over time due to attacks by the 
immune system.
    NIBIB also supports research that harnesses the power of magnetic 
resonance imaging (MRI) and the faster metabolic rates of cancer cells 
than normal cells to develop a biomarker for prostate cancer. The goal 
is to use the biomarker to distinguish which prostate cancer disease is 
aggressive from those that are indolent where watchful waiting may be 
the appropriate course of action. Researchers have developed a 
technique using hyperpolarized carbon-13 (C-13) compounds to measure 
the faster metabolism of glucose in prostate cancer. In this method, by 
``hyperpolarizing'' the carbon isotope, investigators are able to 
increase the target signal by about 10,000-fold, making this carbon 
labeled signal much more readily detectable. The researchers developed 
a system for synthesizing, hyperpolarizing, and rapidly delivering 
carbon-13-labeled pyruvate, a product of glucose metabolism. The 
metabolic changes of pyruvate to lactate serve as a biomarker or 
indication for prostate cancer as the disease progresses and provide 
useful measures of the aggressiveness of the tumor. Preliminary 
clinical results show promise for this approach for cancer biomarkers.

           NEW USES OF ULTRASOUND FOR DIAGNOSIS AND TREATMENT

    The immune system's natural killer (NK) cells are those that find 
and destroy foreign substances in the body. A human NK cell line, NK-92 
can be used to target and destroy tumors. However, this promising 
strategy to use the immune system to fight tumors is not possible for 
use in the brain because NK cells cannot penetrate the blood brain 
barrier (BBB). NIBIB-funded researchers developed an experimental 
system using ultrasound to deliver NK-92 cells to tumors in the brain. 
The movement of the NK cells into the tumor was monitored with and 
without focused ultrasound disruption of the BBB. Using MRI, 
researchers found that approximately 1 NK cell for every 100 tumor 
cells had reached the brain when using focused ultrasound to open the 
BBB, compared to 1 NK cell per 1,000 tumor cells when ultrasound was 
not used. These preclinical results suggest that the tumor-killing 
ability of immune natural killer cells combined with focused ultrasound 
has tremendous potential for targeting and destroying brain tumors.
    Another new ultrasound imaging technique developed by NIBIB-
supported researchers can noninvasively detect tumors and fibrosis in 
the liver. Typically, liver disease is diagnosed using liver biopsy, a 
surgical procedure that can be painful and cause complications. This 
new ultrasound-based technique, called Acoustic Radiation Force Impulse 
imaging does not produce harmful ionizing radiation and is relatively 
inexpensive compared with other imaging modalities. This means it can 
be used more frequently to track the progression of fibrosis. In 
contrast to a biopsy, which can only examine a small discrete sample of 
the liver, this method examines the entire liver. The technique uses 
focused, high intensity sound waves to produce ``push-pulses'' that 
generate shear within tissue. Ultrasound is then also used to monitor 
the tissue response. The tissue response is related to the stiffness 
properties and structure of the liver, and is displayed as a high 
resolution, qualitative image. This technique can also produce 
quantitative stiffness measurements based on the speed of the shear 
waves. These measurements are used to quantify specific levels of 
fibrosis that can be used to classify different stages of liver 
fibrosis or tumors.
    Yet another advance is the use of the mechanical force of 
ultrasound to breakup thrombi and minimize the damage to heart muscle 
during a heart attack. Researchers first demonstrated in porcine models 
of coronary arteries blocked by blood clots or thrombosis, that 
conventional ultrasound using a high ``mechanical index'' in 
conjunction with micro-bubbles and a conventional clot dissolving agent 
achieved greater restoration of flow in the blocked artery. 
Consequently, there was also greater heart muscle salvaged. In an 
initial human study, this technique was successfully and safely used in 
patients who presented at a hospital with evidence that a heart attack 
had begun. If the promise of these preliminary studies continues, this 
could be implemented at hospitals throughout the country as a first-
line treatment to minimize damage in evolving heart attacks.
    NIBIB will continue to target the unique scientific opportunities 
of the 21st century in rehabilitation engineering, regenerative 
medicine, and advanced imaging techniques to improve disease diagnosis 
and treatment. This era promises a revolution in employing technology 
to realize innovations that address healthcare challenges, reduce 
disease mortality and morbidity, and enhance quality of life and 
improve the health of the Nation.
                                 ______
                                 
 Prepared Statement of Christopher P. Austin, M.D., Director, National 
              Center for Advancing Translational Sciences

    Mr. Chairman and members of the committee: It is a privilege to 
present to you the President's budget request for the newly established 
National Center for Advancing Translational Sciences (NCATS) for fiscal 
year 2014. The fiscal year 2014 budget for NCATS is $665,688,000, which 
represents an increase of $91,391,000 over the fiscal year 2012 
comparable level of $574,297,000. The request includes $50 million for 
the Cures Acceleration Network (CAN), an increase of $40 million over 
fiscal year 2012. CAN will fund initiatives designed to address 
scientific and technical challenges that impede translational research, 
including support for the Tissue Chips for Drug Screening Initiative, 
the Discovering New Therapeutic Uses for Existing Molecules Program, 
and other programs. Common Fund support of these programs will end by 
fiscal year 2014, at which time they will be funded through the NCATS 
direct appropriation.
    NCATS' mission is to catalyze innovations that enhance the 
development, testing, and implementation of diagnostics and 
therapeutics across a wide range of human diseases and conditions. In 
the short time since its founding in December 2011, NCATS has become a 
hub of innovation for translational sciences at NIH and in the broader 
translational ecosystem that includes the pharmaceutical, 
biotechnology, venture capital, regulatory, and patient advocacy 
communities. The Center has launched several major research 
initiatives, cultivated promising strategic partnerships, and 
established a presence at NIH and in the community. For example, NCATS' 
Therapeutics for Rare and Neglected Diseases (TRND) program was 
responsible for the development and first-in-human testing of new 
therapies for four different diseases in a period of 16 months via 
novel partnership structures. Another achievement was the agreement 
with the Defense Advanced Research Project Agency and the Food and Drug 
Administration (FDA) to initiate an innovative grant program to create 
new tools for predicting drug toxicity. The goal is to fund researchers 
who will create 3-D ``chips,'' which are miniature models with the 
structure and function of human organs. These chips will be used to 
test drugs to see if they are safe or toxic to humans, thus saving 
researchers time and money compared to current methods. NCATS also 
developed the New Therapeutics Uses for Existing Molecules initiative, 
a breakthrough partnership program with eight pharmaceutical companies 
to find new uses for existing drugs owned by these companies. The eight 
companies agreed to make many of their molecular compounds available to 
outside researchers for testing for new therapies. These compounds have 
already undergone safety and toxicity testing in humans and so provide 
researchers with valuable data that may help speed the research process 
forward. In addition, NCATS has created template agreements with the 
drug companies ready for use by the investigator, thus saving the time 
the investigator would have spent negotiating an agreement with the 
drug company.
    Collaborations among Government, academia, industry and nonprofit 
patient organizations are crucial for successful translation. For 
example, support from the NCATS' Clinical and Translational Science 
Award (CTSA) program at the University of Pittsburgh contributed to the 
development of a robotic arm that allowed a quadriplegic patient to 
feed herself using just her thoughts. This remarkable achievement was 
the result of NIH, the Department of Defense, the Department of 
Veterans Affairs (VA), the FDA, a private foundation, two academic 
research centers, and a private company working together, which made 
this possible.

            AVOIDING DUPLICATION, REDUNDANCY AND COMPETITION

    A fundamental principle of NCATS is that it addresses the many 
translational problems that are not undertaken by industry because this 
early-stage research hasn't yet proven to be commercially viable. Thus, 
NCATS is explicitly complementary to efforts in industry. Our work is 
in the ``precompetitive'' space where industry and NIH/academia have 
long collaborated to mutual benefit.
    In addition to this general positioning of NCATS as an ``adaptor'' 
or ``intermediary'' between academic and industry science, many 
specific initiatives have been put in place to prevent duplication, 
redundancy, and competition with industry. We recently published a 
Notice in the Federal Register that enumerates and seeks comments on 
the procedures and methods NCATS is using to ensure that industry is 
both aware of and able to provide input on our activities and planned 
initiatives. Some of these methods include frequent updates to the 
NCATS Web site, an NCATS Director's newsletter, publication of Requests 
for Information on proposed programs, open public meetings to which 
industry representatives are specifically invited, and meetings 
arranged with industry trade groups and associations.

 PRE-CLINICAL RESEARCH: CONNECTING LABORATORY POTENTIAL WITH CLINICAL 
                                PROMISE

    NCATS is active in the development, demonstration, and 
dissemination of a broad range of technologies, tools, and resources 
that facilitate collaborative pre-clinical testing and first-in-human 
clinical trial implementation. For example, NCATS' Matrix Screening 
``Platform,'' or testing process that includes specific equipment, is a 
transformative technology that identifies combinations of drugs to 
treat diseases resistant to single drugs, which is particularly 
important for treatment-resistant cancers. Since this testing is done 
in a high-speed fully automated robotic format, thousands of drug 
combinations can be tested in a single day to determine which are best 
able to kill the cancer cells while minimizing toxic side effects.
    Determining toxicity is a major roadblock in the advancement of 
promising discoveries. The Tox21 Program, along with the Environmental 
Protection Agency, the National Institute for Environmental Health 
Sciences, and the FDA, is testing over 10,000 drugs and environmental 
chemicals for hundreds of activities relevant to toxicity, with all 
data being made publicly available.

            CLINICAL RESEARCH: DEMONSTRATING MEDICAL BENEFIT

    Clinical research is conducted to test the safety and effectiveness 
of a new or improved diagnostic or therapeutic intervention, more 
effectively diagnose a disease, demonstrate the utility of biomarkers 
or prognostic risk factors, and discover better ways to implement 
health-improving interventions. The centerpiece of this area at NCATS 
is the CTSA program.
    The purpose of the CTSA program (http://www.ncats.nih.gov/research/
cts/ctsa/ctsa.html) is to support the entire spectrum of translational 
research in order to accelerate the transition of laboratory 
discoveries into patient studies and into clinical practice. Through 
integrated homes that build on academic institutions' scientific 
strengths, CTSAs provide expertise, resources, and workforce training, 
which improve the quality, validity, generalizability, and efficiency 
of clinical and translational research. For example, a team of 
scientists with support from the University of California, Davis, CTSA 
developed a test to determine the prevalence of a debilitating disease, 
called Fragile X, in the general population. This information will help 
researchers create screening and diagnostic strategies and allow 
planning of clinical trial recruitment strategies for new Fragile X 
therapies.

                         FOCUS ON RARE DISEASES

    Targeting support to accelerate new treatments for rare diseases is 
a major priority for NCATS. About 6,000 rare diseases affect an 
estimated 25 million Americans; and, according to the Office of Orphan 
Products Development, FDA, 450 orphan drugs have been approved, which 
together treat only 250 of the 6,000 diseases. Discoveries about the 
molecular basis of rare diseases based on the Human Genome Project 
offer unprecedented scientific opportunities to change systematically 
this landscape, by approaching rare diseases and their treatment as a 
holistic systems-based problem, and NCATS is capitalizing upon these 
opportunities. For example, the TRND program speeds the development of 
new treatments for rare diseases of very low prevalence and otherwise 
commercially neglected tropical diseases. It forms public-private 
partnerships, which leverage the unique strengths and capabilities of 
each party. Partnerships with disease foundations and/or biotech firms 
helped bring promising therapies to the first-in-human testing stage 
for chronic lymphocytic leukemia, sickle cell disease, hereditary 
inclusion body myopathy, and Niemann-Pick Type C disease.

                               CONCLUSION

    NCATS has sought to establish new technologies and paradigms that 
can be implemented broadly to improve the efficiency of the 
translational process for all and to broker collaborative development 
of new interventions. We are grateful for the support of this 
subcommittee for this new Center and look forward to sharing progress 
with you each year.
                                 ______
                                 
 Prepared Statement of Roger I. Glass, M.D., Ph.D., Director, Fogerty 
                          International Center

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the Fogarty International Center 
(FIC) of the National Institutes of Health (NIH). The fiscal year 2014 
FIC budget of $72,864,000 includes an increase of $3,371,000 over the 
comparable fiscal year 2012 appropriation of $69,493,000.
    From leading the call for an AIDS-free generation to developing 
vaccines and therapeutics for diseases that affect populations 
worldwide, the United States is a global leader in health research and 
scientific advances that improve the lives of Americans and people 
across the globe. These discoveries are often made by U.S. and foreign 
scientists working in close collaborations that enable the best and 
brightest minds to tackle complex health challenges together. The 
Fogarty International Center therefore supports innovative training and 
research programs for U.S. and low- and middle-income country (LMIC) 
scientists that strengthen the research capabilities and catalyze the 
international scientific partnerships that lead to research discovery 
and improved health. By investing in current and future leaders in 
global health research and strengthening the long-term capacity of 
research institutions to provide robust and sustainable platforms for 
cutting-edge science, Fogarty advances the goals and extends the 
leadership of the NIH and the U.S. Government in science and research, 
while playing a vital role in building the capacity needed to 
successfully tackle critical health challenges.

   RECRUITING AND RETAINING DIVERSE SCIENTIFIC TALENT AND CREATIVITY

    Fogarty programs have supported long-term research training for 
more than 4,500 scientists worldwide, in collaboration with more than 
230 U.S. and LMIC research institutions. These investments provide 
unique training opportunities for early-career global health 
researchers, and aid in the retention of diverse scientific talent in 
the research enterprise. The vast contribution of FIC programs can be 
seen in the over 5,000 PubMed publications citing FIC awards over the 
last 5 years alone. Today's complex public health challenges benefit 
when investigators from diverse fields work together to produce 
transformative advances in science and technology. Fogarty's unique 
``Framework Program for Global Health Innovation'' trains multi-
disciplinary teams of postdoctoral researchers to work together to 
produce fresh insights into global health problems and develop 
effective innovations for implementation in low-resource settings. For 
example, with Fogarty support, a team of medical, engineering, and 
architecture researchers from Boston, South Africa, and Peru is 
designing and validating effective, affordable prototypes for air 
disinfection. This work can not only help prevent airborne infections 
such as tuberculosis and influenza from spreading in the low-resource 
settings where they cause significant illness and death, but can also 
potentially help higher income countries such as the United States 
improve their programmatic approaches to airborne infection.
  --Funded under the U.S. President's Emergency Plan for AIDS Relief 
        (PEPFAR) in collaboration with 18 NIH Institutes and Centers, 
        Fogarty and the Health Resources and Services Administration 
        (HRSA) jointly co-administer an innovative cross-U.S. 
        Government initiative funded primarily by the Office of the 
        Global AIDS Coordinator (OGAC) that is transforming medical 
        education and research training for medical students in 12 
        African countries. The 13 direct MEPI awardees and more than 40 
        partner institutions use a broad range of state-of-the-art 
        teaching and collaboration tools to train the next generation 
        of scientific leaders to solve their country's most pressing 
        health problems--from HIV/AIDS to maternal and child health, 
        and non-communicable conditions such as mental health and 
        cardiovascular disease. MEPI is increasing the quality, 
        quantity, and retention of medical faculty and physicians with 
        research skills, and building relationships with the public 
        sector partners that promote sustainable research capacity. For 
        example, Zimbabwe's Ministry of Education is now co-funding the 
        University of Zimbabwe's MEPI work.

                         TRANSLATIONAL SCIENCE

    Fogarty programs support researchers who are generating the 
critical scientific evidence that can be applied to specific 
interventions, policies, and programs, and make a difference in 
fighting disease and improving health.
  --In recent years, we have seen that infectious diseases from animal 
        as well as human hosts can cause outbreaks that pose 
        significant health and economic threats to the U.S. and other 
        countries, Fogarty's ``Research and Policy in Infectious 
        Disease Dynamics (RAPIDD)'' program--co-funded by the 
        Department of Homeland Security (DHS)--brings together senior 
        infectious disease modelers and postdoctoral fellows to conduct 
        the research and develop infectious disease modeling approaches 
        that can help the U.S. and other policymakers plan for and 
        respond to potential infectious disease threats. ``RAPIDD'' 
        models have contributed to a greater understanding of how Avian 
        Influenza and Hand, Foot, and Mouth disease can develop into 
        outbreaks from an initial case, and how these outbreaks can be 
        controlled effectively.

           TODAY'S BASIC SCIENCE FOR TOMORROW'S BREAKTHROUGHS

    Fogarty supports catalytic basic biomedical and behavioral research 
that can lead to tomorrow's breakthroughs.
  --Despite recognition of a looming antibiotic resistance crisis in 
        the U.S. and around the world, the number of new antibiotics 
        reaching the clinic continues to decline sharply, and most 
        recent discovery has been confined to minor modifications of 
        known antibiotics, with limited new therapeutic potential. The 
        Fogarty International Cooperative Biodiversity Groups (ICBG) 
        program, is working to change this. Fogarty-funded researchers 
        have developed an innovative and cost-effective approach to 
        antibiotic discovery, using an ``antibiotic mode of action 
        profile'' (BioMAP). BioMAP is a ground-breaking tool that can 
        be used to facilitate new natural products antibiotic discovery 
        and address the looming antibiotic crisis in the United States 
        and around the world.
  --Brain disorders such as epilepsy and Alzheimer's pose significant 
        health problems around the globe. Fogarty's ``Brain Disorders'' 
        program supports cutting-edge basic science research in LMICs 
        on the nervous system--research that could lead to new 
        diagnostics, prevention, and treatment strategies. In India, 
        for example, Fogarty grantees are exploring why Alzheimer's 
        affects Indian populations less than populations in developed 
        countries, with the goal of discovering useful evidence to 
        understand and mitigate Alzheimer's globally. In Uganda, 
        Fogarty-supported research is creating a base of knowledge on 
        dementia in those with long-term HIV infection, obtaining data 
        on prevalence, risk factors, and possible differentiation by 
        HIV sub-type that will be useful in understanding the course of 
        the disease and developing potential interventions worldwide.

                           FUTURE CHALLENGES

    The need for sustainability poses a significant challenge for 
investments in global health research and research training. Fogarty 
investments continue to evolve with increasing research capabilities in 
LMICs in order to build on successes and support the training of 
individual scientists and strengthen research institutions. Fogarty's 
deep regional expertise will continue to serve as a unique resource for 
NIH and individual foreign scientists, institutions and countries that 
are seeking new models and mechanisms that enable collaboration around 
areas of mutual interest. In addition, Fogarty will increase support 
for institutional networks and hubs for data collection and sharing. 
When such sharing platforms are built around a core of trained 
individuals and strengthened institutions, they can harness effectively 
the different strengths of these institutions, and promote enhanced 
efficiencies and more robust, collaborative science.
  --Fogarty envisions that its U.S.-LMIC ``GEOHealth'' hubs will become 
        global leaders in the collection, management, synthesis, and 
        interpretation of data on environmental and occupational 
        health, serving the larger multi-national regions in which they 
        reside as well as supporting research of great relevance to 
        both these LMIC regions and the U.S.
  --In sub-Saharan Africa, universities supported by ``MEPI'' are 
        emerging as regional training centers and upgrading the 
        technology to enable distance learning and resource-sharing 
        among institutions. This model is revolutionizing African 
        medical education and research training by enabling partner 
        institutions across Africa to pool their areas of expertise, 
        share teaching tools, and ensure that all students receive the 
        highest-quality instruction from the continent's best qualified 
        faculty and researchers.
    In an increasingly interconnected world, the U.S. is often called 
upon to play a leading role in addressing the world's most pressing 
challenges. Fogarty programs harness the capabilities of the U.S. as a 
leader of biomedical research, extend the frontiers of science, 
accelerate discovery, improve the health of Americans and people across 
the globe, and help the U.S. continue to compete and lead in science.
                                 ______
                                 
 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 budget request for the National Library of Medicine 
(NLM) of the National Institutes of Health (NIH). The fiscal year 2014 
budget of $382,252,000 includes an increase of $17,365,000 over the 
comparable fiscal year 2012 level of $364,887,000. Funds have been 
included to allow the National Center for Biotechnology Information 
(NCBI) to meet the challenges of collecting, organizing, analyzing, and 
disseminating the deluge of data emanating from research in molecular 
biology and genomics.
    As the world's largest biomedical library and the producer of 
internationally trusted electronic information services, NLM delivers 
trillions of bytes of scientific data and health information to 
millions of users every day. Many searches that begin in Google or a 
mobile ``app'' actually retrieve information from an NLM Web site. NLM 
is a key link in the chain that makes biomedical research results--DNA 
sequences, clinical trials data, toxicology and environmental health 
data, published articles, and consumer health information--readily 
available to scientists, health professionals, and the public. A leader 
in biomedical informatics and information technology, NLM also conducts 
and supports leading-edge research and development in electronic health 
records, clinical decision support, natural language processing, 
information retrieval, imaging, computational biology, 
telecommunications, and disaster response.
    NLM's programs and services directly support NIH's key initiatives 
in basic research, translational science, and research training, as 
well as in Big Data. The Library organizes and provides access to the 
published medical literature and 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. NLM's 
PubMed Central (PMC) provides essential infrastructure for the NIH 
Public Access Policy, which since 2008 has made published NIH-funded 
research freely and permanently available to the public.
    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' Web sites, as well as 
connecting to vast collections of scientific data. NLM is a primary 
source for results of patient-centered outcomes research, providing 
access to evidence on best practices to improve patient safety and 
healthcare quality. The Library maintains an expanding collection of 
full-text guidelines, evidence summaries, and systematic reviews from 
authoritative agencies and organizations around the world.
    NLM is also a hub for the international exchange and use of data 
utilized in molecular biology, genomics, and clinical and translational 
research. Many NCBI databases, including dbGaP, the Genetic Testing 
Registry (GTR) and ClinVar, are fundamental to the identification of 
important associations between genes and disease, and to the 
translation of new knowledge into better diagnoses and treatments. 
NLM's Lister Hill National Center for Biomedical Communications 
operates ClinicalTrials.gov, the world's most comprehensive clinical 
trials database. It contains registration data for more than 145,000 
clinical studies with sites in 185 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 
(FDA) Amendments Act of 2007. Summary results are available for nearly 
9,000 completed trials of FDA-approved drugs, biological products, and 
devices--providing a new and growing source of evidence on efficacy and 
comparative effectiveness. NLM will leverage experience with these 
resources and its research in related fields to contribute to NIH 
efforts to improve access to other types of NIH-funded Big Data.

          HEALTH DATA STANDARDS AND ELECTRONIC HEALTH RECORDS

    Electronic health records (EHRs) with advanced decision-support 
capabilities and connections to relevant health information are 
essential to improving healthcare and helping Americans manage their 
own health. For 40 years, NLM has supported seminal research on 
electronic patient records, clinical decision support, and health 
information exchange, including concepts and methods now reflected in 
EHR products and personal health record tools. As the Department of 
Health and Human Services (HHS) coordinating body for clinical 
terminology standards, NLM works closely with the Office of the 
National Coordinator for Health Information Technology and the Centers 
for Medicare and Medicaid Services to facilitate adoption and 
``meaningful use'' of EHRs. NLM supports, develops, and distributes key 
terminology standards now required for U.S. health information 
exchange. To help EHR developers implement standard terminologies, NLM 
produces related software tools, frequently used subsets, and mappings 
to administrative code sets, and provides the authoritative versions of 
terminology value sets for required clinical quality measures. NLM's 
MedlinePlus Connect also supports meaningful use by providing a way for 
EHR products to link patients to high quality health information 
relevant to a specific health conditions, medications, and tests, 
directly from their EHRs.

                  INFORMATION SERVICES FOR THE PUBLIC

    This EHR connection builds upon NLM's extensive information 
services for patients, families and the public. The Library's 
MedlinePlus Web site provides integrated access to high quality 
consumer health information produced by all NIH components and 
Department of Health and Human Services (DHHS) agencies, other Federal 
departments, and authoritative private organizations. It 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 750,000 visits per day. 
Mobile MedlinePlus, also in both English and Spanish, reaches the large 
and rapidly growing mobile Internet audience.
    The ``NIH MedlinePlus'' magazine, in English and Spanish, is an 
outreach effort made possible with support from many parts of NIH and 
the Friends of the NLM. Distributed free to the public via physician 
offices, community health centers, libraries and other locations, the 
magazine reaches a readership of up to 5 million nationwide. Each issue 
focuses on the latest research results, clinical trials and guidelines 
from the 27 NIH Institutes and Centers.
    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 6,000-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.

            INFORMATION FOR DISASTER AND EMERGENCY RESPONSE

    NLM builds on proven emergency backup and response mechanisms 
within the NN/LM to promote effective use of libraries and information 
specialists in disaster preparedness and response. NLM conducts 
research on new methods for sharing and ensuring continued access to 
health information in emergencies, including as its contribution to the 
Bethesda Hospital Emergency Preparedness Partnership, a model of 
private-public hospital collaboration for coordinated disaster 
planning. NLM works with the Pan American Health Organization (PAHO) 
and the Latin American Network for Disaster and Health Information to 
promote capacity-building in disaster information management. In 
addition, NLM responds to specific disasters worldwide with specialized 
information resources appropriate to the need. Mobile apps and tools 
developed for first responders have been downloaded nearly 500,000 
times worldwide.
    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 E. Whitescarver, Ph.D., Director, Office of 
                             AIDS Research

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for fiscal year 2014 for the trans-NIH 
AIDS research program, which is $3,121,716,000. This amount is 
$46,921,000 above the comparable fiscal year 2012 level of 
$3,074,795,000. 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.

      NATIONAL INSTITUTES OF HEALTH AIDS RESEARCH ACCOMPLISHMENTS

    In the three decades since AIDS was first reported, NIH has been 
the global leader in research to understand, prevent, diagnose, and 
treat HIV and its many related conditions. From the development of the 
first blood test for HIV infection and the discovery and clinical 
testing of the first effective therapies, through today's research to 
determine whether a vaccine, microbicide, or eventual cure for AIDS 
will one day be possible, NIH research has transformed HIV from a 
mysterious and uniformly fatal infection into one that can be 
accurately diagnosed and effectively managed with appropriate 
treatment. A recent study estimated that 14.4 million life years have 
been gained since 1995 by the use of AIDS therapies developed as a 
result of NIH-funded research. Recent discoveries include:
  --Development of new treatments for many HIV-associated co-
        infections, comorbidities, malignancies, and clinical 
        manifestations;
  --Development of new strategies for the prevention of mother-to-child 
        transmission (MTCT), which have resulted in dramatic decreases 
        in perinatal HIV in the U.S., where now fewer than 100 babies a 
        year are born with HIV infection;
  --Demonstration of the first proof of concept that a vaccine can 
        prevent HIV infection and identification of potential immune 
        markers for protection;
  --Discovery of more than 20 potent human antibodies that can stop up 
        to 95 percent of known global HIV strains from infecting human 
        cells in the laboratory;
  --Demonstration of the first proof of concept that a microbicide gel 
        can prevent HIV transmission;
  --Demonstration that the use of antiretroviral therapy by infected 
        individuals can reduce HIV transmission to an uninfected 
        partner dramatically;
  --Demonstration of the feasibility of pre-exposure prophylaxis 
        (PrEP), the use of antiretroviral treatment regimens by 
        uninfected individuals to reduce their risk of HIV acquisition;
  --Discovery that genetic variants may play a role in enabling some 
        individuals, known as ``elite controllers,'' to control HIV 
        infection without therapy;
  --Critical basic science discoveries that continue to provide the 
        foundation for novel research; and
  --Advances in basic and treatment research aimed at eliminating viral 
        reservoirs in the body that for the first time are leading 
        scientists to design and conduct research aimed at a cure for 
        HIV/AIDS.

                           THE AIDS PANDEMIC

    In spite of these advances, the HIV/AIDS pandemic remains a global 
scourge. UNAIDS reports that in 2011, more than 34 million people were 
estimated to be living with HIV/AIDS; 2.5 million were newly infected; 
and 1.7 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 
25 million men, women, and children worldwide have already died. Around 
330,000 children were newly infected with HIV in 2011, a reduction of 
24 percent in just 2 years--from 2009-2011--a result of the 
distribution of HIV treatment to prevent mother-to-child transmission 
developed by NIH research.
    In the United States, the Centers for Disease Control and 
Prevention estimates that approximately 1.2 million people are HIV-
infected; approximately 50,300 new infections occur each year; and one 
in four people living with HIV infection in the U.S. is female. 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.

              COORDINATED TRANS-NIH AIDS RESEARCH PROGRAM

    The NIH AIDS research program is coordinated and managed by the 
Office of AIDS Research (OAR), which functions as an ``institute 
without walls'' with responsibility for AIDS-related research supported 
by nearly every NIH Institute and Center (IC). OAR coordinates the 
scientific, budgetary, and policy elements of the trans-NIH AIDS 
research.
    Through its unique trans-NIH planning, budget, and portfolio review 
processes, OAR identifies the highest priority areas of scientific 
opportunity and ensures that precious research dollars are invested 
effectively.
    In collaboration with both Government and non-Government experts, 
OAR develops the trans-NIH AIDS strategic Plan. The priorities of the 
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 ensures cross-
Institute collaboration. OAR has the authority to shift resources 
across ICs and areas of science to meet the needs of the changing 
epidemic and scientific opportunities.

               NEW SCIENTIFIC ADVANCES AND OPPORTUNITIES

    The advances made by NIH investigators have opened doors for new 
and exciting research opportunities to answer key scientific questions 
that remain in the search for strategies to prevent and treat HIV 
infection both in the U.S. and around the world. These advances 
represent the building blocks for the development of this trans-NIH 
AIDS research budget request. These include:
  --Basic research that will underpin further development of critically 
        needed ``vaccines and microbicides''.
  --Innovative multi-disciplinary research and international 
        collaborations to develop novel approaches and strategies to 
        eliminate viral reservoirs that could lead toward ``a cure for 
        HIV''.
  --Critical studies in the area of ``therapeutics as a method to 
        prevent infection'', including treatment to prevent HIV 
        transmission; Pre-Exposure Prophylaxis; a potential prevention 
        strategy, known as ``test and treat,'' to determine whether a 
        community-wide testing program with treatment can decrease the 
        overall rate of new HIV infections; and improved strategies to 
        prevent mother-to-child transmission. A key priority is to 
        evaluate prevention interventions that can be used in 
        combination in different populations, including adolescents and 
        older individuals.
  --Research to develop better, less toxic treatments and to 
        investigate how genetic determinants, sex, gender, race, age, 
        nutritional status, treatment during pregnancy, and other 
        factors interact to affect treatment success or failure and/or 
        disease progression.
  --Studies to address the increased incidence of malignancies; 
        cardiovascular, neurological and metabolic complications; and 
        premature aging associated with long-term HIV disease and 
        antiretroviral treatment (ART).
  --Research on the feasibility, effectiveness, and sustainability 
        required to scale-up interventions from a structured behavioral 
        or clinical study to a broader ``real world'' setting.

                           FUNDING PRIORITIES

    OAR has utilized its authorities to shift AIDS research resources 
across ICs to meet the new and exciting scientific opportunities in 
AIDS research. These shifts reflect the scientific priorities 
identified in the annual trans-NIH strategic planning and budget 
process and address the evolving clinical profile of the epidemic, 
changing demographics, and most recent scientific advances. In this 
budget request, OAR has provided increases to high-priority basic 
research (etiology and pathogenesis) that provides the underlying 
foundation for all HIV research. An important area will focus on 
research related to the potential for a cure or lifelong remission of 
HIV infection, including studies on viral persistence, latency, and 
reactivation. Increases are also provided for the development of 
vaccines and microbicides to prevent HIV infection. In order to provide 
those increases, OAR has reduced and redirected funds from natural 
history and epidemiology, therapeutic clinical trials, and training and 
infrastructure support.

                                SUMMARY

    The NIH 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 is 
not over, 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 to search for 
solutions to prevent, treat, and eventually cure AIDS.

    Senator Harkin. Thank you, again, Dr. Collins, for your 
statement, and for bringing us up-to-date.
    We'll begin a round of 5-minute questions.
    Who is running the time here? There we go.
    So we'll begin a round of 5-minute questions. I'm sure 
we'll have more than one round.

        FAVORING SAFER VERSUS INNOVATIVE RESEARCH PROJECT GRANTS

    So, Dr. Collins, as I said in my opening statement, I think 
you repeated it, that the reviewed NIH grants will drop to 
about 16 percent this fiscal year. I'm concerned that when 
money gets that tight, there's a tendency to shy away from 
awarding ideas that are thinking outside the box, and we've 
talked about that many times here with you over the last many 
years.
    I'm concerned that, consciously or unconsciously, your peer 
reviewers might tend to favor safer incremental advances and to 
avoid ideas that are bolder but may carry more risk. Any 
validity to that?
    Dr. Collins. Mr. Chairman, that's certainly an area of 
considerable concern for all of us, because imagine yourself on 
a study section where you have a big pile of exciting science 
in front of you and you know you're going to only be able to 
fund a very small number of those. You have in front of you a 
really powerful strong proposal that builds on previous work 
from an established investigator that you know is going to be 
successful, and then you got something over here that's a bit 
risky from an investigator who doesn't have the same track 
record.
    If it works, it could be groundbreaking, but you're not 
sure it's going to work. And in that setting where you would 
love to fund both, but you may not be able to, there can be a 
tendency then to go with what you know is going to produce 
results. But that could be just the wrong thing to do.
    We in NIH have a number of programs that aim to try to 
encourage innovation in this climate by setting up programs 
like the Pioneer Awards, the Transformative RO1s, the New 
Innovator awards. You can't apply to those programs unless you 
have an out-of-the-box idea.
    So, there's this common fund effort to do that, and many of 
the institutes have initiated efforts of that sort as well.
    But there's no question about it. There's no magic here in 
terms of loss of innovation potential. Just the fact that we're 
only funding 15, 16 percent or less of the applications that 
come in, there's a lot of innovation at the 18th percentile and 
the 22nd percentile. Most of us have a very hard time telling 
the difference between a grant that scores at the 11th 
percentile and the 17th. Yet, one is going to get funded and 
one may not.
    So, the real anxiety we all feel is how much talent is 
being wasted and how many ideas are not getting followed up on 
that could be.

          EFFECTS OF SEQUESTRATION ON RESEARCH PROJECT GRANTS

    Senator Harkin. So sequestration has an effect on that 
also?
    Dr. Collins. Absolutely, because sequestration drops the--
as we've all just mentioned, 700 grants that we hoped we would 
fund this year are not going to be. I'm sure in those 700 there 
were some great, innovative, out-of-the-box ideas.

                 NCI'S PROVOCATIVE QUESTION INITIATIVE

    Senator Harkin. Okay. I'm going to go to Dr. Varmus, 
talking about thinking out-of-the-box and everything. Tell us 
more about your Provocative Questions program, and what's the 
purpose, and how is it proceeding?
    Dr. Varmus. We did two things to try to ensure that we do 
the best we can, imperfect though that is, to address the 
concerns you and many others have raised about risk-taking 
under these adverse fiscal circumstances.
    The first thing we do is to look at a large number of our 
grant applications, and award grants even when the score is a 
little less than you might think is required for success by 
saying this is really innovative and addresses a very important 
issue.
    Number two, we set up some special programs, one of which 
is called Provocative Questions. These questions come from 
groups that we assemble around the country, interdisciplinary 
groups, people who haven't been in cancer research before, to 
raise some difficult questions that we think technology now may 
be prepared to address. We have these questions debated on our 
Web site. We then invite applications for answering about 24 
each year, and we're funding--last year, over 50; this year we 
hope more than that--to try to address the 24 questions that 
we've been selecting as particularly important and difficult 
questions.
    Too early to say how well we're going to do with this, but 
it's a way to try to guarantee some answer to the question 
you're appropriately raising.

                     BRAIN INITIATIVE: WHAT IS IT?

    Senator Harkin. I'll have a follow-up question on that 
later, but I wanted to ask Dr. Landis, in the short time I have 
left, about the new BRAIN Initiative.
    The President talked about mapping the brain, what does it 
mean? Someone compared it to, again, the Human Genome Project. 
But even at the beginning, some of us were there at the 
beginning, we knew what the end result was going to be, and we 
knew when it was going to end. We didn't know exactly when, but 
we knew what the end result was.
    What do we know about what is the end result? Is there 
something that we're looking to reach at a certain point in 
time?
    Dr. Landis. So, what we would really like to be able to do 
with the BRAIN Initiative is to understand how information is 
processed in circuits. As Dr. Collins told you, we're beginning 
to have better maps of connections between nerve cells in 
different regions of the brain. And, we can lay them out in 
circuits that control particular movements, vision, or hearing.
    But what we don't understand is how information is 
processed through those pathways. And in order to understand a 
number of psychiatric diseases and even neurodegenerative 
diseases, we have to understand how circuits work. We simply do 
not have the tools to do that now. So, that would be one of the 
major goals for the first 5 years of the BRAIN Initiative, to 
get better tools and technologies that will be able to help us 
track activity in circuits, and understand how information 
changes as it goes from one nerve cell in a circuit to another.
    Much more, as I've already said to Dr. Collins, much more 
complicated than just lining up the As and Cs and Ts and Gs, 
but could have as much, or even greater, impact. And he did 
agree with me on that.
    Senator Harkin. Yes, but 3 billion base pairs, we thought 
that was a lot. Now we're talking about a trillion or something 
like that. I don't know. We'll get back to that.
    Senator Moran.
    Senator Moran. Mr. Chairman, thank you very much.
    Dr. Collins, thank you very much for your compelling 
testimony.
    Dr. Varmus, thank you for coming to Kansas City and 
visiting a couple of facilities, a research facility and a 
hospital. But thank you especially for riding your bike to 
raise money for cancer research.
    Dr. Varmus. Along with the barbeque.
    Senator Moran. Along with the barbeque. That's right. That 
was the real inducement. Thank you very much for highlighting 
Kansas City barbeque.

                    BRAIN INITIATIVE: 10-YEAR BUDGET

    Dr. Collins, and this may be this is for Dr. Landis, 
because it's a follow-up to what the chairman was asking about. 
On the BRAIN Initiative, the budget documents are not very 
specific in regard to what we should expect as far as budget 
requests in the next 10 years.
    I was interested in what the goals are in the short term of 
this project. You outlined already what, at least in the first 
5 years, is the significant goal. But what would we as a 
committee, what would we as members of the Senate, expect the 
request to be in regard to the budget into the future?
    Dr. Collins. So, a very appropriate question. This is sort 
of like the genome project in 1988 where it was clear there was 
an opportunity, and it wouldn't happen without a coordinated 
effort, particularly the focus on technology. But nobody was 
quite sure at that point what the trajectory could look like as 
far as accomplishing that goal.
    We're in the process right now of trying to define that, 
Senator, in the long term, over the next 10 or 15 years. What 
could be accomplished? What would the steps be? What kind of 
technologies do we need? And what would the cost be?
    So, we brought together a really remarkable group of 
visionary neuroscientists in a group--co-chaired by Cori 
Bargmann from Rockefeller and Bill Newsome from Stanford along 
with 13 other remarkable folks--and we've asked them, in the 
course of the next few months, and they're hard at work at 
this, to lay out some initial milestones of what this project 
needs to accomplish. And by the summer of 2014, to have a much 
more detailed roadmap of where the BRAIN Initiative needs to go 
and how quickly it can get there.
    So, frankly, I don't have a clear answer to your question 
at the moment, in terms of what the budget trajectory of this 
might be over the next 10 or 15 years. We have to be sure we 
have the science plan laid out.
    Senator Moran. And there's no justifiable reason that we 
should expect that plan at this point? That's just not 
accomplishable, at this point? Before we start down this path, 
we're not going to know what to expect?
    Dr. Collins. I think at this point, it would be premature 
to try to attach budget numbers to a scientific plan that 
hasn't quite formed in a coalesced way and been embraced and 
endorsed by all of the scientific experts that we want to 
participate and to take part in this.
    So, it has always been our view that if you're going to try 
to start something really bold, the first step is to map out 
the science, and then you figure out, okay, what does that mean 
in terms of the timetables and the costs? Of course, you have 
to set priorities within the realistic envelope of what costs 
might be available to you.
    We recognize this may be a tough time to be starting a very 
ambitious project, but we just don't think it would be right to 
wait, given the opportunity.

     STATUS OF NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

    Senator Moran. Dr. Collins, this might be for you, as I 
don't think the National Center for Advancing Translational 
Sciences (NCATS) director is here.
    Dr. Collins. He is not.
    Senator Moran. Let me ask about the status of NCATS. I was 
supportive of its establishment. I think that is now about a 
year and a half ago. And I'd be interested in having you bring 
me up-to-date on its developments.
    One of the environments in which NCATS now works is that 
with the economic conditions we face, private drug companies 
can no longer make a financially sound business case to invest 
in new drug development projects. There's this gap, what has 
been described as a valley of death between scientific 
discovery on the one side and patient benefit and commercial 
success on the other.
    The goal of NCATS has been to fill that valley. What kind 
of success is NCATS having in doing that?
    Dr. Collins. Well, thank you for the question.
    Let me say right upfront how wonderful it's been for Chris 
Austin, the Director of NCATS, to work with folks in Kansas at 
the university and with the Leukemia and Lymphoma Society on a 
few groundbreaking projects. Particularly one on chronic 
lymphocytic leukemia (CLL), which is actually a good example of 
one of the things I want to mention that NCATS is catalyzed, 
and that is this whole idea of repurposing drugs that were 
developed for something but turned out to have a use for 
something else.
    The project they're working on with Kansas is a drug 
developed for rheumatoid arthritis, Auranofin, which turns out 
to have activity against leukemia, and more recently to the 
delight of all of us, also against a very resistant kind of 
cancer called mantle cell lymphoma.
    The CLL protocol is already well along in a clinical trial. 
This is an amazing quick turnaround, because if you had to 
start from scratch, it would take years and tens of millions of 
dollars to get to a clinical trial. But, if you can identify a 
compound and try it for a new purpose, you already have all 
that background data and you shave off years and many, many 
tens of millions of dollars in cost.
    So, NCATS is in fact catalyzing that kind of repurposing 
both for drugs that have already been approved but also in 
working with companies, eight of them, they have agreed to make 
58 compounds available for new uses that actually turned out 
not to be effective for the original use but the drugs are 
known to be safe.
    This is crowdsourcing, if you will, the opportunity to find 
a new use for a really heavily invested compound that may turn 
out to have failed for disease A but might be just the thing 
for disease B.
    NCATS is also working with the Food and Drug Administration 
(FDA) and with Defense Advanced Research Projects Agency 
(DARPA) on developing a new and very high-tech way of 
identifying whether or not a drug is going to be safe before 
you ever give it to that first human patient, using a biochip 
depending upon the stem cell, iPS cell technology.
    NCATS also serves now as the home for the largest 
investment in clinical and translational science, namely our 
Clinical and Translational Science Award (CTSA), of which they 
are 60 across the country in many of your States, and basically 
then bringing that network together in a way that makes the 
whole really much greater than the sum of the parts, sort of 
CTSA 2.0, as we are starting to call it.
    So, I think even though NCATS has only been around for, you 
know, a year and maybe 5 months, the evidence is very clear 
that this is an opportunity that we have grabbed on to. The 
private sector is enthusiastic about the way in which this 
serves as a complementary set of contributions to what they are 
doing. Academics are fired up about it. I think this has turned 
out to be a really good thing for NIH, too.
    Senator Moran. Very good.
    I assume you're the one who coined the phrase ``valley of 
death'' and now ``crowdsourcing.'' I will use it in my comments 
next.
    Dr. Collins. I don't think I can take credit, but you are 
welcome to use the terms.
    Senator Harkin. Senator Mikulski, Senator Shelby, Senator 
Cochran.
    Senator Mikulski.
    Chairwoman Mikulski. Thank you very much, Mr. Chairman.
    And, Dr. Collins, I want to welcome you and your entire 
team, and also other heads of institutes who are not at the 
blue table but are certainly always at the head of the line at 
the head table.
    I just wanted to just tell you in the warmest way, and to 
my colleagues, what a sense of joy and pride that I have 
representing NIH. The fact that it is located in my home State 
of Maryland, Senator Cardin and I both know that every day, to 
have such a premier institution is one of the reasons we want 
to be in the Senate, really to be an advocate for the kinds of 
resources, policy, and framework, so you get to be you and you 
get to be what the American people want you to do, which is to 
find cures to disease, to find containments of disease, to look 
for those things to even prevent them from happening or prevent 
them from escalating.
    So it's not only a source of pride, but I can tell you, as 
the chair of this full committee, I'm going to work with 
Senator Harkin and Senator Moran across party lines, to make 
sure they get the kind of allocation they need to do their job.
    Much has been said here about sequester. I'm not going to 
go into it in detail, but I'm concerned about the negative 
impact that it has, first of all on the people who work at NIH 
and those who participate in the extramural programs, like the 
University of Maryland, like Hopkins, like the great land-grant 
universities that, again, are out there working every day. 
That's the genius of what we do.
    It's not Government-owned and operated. It's also out there 
extramurally and also functioning around the world, because who 
you are, you talk to the others around the world.
    And, therefore, we need to look at the impact of sequester 
on jobs, on the economy, and not only on our reducing public 
debt today, but the impact on growth.
    I am just struck by what you've done. Deaths from heart 
attacks and strokes have fallen more than 60 percent--60 
percent. A wonderful colleague like Mark Kirk could make it up 
the steps of the Capitol when he was sworn in for his comeback 
into the United States Senate because of his grit, his verve, 
and the medical science behind him.
    This is not only for a member of the United States Senate; 
it's for all Americans.
    HIV/AIDS--we remember, Dr. Fauci, when the crisis came. We 
were here when a little boy named Ryan White testified. He was 
kept isolated in his own class in school because nobody would 
talk to him. HIV/AIDS, thanks to your work and the brilliant 
scientists, are no longer a death sentence.
    And for the children of the world in our own country, 
children with the most common childhood leukemia have a 90 
percent chance of surviving.
    What a phenomenal story.
    Dr. Varmus, you were the Director of NIH. You go to Sloan-
Kettering. You have one of those cushy, full professorships 
that most people dream about. You come back to head up an 
institute. You announce that cancer rates are down 12 to 15 
percent across the board.
    This is just stunning. And yesterday we saw a brilliant 
actress, an esteemed actress take the bold step, announcing the 
bold step where she had a prophylactic mastectomy in order to 
ensure her own survival rate. But she knew her genetic 
situation. She could have decisions, informed consent. This is 
who we are, and this is what we're fighting for.
    I didn't mean to give a speech, but I'm so excited about 
you.
    And I want to say to my colleagues, this is why we have to 
not only--this sequester I think has a very deleterious, 
eroding, and corrosive effect. So I want to do all I can to 
cancel sequester this year, and also cancel sequester for the 
next 9 years, for which you would then fall behind to the tune 
of $19 billion.
    We hope that the other side--we've got support here on the 
other side of the aisle. I worry about the other side of the 
dome.
    Mr. Ryan, in his budget, is sending it to us to work with 
at $966 billion. That's bad enough, but he took all of it out 
of domestic discretionary spending.
    I'm not going to turn this into politics. We want to be 
above politics. But we're going to have to deal with politics.
    I want my subcommittee chairman and the vice chairman of 
this subcommittee to know, I want to work with them, because 
what I see my job as doing is to do all we can to help you be 
you and help you do the mission that the United States of 
America and its people gave you.
    So I'm going to work my earrings off to make that happen. 
And with that, I just wish we could even get more done.
    I'm not going to ask questions. I've taken a lot of the 
time here. I will be interested in the further discussion that 
we're having.
    Senator Harkin. Madam Chairman, thank you very, very much 
for your leadership of this full committee, and not only your 
leadership of the full committee, but your great leadership on 
this particular subcommittee. For all of the input and 
leadership you've given us through all these years, we thank 
you very much.
    Now, we'll turn to Senator Shelby.
    Senator Shelby. Thank you.
    First of all, I want to associate myself with the remarks 
of Senator Mikulski. She said it so well.
    I believe that the top investment we can make in America to 
save lives, to improve lives, for the American people is to 
invest in the NIH. I believe this.
    I'd like to see us double NIH's funding. I know that's hard 
to do, but to at least get on the upward funding trend, not the 
downward trend, of biomedical research in this country is a 
critical first step.
    And I'm saying that because I see the results of NIH 
research, as Senator Mikulski has pointed out, Senator Harkin 
has, and others, Senator Moran.

            RESEARCH AND ITS IMPACT ON THE STANDARD OF CARE

    Having said that, Dr. Collins, I want to get a little 
parochial, if I can.
    Researchers at the University of Alabama in Birmingham, as 
you well know, conducted an important study on very premature 
babies, a study called ``SUPPORT'' from 2004 to 2009 that was 
funded by the National Institutes of Health. Researchers at 
more than 20 sites were trying to determine, as I understand 
it, the proper oxygen levels for these vulnerable premature 
babies by comparing two ranges of oxygen saturation within the 
standard of care at that time.
    It's my understanding that the SUPPORT study has had an 
important effect on clinical care. Dr. Collins, how important 
is research like this that study and ultimately improve the 
standard of care?
    Dr. Collins. Senator Shelby, thank you for the question.
    Very important, indeed. Standard of care reflects what we 
know at the time, and oftentimes, we don't know enough, and so 
it may be a rather broad range of options and physicians and 
other caregivers who are trying to do the best job of taking 
care of patients. And patients who are seeking the best care 
may not be well-served by all, the entire range, of 
opportunities that are called standard of care.
    That was certainly the case for the study of the optimum 
oxygen levels to give to premature babies.
    Senator Shelby. But you learn by investigating and by 
studying. That's the bottom-line.
    Dr. Collins. You're exactly right.
    So, for us at NIH, we invest heavily in these kinds of 
studies. Let me give you another couple of examples.
    Individuals who are going through hemodialysis, and there 
are a lot, sad to say, many of them because of diabetes. There 
has never really been a clear understanding of what the right 
schedule is for hemodialysis, how many times a week, how many 
hours. That's a huge impact on somebody's quality of life, in 
terms of how much time they're spending there. But also, 
quality of life is dependent on how effective the dialysis is. 
So, a study called the Frequent Hemodialysis Network (FHN): 
Daily Trial, that we have been funding, aimed to try to get an 
answer to that. All in the standard of care, everybody in that 
study, is getting the kind of treatment that you would consider 
standard, but we're trying to find the sweet spot, to do a 
refinement of that.
    I could cite you two or three others. This is very 
important and yet we depend upon patient----
    Senator Shelby. It goes to the basis of your research, does 
it not?
    Dr. Collins. Yes, it does. That's what our goal is, is to 
try to be sure that people get the best possible information in 
order to guide their medical care.

       UNIVERSITY OF ALABAMA AT BIRMINGHAM INFANCY CLINICAL STUDY

    Senator Shelby. As you well know, the University of Alabama 
at Birmingham (UAB) received a letter from the Office of Human 
Research Protection (OHRP) about the SUPPORT clinical trial 
that we're carrying out under the auspices of NIH. And the OHRP 
determined that UAB should have informed parents of an 
increased risk of death of their infant by participating in the 
study. But it was my understanding that the risks were unknown 
at the time of the study's commencement in 2004, and there was 
no specific scientific data that existed at the start of the 
study that showed an increased risk.
    Were babies in that study at any greater risk than babies 
not in the study? Do you know?
    Dr. Collins. No, Senator. I don't believe they were.
    Senator Shelby. Okay.

     INSTITUTIONAL DEVELOPMENT AWARDS PROGRAM ELIGIBILITY CRITERIA

    We've talked about the sequester, I'll move on, on that. 
I'm committed to working with Senator Mikulski to see if we can 
plus-up NIH, though.
    Institutional Development Awards (IDeA), we discussed this 
topic a little bit before. I think it's important to recognize 
that the next scientific discovery may come from anywhere. You 
don't really know where. And I believe that institutions that 
do not historically have high NIH grant rates can still 
substantially contribute to biomedical research. And I believe 
we need to give these institutions an opportunity.
    As we discussed before, Dr. Collins, the eligibility 
criteria for the IDeA program is outdated. Both the fiscal 
years 2012 and 2013 Senate Labor-HHS bills included report 
language regarding this issue.
    However, it's my understanding that no significant 
information on the subject has ever been provided to the 
subcommittee.
    Dr. Collins, could you work with us to develop a better 
criteria, eligibility criteria, for some of these institutions 
that really could contribute, if given a chance?
    Dr. Collins. So, Senator, I know time is short, but I'll 
answer quickly. I do agree that it's a wonderful opportunity 
for capacity-building in this competitive program that is known 
by the name of IDeA.
    The Institute of Medicine has been undertaking a study of 
whether the criteria for IDeA and Experimental Program to 
Stimulate Competitive Research (EPSCOR) are in fact in need of 
revision, and we expect that report to be released fairly soon. 
It would be a good time then to have a conversation with you 
and others about this issue.

                    BREAKTHROUGHS IN CYSTIC FIBROSIS

    Senator Shelby. Let's talk about, if we could, the 
breakthroughs in the research that has been done in cystic 
fibrosis over the years. We've talked about this before, and 
there's been some breakthroughs there.
    Would you highlight some of them, and how we're doing in 
that area?
    Dr. Collins. It's an area of enormous excitement. My own 
research lab back in 1989 played a role in collaborating with 
another group in Toronto in discovering the gene for cystic 
fibrosis. And now, just in the last couple of years, the really 
exciting fruits of that in terms of drug therapy have emerged 
with one drug called Kalydeco now approved in record time by 
the FDA, which shows dramatic responses from individuals who 
have a particular misspelling of that cystic fibrosis gene.
    Unfortunately, only about 4 or 5 percent of cystic fibrosis 
patients are in that category. But there's great excitement 
because of phase II and phase III trials now being conducted by 
Vertex on two new compounds, which should be actually quite 
useful for 90 percent or more of people with cystic fibrosis.
    This all builds upon NIH research that's been done over the 
decades. It's a wonderful collaboration with the Cystic 
Fibrosis Foundation in interaction with the company called 
Vertex. The National Heart, Lung, and Blood Institute, which 
Dr. Gibbons directs, has funded a lot of this effort through 
the years. It is a great success story, and one that we hope to 
replicate for lots of other diseases.
    Senator Shelby. Thank you for sharing it with us.
    Thank you, Mr. Chairman.
    Senator Harkin. Senator Cochran.
    Senator Cochran. Mr. Chairman, I'm pleased to join you in 
welcoming our distinguished panel of witnesses today.
    Dr. Collins, we appreciate your being here again and also 
coming out into the countryside where we live and work.
    Dr. Collins. I enjoy that very much, Senator.
    Senator Cochran. We appreciated the honor of your visit to 
Mississippi.
    And it might interest you to know that just recently, there 
was an announcement from the Blair Batson Hospital for Children 
in Jackson, Mississippi, where you were, by a Dr. Hannah Gay, 
who reported a functional cure of a child who was born HIV 
positive. And this is news that's getting around the world now 
and is attracting attention again to the distinction that 
Mississippi has for people like Dr. Arthur Guyton, who wrote 
many of your textbooks, and others who have pioneered in 
research in different areas.
    So we look forward to supporting the work that you do, and 
we hope we'll be able to provide some seed money or incentive 
grants, funding to ensure that we continue to embark upon 
daring and innovative approaches to dealing with our health 
problems in America.
    Thank you.
    Senator Harkin. Senator Boozman.
    Senator Boozman. Thank you all, and thank you for being 
here. I really do want to compliment you all as a group. Your 
efforts, your work, your advocacy really has changed the world, 
and we appreciate your efforts very, very much.
    There's a lot of things that the Government possibly, we 
could argue, doesn't need to be doing. I think what you all 
represent is something the State of Arkansas, our communities, 
can't do individually, and so we do appreciate the work that 
you do.

                     PUBLIC ACCESS TO NIH RESEARCH

    One thing I'd like to ask about, we have to make some 
significant decisions here. The agencies have to make some 
significant decisions. As we have research that is publicly 
funded, generally, we allow that research to be made available; 
is that correct?
    Dr. Collins. Yes, we strongly support the need for that. If 
the public has paid for the research, the public should have 
access to it. I think NIH, it's fair to say, has taken the lead 
in trying to make sure that that kind of access to information 
happens in a timely fashion.
    The recent suggestion, by the Obama administration, is that 
this kind of policy should be applied broadly across all of the 
agencies, and I think many are looking at NIH's model as 
something to replicate in other parts of the Government as 
well.

                      DUAL-USE RESEARCH SAFEGUARDS

    Senator Boozman. And again, I appreciate that and agree 
wholeheartedly. And I'm glad that that is the policy.
    Can you envision a reason not to do that in some cases?
    Dr. Collins. Perhaps you're talking about circumstances 
where the data that's being generated might in fact create some 
risk to the public if it fell into the wrong hands.
    I'm going to ask Dr. Fauci to comment on this, because this 
often falls in the category of areas that might be amenable to 
bioterrorist misuse, and we've certainly been engaged in those 
conversations. And Dr. Fauci has had the lead in many of them.
    Tony?
    Dr. Fauci. Yes, thank you for that question.
    It is a delicate balance, particularly when you do what is 
called dual-use research of concern, where the public health 
imperative for understanding whatever process you're looking at 
is quite important. Yet you're concerned with two things.
    One is the deliberate misuse of things that have to do, for 
example, with potentially pathogenic microbes that could be 
used in a bioterror situation or the inappropriate and careless 
use of that information by people who are not qualified. It 
transcends all areas of research, but it's particularly acute 
when you're dealing with the study and perhaps even creation of 
a microbe that might, in fact, be an issue.
    Having said that, we tend, unless there's a really very 
good reason, to be as open and transparent as possible, because 
the default rule--and we're careful about that and not 
careless--is that not allowing knowledge to be generally spread 
throughout the scientific community has more deleterious 
effects than the risk of having something being used in a 
deleterious way accidentally or deliberately by others.
    So, it goes along with the concept that Dr. Collins 
mentioned, that we have been the leaders and we continue to 
stress the open nature of scientific information.

             CLINICAL TRIALS AND VOLUNTEER CONFIDENTIALITY

    Senator Boozman. Okay. And as far as we can always put 
safeguards and a lot of research sometimes involves people and 
things like that. I mean, we can always put the safeguards in 
to protect, so that we are able to release the data without 
jeopardizing people. Is that----
    Dr. Collins. So, I think there, you're getting at the issue 
about privacy and confidentiality for people who are part of 
clinical trials that NIH supports who have been willing to 
volunteer to take part in a study and who are happy to be part 
of that, but don't want all of their medical records to be 
accessible by everybody on the planet.
    Yes, we take that with great seriousness and make every 
effort, and I think we've been quite successful, to keep that 
information only in the hands of those who have a need to know 
as part of the research project.
    Senator Boozman. Again, thank you all for being here. I 
really do appreciate your efforts and, as a new member on the 
panel, I look forward to working with you in the future and 
supporting your efforts. Thank you.
    Dr. Collins. We look forward to that, too. Thank you.

        IMPACT OF THE BRAIN INITIATIVE ON NEUROLOGICAL DISORDERS

    Senator Harkin. Thank you, Senator.
    We'll start a second round here. I wanted to follow-up a 
little bit on the BRAIN Initiative, Dr. Landis and Dr. Hodes, 
because when I first heard about this bump-up in this new 
initiative, we were talking about it and someone said, well, 
how is this going to affect all the research on Alzheimer's? I 
don't know.
    There's a report that came out that said that the total 
cost of care for individuals with Alzheimer's disease will soar 
from $172 billion in 2010 to more than $1 trillion by 2050; 
that Medicare costs are increasing more than 600 percent from 
$88 billion today to $627 billion in 2050, if we keep on the 
same trajectory.
    So, tell me about this BRAIN Initiative. What's it going to 
do in terms of the research we're doing on Alzheimer's, or is 
this something separate and apart?
    Dr. Landis. So, let me talk about the BRAIN Initiative and 
the promise of the BRAIN Initiative, and then I'll turn it over 
to Dr. Hodes to address the issue of Alzheimer's.
    The long-term goal of the BRAIN Initiative is to be able to 
develop treatments for patients across the broad range of 
psychiatric and neurological disorders, and I'll give you a 
very specific example.
    In the case of Parkinson's disease, one of the major 
advances has been the development of deep brain stimulation 
where electrodes are planted in particular regions bilaterally 
of Parkinson's patient's brains in the midcourse of the 
disease.
    This stimulation, kind of like a brain pacemaker, can 
transform the quality of life of those patients. They can move 
freely. They're much more active. They would, in some cases, 
not even appear to have Parkinson's.
    That effect wears off with time. This stimulation is very 
crude. It's an electrode that is influencing the circuit 
behavior. If we understood more about how the circuits work 
that control movement, that control compulsions, that control 
speech, we would be able to design much better interventions, 
electroceutical interventions--not pharmaceutical, but 
electroceutical--that would rebuild those circuits in a much 
more effective way.
    Deep brain stimulation is now being used for obsessive-
compulsive disorder. It's being used for intractable 
depression. And in each case, the electrode is going in a 
different part of the brain, but it's the same crude 
stimulation.
    So, just by analogy to Parkinson's, if we understood the 
circuits for obsessive-compulsive disorder or intractable 
depression, we would be able to come up with much more 
effective ways to change the circuitry to ameliorate those 
diseases.

         IMPACT OF THE BRAIN INITIATIVE ON ALZHEIMER'S DISEASE

    Senator Harkin. That's all well and good, but we have a 
crisis on our hands with Alzheimer's, a real crisis. And I'm 
wondering--this is well and good. I'm all for that. But I'm 
concerned that we're not doing enough to really focus more 
research on, if you can just put off the onset of Alzheimer's 
for 5 years, that would save so much money.
    So tell me how this affects Alzheimer's research?
    Dr. Hodes. Thank you for the opportunity to comment on 
this.
    As noted, the cost, the public health and human suffering 
cost of Alzheimer's, is huge. In addition to the public health 
demand, of course, what is important is for us to assess 
scientific opportunity and quality of science. It's one thing 
to recognize a problem. Now we have a responsibility to address 
it in the best possible way.
    And the most responsible way to do this at this point, when 
we don't know what ultimately would be the successful approach, 
is to invest across a spectrum from those basic discovery on 
through translation.
    So, we have some enormously important and innovative 
clinical trials happening. In the last year, for the first 
time, we're able to identify people at enormously high genetic 
risk, in whom we can find, by bio-imaging, signs of disease 
years, even decades, before onset and begin for the first time 
to treat them.
    So, we have new opportunities we didn't have before.
    But having said all this, we still have an opportunity, 
and, in fact, an obligation to better understand the cellular 
and molecular underpinnings, so that we can continue the effort 
to generate new generations of investment. That is where this 
BRAIN Initiative happens.
    It's clear that Alzheimer's disease is not a disease of 
just a single cell or even a single cell type. It involves 
defects in the communications between cells, and the more we 
understand, in the sense of what the brain will tell us, the 
better we can intervene to the specific things that are going 
wrong in Alzheimer's disease.
    Senator Harkin. So, again, you're both telling me that this 
BRAIN Initiative does have an impact on Alzheimer's research.
    Dr. Landis. Yes. So, one very surprising finding of the 
last couple of years has been that there is abnormal electrical 
activity, almost like mini seizures in the brains of 
Alzheimer's patients. It's not clear the extent to which that 
abnormal activity influences the course of the disease.
    But if we knew better how to modulate activity in circuits, 
and which were the right circuits, we could potentially 
intervene in those electroform activities in Alzheimer's 
patients and potentially have a very positive effect on their 
quality of life.
    Dr. Hodes. It's well-described, and in fact, it comes back 
to another point made, the concern we have about not being 
overly conservative, that we don't fail to take advantage of 
truly bold and innovative new approaches. This is an example, 
at the same time we're doing the best we can to translate what 
we think is the best information about cause and potential 
interventions for Alzheimer's, we still have an obligation to 
make sure we examine broadly the kinds of information which 
will tell us about whole new approaches that may be, in the 
end, the best or most definitive solution.
    Senator Harkin. Thank you all very much.
    Senator Moran.

                         CARDIOVASCULAR DISEASE

    Senator Moran. Mr. Chairman, thank you.
    Dr. Gibbons, cardiovascular disease is the leading cause of 
death in the United States. It's certainly a driver of 
healthcare expenditures. I'm told it costs the U.S. consumer, 
the patient, $312.6 billion a year.
    Sunday's New York Times had an article on an NIH study that 
is using genetic sequencing to find factors that increase the 
risk of heart disease beyond the usual suspects of high 
cholesterol, high blood pressure, smoking, and diabetes.
    Would you tell us more about that study?
    Dr. Gibbons. Well, thank you for that question. This is one 
of the great success stories, I think, in biomedical research, 
where discovery science related to the pathways that determine 
low density lipoprotein (LDL) cholesterol, the bad cholesterol 
metabolism, led to Nobel Prizes for Brown and Goldstein.
    There was a great public-private partnership that led to 
the identification of a target that would lower LDL 
cholesterol. That led to a drug, Statins. I suspect, for those 
of us over 50, a lot of us in this room may even be on one.
    That was a breakthrough drug that's transformed medicine. 
Indeed, that public-private partnership is one that is critical 
to advancing medicine.
    The question now is that although we have studies that show 
the remarkable improvements of having patients on statins, 
unfortunately, there are still patients on statins who have a 
heart attack every few moments in this country. So, that tells 
us there's still unfinished business. There's still some 
unsolved mysteries.
    That article related to us continuing to try to figure out 
those patients where we don't really understand all the risk 
factors, all the predictors of who's going to have a heart 
attack. And as you saw in that article, a devastating impact on 
a whole family that we really couldn't explain, but that's 
where we have these unprecedented opportunities.
    With new technologies, we're able to sequence parts of the 
genome and probe into why is this family so different and 
distinctive in a way that's really devastating to it? We're 
hopeful that that will identify new pathways that will tell us 
more about the risk of heart attacks. That may recapitulate 
that story we just had with LDL cholesterol.
    That's the promise of the future. Those are the investments 
we need to make now for those breakthroughs tomorrow.
    Senator Moran. Is there enough research to give us a clue 
as to what those other factors may be?
    Dr. Gibbons. Well, there's a lot of promise. Perhaps one 
example, a sort of a harbinger of that, relates to a molecule 
called proprotein convertase subtilisin/kexin type 9 (PCSK9), 
in which a similar sort of strategy delved into the molecular 
determinants of, again, a group of families, a group of 
patients that had an abnormal level of LDL cholesterol. The 
probing use of modern genomic technologies unveiled this new 
gene in this other pathway that told us another potential 
target.
    And indeed, as part of the recapitulation of that public-
private partnership in which discovery science translated into 
drug development, a new drug has been developed that targets 
that same sort of pathway. That's now in the midst of clinical 
trials, to see if on top of statins or in a complementary way 
going after this new target can actually give us more bang for 
the buck.
    Similarly, one of the things that we're learning is that 
although you have that bad cholesterol, what we're also 
appreciating is not just that clogging of the arteries but it's 
also the activation of the body's immune system that sort of 
turns against the blood vessel and inflames it just like your 
allergies flare up your sinuses.
    In that sense, the blood vessels were inflamed.
    So, what we're now looking at is new targets that may not 
only target the cholesterol level but that inflammatory 
response that also promotes heart attacks. That's where some of 
the great breakthroughs, I believe, are coming. And indeed, 
we're funding a study that's looking at tackling that 
inflammation part of the story, to see if we can make the next 
breakthrough.
    Senator Moran. I wish you great success.
    Dr. Gibbons. Thank you.

                       ACCESS TO CLINICAL TRIALS

    Senator Moran. Dr. Collins, I have very little time left, 
but as people know, Kansas is a very rural State. I have 
concerns about clinical trials.
    And in order, I assume, for a clinical trial to have 
validity, it takes a wide range of demographics and 
characteristics. And it seems to me there are barriers toward 
some people joining clinical trials based upon geography, age, 
other demographic and personal characteristics, perhaps fear of 
Government research, lack of awareness of clinical trial 
availability.
    What can I do--what is NIH doing--but what can I do as a 
Senator in caring for Kansans to make certain they are aware of 
the opportunity to participate in clinical trials and 
potentially improve their health and save their lives?
    Dr. Collins. It's a great question. NIH is by law, in our 
clinical trials, required to be sure we are reaching out to a 
diverse population. We track that carefully, and all the 
individuals who review clinical trial grant proposals and the 
program staff who follow those, make sure that we have a 
diversity of population involvement in the studies, whether 
it's heart disease, diabetes, cancer, whatever.
    But of course, we are dependent upon public knowledge about 
the ability to be part of such trials, and I appreciate your 
question very much in that regard.
    There is a Web site called clinicaltrials.gov, which is 
heavily utilized in every clinical trial that we support. And 
most of the ones supported by industry are also listed on that 
site. You can search it very readily to identify a particular 
condition, in some particular part of the country, where a 
trial is currently enrolling patients and what's the nature of 
that trial. And people can decide if they want to take part.
    Getting the word out about that would be a wonderful thing 
to do, and I appreciate very much your suggestion of helping 
with that. We would welcome that.
    Dr. Landis. If I could just add something. The National 
Institute of Neurological Disorders and Stroke (NINDS) recently 
set up a phase II clinical trials network called NeuroNEXT, 
with 25 sites across the country. One of them is at the 
University of Kansas Medical Center, and we are hoping to 
incorporate into the clinical trials undertaken by that network 
telemedicine, which would enable, for example, for stroke where 
patients at a distance to be seen by and treatment recommended 
or randomization recommended through the main NeuroNEXT site.
    So we're very interested in engaging in this with you.
    Senator Moran. I like that answer. Thank you very much.
    Senator Harkin. I'm sure you do.
    Senator Shelby.

            PROGRESS OF THE PROVOCATIVE QUESTIONS INITIATIVE

    Senator Shelby. Thank you, Mr. Chairman.
    Dr. Varmus, last year, we discussed a new initiative that 
you started to answer what we call provocative questions in 
cancer research.
    When budgets are constrained, we need, I believe, out-of-
the-box ideas to answer some of the big research questions that 
could lead to the next breakthrough. You're in the forefront 
and I think your project is an innovative approach to define 
some of the unanswered questions in cancer research.
    Would you share with the committee this afternoon some of 
the progress you've made on this initiative, and what 
provocative questions have been awarded grants, or where are 
you?
    Dr. Varmus. Thank you, Senator.
    Obviously, this program is only a little over a year old, 
so we don't have results yet, but we do have results of 
advertising for applications.
    The first year, we chose 24 questions, the kinds of 
questions that were raised vary dramatically from questions 
about why people with profound obesity have increased risk of 
dying of certain kinds of cancer. There were questions about 
why drugs that are not all that effective in many 
circumstances, like chemotherapy for certain kinds of cancer, 
are remarkably effective for testicular cancer and certain 
other rare cancers.
    We've asked questions about behavior. Why do people still 
smoke when they know how bad smoking is?
    There were 24 questions of those similar dimensions chosen. 
We've received 750 applications to try to answer those 
questions. All 24 questions were addressed by at least several 
of the applications.
    Funding is short. We were able to fund slightly over 50 
applications. The funded grants address most, but not all, the 
questions.
    We then revised the questions, included some new ones that 
had come from recent workshops. We reconfigured some questions 
that we thought, perhaps, could be addressed more effectively 
if we rephrase them. And we received, this year, so far, 
several hundred applications.
    So, there is obviously a pent-up need. How good the 
applications are? It's hard to say. Many received very high 
marks from the reviewers. How well they'll do, that's always a 
crapshoot, frankly. And we won't know for a few years how well 
this works.
    We have gotten, of course, a lot of feedback from our 
community. They like the idea that we're not dictating the 
questions. The questions are coming from a community effort.
    We're trying to support the community at a period when 
morale is poor because of the low success rate. We're trying to 
say, we are partners in trying to develop the kinds of 
questions we think this community should answer, the kinds of 
risk we should be taking. We see this as one of the ways, not 
the only way, by any means, in which we try to cope with 
sequestration, with reduced opportunity to get grants.
    Thank you for the question.

                      AUTOIMMUNE DISEASE RESEARCH

    Senator Shelby. Dr. Collins, I'd like to talk about 
autoimmune and the research there.
    The NIH and various investigators have come a long way in 
dealing with autoimmune research, because it goes to the basis 
of so many things. In particular, where are you today in trying 
to deal with lupus? We've talked about this before and there 
have been some breakthroughs there. And where do you think you 
might go?
    Dr. Varmus, do you want to get into that?
    Dr. Varmus. No, thank you.
    Senator Shelby. Okay, okay. Any of you could. Dr. Collins.
    Dr. Collins. Actually, I'm going to ask Dr. Fauci to get in 
on this, because he's a card-carrying immunologist, and he can 
really talk about this.
    Senator Shelby. Doctor, thank you very much.
    Dr. Fauci. It's a pleasure. Thank you for the question. One 
of the approaches that we and other institutes are taking with 
regard to autoimmune diseases is making some significant 
advances in the field of what we call immune tolerance.
    Immune tolerance is to train the body's immune system not 
to respond inappropriately against certain antigens. In the 
case of lupus, those are self-antigens, and that's the reason 
why they call it autoimmunity.
    Several years ago, we established an immune tolerance 
network that was originally established to look at ways that we 
could prevent the rejection of transplants. We've expanded that 
now into the study of a number of other diseases that are 
clearly characterized by autoimmune phenomenon, including type 
1 diabetes, certain allergies, as well as very important 
rheumatologic diseases like systemic lupus erythematosus.
    So, it really is, again, another, I think, beautiful 
example of studying the fundamental, basic research on the 
immune system that is now being translated into therapies to 
suppress inappropriate immune responses.

                      COLLABORATION WITH INDUSTRY

    Senator Shelby. Dr. Collins, do you want to talk about any 
therapies that are coming along?
    Dr. Collins. I appreciate the chance to respond. I just 
want to mention one collaboration that's underway right now, 
which is actually quite groundbreaking and, I think, 
innovative. And that is something called the target validation 
consortium, which is a group that has come together between 
industry and NIH to try to identify amongst a wealth of new 
potential drug targets that have emerged from basic science 
studies, things like genomics and immunology, which are the 
ones that are actually going to work, because the industry 
wants to put their bets on something that's actually going to 
lead to a drug that's safe and effective.
    So, working with industry, we've identified four areas of 
great opportunity. One of them is autoimmune diseases--
rheumatoid arthritis, lupus, Crohn's disease. The others are 
type 2 diabetes, Alzheimer's disease, and schizophrenia.
    And right now, we're in the midst of the design phase of 
this effort with 10 companies that have agreed to sign up. This 
is at the very high level with the companies in the design 
phase. And, if it looks promising in the next couple of months, 
we're likely to see a major new kind of collaborative effort 
where industry and NIH agree that this is actually open access, 
precompetitive information, we can all work on this together. 
Let's find the most appropriate targets and then turn industry 
loose to find that next generation of drugs.
    Senator Shelby. Thank you very much.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator.
    Senator Mikulski.
    Chairwoman Mikulski. Thank you.
    You know, if we just stuck with the A words, it would keep 
us all very busy for three lifetimes, from arthritis to 
Alzheimer's to allergies and so on.
    So it's great to hear both sides of the aisle talking about 
the same thing.
    I want to come back to Dr. Fauci.
    Senator Shelby, I was also going to raise the question of 
autoimmune. I'm glad that you did.

                    MULTIPLE DRUG-RESISTANT BACTERIA

    But I want to raise, Dr. Fauci, with you the superbug 
problem, because this is a significant issue. And I'd like to 
know where are we heading with our research? What are your 
thoughts and recommendations? Is it also recommendations that 
should be implemented in more quality initiatives in hospitals, 
like the Pronovost checklist?
    Could you share with us, because this is a really 
significant issue that we're hearing from both constituents and 
hospitals?
    Dr. Fauci. You're very correct, Madam Chairwoman, that the 
issue of multiple drug-resistant bacteria, and we'll just 
concentrate on them now as opposed to other types of resistant 
microbes, are a very important problem in the United States and 
worldwide, and a growing problem.
    If you look at the number, up to a million hospital-
acquired infections, of which a rather substantial proportion 
of them are resistant to the standard drugs leading to the 
unnecessary deaths of people in the hospital. This is a major 
public health issue.
    There are two approaches to that. One is a public health 
approach, which really relates to some of the recommendations 
of our own Centers for Disease Control and Prevention, and the 
other is the basic research approach, which we at the NIH are 
taking.
    The public health approach is on things like isolation, 
identification of people when you transfer from one hospital to 
another to make sure you let people know that you're 
transferring somebody with a resistant microbe. You know, we 
had a problem at the NIH a-year-and-a-half ago that we luckily 
solved. One of the things we learned is that you have to make 
people aware of when you're dealing with a drug-resistant 
microbe in a patient. Washing hands, all kinds of isolation 
procedures.
    But the real core problem, that we've been intensively 
addressing over the last couple of years, is the lack of a 
really robust pipeline of new drugs that could take the place 
of the drugs that are now--to which the microbes are resistant.
    So, if you look at how things work with the NIH and how we 
interdigitate with industry, we generally do the fundamental 
basic concepts. We make the initial discovery, proof of 
principle, then maybe go into a phase I or maybe even a phase 
II trial. Whereas industry, which is responsible for making the 
product, generally meets us halfway or so.
    The risk, economically, for a company to invest a lot of 
money into the development of new antibiotics is such that we 
have to help what we call de-risk them. In other words, pushing 
the envelope closer to getting better understanding of 
mechanisms of drug resistance, how you can target on a microbe, 
new targets for drugs to make it easy for the company to get 
involved in providing us with this robust pipeline.
    I think that's going to be a very good approach, because 
we've actually just recently established a new clinical trial 
network for multiple drug resistant bacteria in our hospitals.
    So again, to reiterate, it's a very serious problem, and at 
the NIH, we're taking it very seriously.
    Chairwoman Mikulski. Well, first of all, that's promising 
to hear. And we also have to look at the role of the Centers 
for Disease Control and Prevention (CDC) here.
    I know, Mr. Chairman, you'll be holding a hearing on that 
in a matter of days.
    But, Dr. Collins, is that, I know it's not the--but is this 
the methodology you're talking about where you work with the 
industry on what, I used the term precompetitive, or whatever 
is the right legal term. But, really because there was so much 
risk in some of these areas, the private sector is not going to 
get into it, and we do create our own valley of death, because 
we don't go far enough. Is this one of those endeavors?
    Dr. Collins. You're quite right. The valley of death in 
this situation, that Tony was just describing, can be broad and 
yawning because the far side of it is even further away, 
because of companies' lack of really commercial motivation to 
get engaged.
    You develop a drug for highly resistant organism. People 
will say, you shouldn't use that drug, except in very specific 
circumstances. Otherwise, you'll use it up and it won't be any 
good anymore. So the market is very small.
    Chairwoman Mikulski. And people want cheap antibiotics, 
too.
    Let me get to another thing before my absolute time is up. 
I know you've talked about Alzheimer's and many issues.

                                 AUTISM

    I want to talk about autism, another A word. This is really 
another epidemic that has hit our family, our family of fellow 
Americans.
    Just about in every school, almost now in every extended 
family, there is a child facing one of the aspects of the 
spectrum of autism.
    Could you share with us where we're heading with research 
on this? Is this something we should also look at beefing up? 
Could you share with us where we are on this? Whoever is 
appropriate, for anyone.
    Dr. Collins. I'll say one sentence, and then ask Dr. Landis 
to say more.
    One area that is making progress is to understand genetic 
contributions to autism. We now think maybe 15 to 20 percent of 
cases are the result of new misspellings in DNA that were not 
present in either parent but appear in that child.
    Almost always that seems to be in a pathway that involves 
synapses in the brain. That seems to be the common thread here 
about what's wrong in autism. The connections between nerve 
cells aren't forming in the way that they normally should.
    But there's much more to say here.
    Dr. Landis. So, I think that is in fact one of the most 
promising avenues, and there are a number of genetic studies, 
which are looking at trios where the parents are normal and the 
child has autism, and using advanced genetic techniques, 
identifying the genes that affect the gene or genes 
responsible.
    What's particularly interesting is, as the number of genes 
go, just as Dr. Collins said, these are genes which act on the 
development of connections and the development of the synapses. 
Of most interest is the fact that the same genes are being 
identified in epilepsy and schizophrenia and a number of other 
neurodevelopmental disorders.
    It will be very important to figure out, first of all, what 
those mutations do to development, but also why the phenotype 
of patients, each of which has the same mutation, is so 
different. So, very interesting, very interesting clues.
    Dr. Collins. Just to quickly point out also that despite 
the advances in genetics, we know that's not at all the whole 
story. There must be profound influences that are based upon 
other environmental events, some of them probably happening 
during pregnancy. There's a great deal of intense effort to try 
to understand that as well.
    Chairwoman Mikulski. Thank you very much, and just thank 
you for what you do every day. Thank all the 18,000 people at 
NIH and the extramural people.
    Senator Harkin. Thank you, Senator.
    Senator Boozman.

                       INTER-AGENCY COLLABORATION

    Senator Boozman. Thank you, Mr. Chairman.
    Dr. Collins, I'd like to ask about, and really use two very 
different examples, about the ability of NIH to perhaps work 
with the other agencies.
    I'm on the Veterans Affairs Committee. Everybody at the 
panel here is very, very concerned about veteran suicide. 
They're working really hard to try and do something under a lot 
of pressure to perform.
    One of my concerns is the easiest thing to do, if you have 
a caseload that is bigger than you can handle, there is a 
tendency to overmedicate. I think that is a problem.
    But aside from that, again, the ability of your agency to 
come in, recognizing there is a problem. They're spending a lot 
of money in trying to solve the problem.
    If there's an effort that we could collaborate, and you all 
use the unique expertise that you have to help with that 
problem.
    The other thing is I was at the toxicological lab in Pine 
Bluff of the FDA. And another very differing example is the 
nanotechnology, which the FDA is concerned about, we're all 
concerned about. What really helped me grasp it was the fact, 
when you look up, you can think of infinite upness. With 
nanotechnology, you're really dealing with infinite smallness, 
which is amazing.
    And as you guys know better than anyone, as you get very 
small, then everything changes.
    But it is something that offers tremendous potential. One 
of these things that truly can change the world by helping us 
not use as much resources by better lubrication, things like 
that where things don't wear out, these conflict minerals and 
things.
    So is there the ability for you all to step in and help FDA 
deal with those kinds of problems and support the work at the 
toxicological lab?
    Dr. Collins. Senator, those are two terrific questions.
    With regard to suicide, I think all of us are deeply 
concerned to see what the rates are of suicide, especially in 
returning servicemen. We've been working, actually, closely 
with the Department of Defense in a program called Study To 
Access Risk and Resilience in Servicemembers (Army STARRS), 
which has enrolled more than 100,000 recruits, trying to 
identify what, if any, kind of warning signs have been missed 
in the past that could give us a better chance to intervene 
before suicide occurs.
    This is a close collaboration between our National 
Institute on Mental Health (NIMH) and the Department of 
Defense. And there is an interaction there also with the 
Department of Veterans Affairs (VA) because of their very 
strong interest in the same issue.
    With regard to your question about toxicology----
    Senator Boozman. I'm sorry, the next step again would be 
dealing with people that are actually at that point.
    Dr. Collins. Yes.
    Senator Boozman. That might be helpful also.
    Dr. Collins. Indeed. And of course, suicides are more 
common than homicides in this country, and there is a great 
deal of effort to try to understand ways to identify risks.
    Obviously, for people who have not been in the military, if 
you look at what are the risk factors for suicide, bipolar 
illness is a very major correlate, because when people with 
that condition go into a deep depression, that is often where 
the risk is highest.
    Senator Boozman. And heavily medicating in some cases makes 
it worse or better?
    Dr. Collins. I think the experience has been that proper 
medication, with Lithium and other efforts, can be lifesaving. 
Reading books by Kay Jamison, for instance, would emphasize 
that, as someone who has written about it and who has 
experienced it herself.
    But there are challenges in terms of getting it just right, 
and we are still working on new interventions that will be more 
effective than what's currently available, because most of the 
drugs have been around quite a long time, and it's time to see 
if we could find some new answers. This notion of working with 
industry to find new targets comes to mind.
    With regard to your question about toxicology and 
nanotechnology, Peggy Hamburg, who's the commissioner of the 
FDA and I jointly run a leadership council that tries to 
identify ways that our agencies can work closely together, 
particularly helping FDA with identifying new regulatory 
science opportunities, and FDA helping NIH identify areas where 
more science is needed and where our investigators can be 
better prepared to conduct trials that FDA can then review.
    Nanotechnology is a very interesting example, because there 
is a question about the safety of nanotechnology applications 
for human health. Given that this isn't exactly a simple area, 
all different particle sizes, all different kinds of compound 
constitution, NIEHS, the National Institute of Environmental 
Health Sciences, has a research program on this. And we are 
part of the National Nanotechnology Initiative.
    We mentioned earlier the BRAIN Initiative, trying to come 
up with ways that could sample these 86 billion neurons. If 
we're going to get anywhere near that, we're going to need 
nanotechnology tools to do so. So, it is very much an 
appropriate question. To be sure, we're working together.
    Senator Boozman. Thank you, and again, thanks for all you 
do.

             NIH/CDC/FDA COLLABORATION ON H7N9 (AVIAN FLU)

    Senator Harkin. The last question Senator Mikulski asked, I 
think Dr. Fauci, the question about the superbugs. One last 
thing was that in meeting with Dr. Frieden of the Centers for 
Disease Control and Prevention a few days ago, talking about 
this new avian flu.
    You've been down that road before, Dr. Fauci.
    So, a new one has popped up. This one is known as H7N9, and 
there have been 131 confirmed cases by the World Health 
Organization (WHO), 32 deaths. There has been no evidence of 
sustained human-to-human transmission.
    But the problem is, as I understand it, that there is 
obviously a very high death rate, but the birds that are 
infected have no symptoms. And so again, how are you 
correlating research on this along with the CDC?
    Dr. Fauci. Thank you for that question. It's a very good 
example of very nice collaboration and coordination between the 
different agencies of HHS, not only CDC and NIH, but also FDA.
    So, where we are right now, there are actually 35 deaths. 
There were three deaths that were reported yesterday and today. 
So it's 131 cases and 35 deaths.
    We are approaching this exactly the same way as we 
approached the H5N1 that started in 2003 that we discussed 
before this committee many times that's still smoldering, as 
well as the 2009 H1N1 real pandemic that we had. That is 
virtually within days of noticing this, the virus was isolated, 
sequenced, sent to the CDC with the sequence, who are then, by 
reverse genetics, created what we call seed viruses for the 
development of a vaccine.
    A seed virus is a virus that we make that we can then 
distribute to the different pharmaceutical companies that we 
have contractual relationships with for our regular seasonal 
flu. They are already starting to make what we called pilot 
lots to determine whether or not we're going to be able to test 
these.
    The NIH, which is our main responsibility, has already 
developed and designed clinical protocols to test what is the 
right dose, do you need an adjuvant or not, do the doses differ 
between children, adults, elderly, and pregnant women. I've 
seen the trial designs and they are ready to go. As soon as the 
pilot lots are up, which will likely be by the end of June, the 
beginning of July, we'll start clinical trials.
    Now, we may not ever have to use the vaccine. But the 
important thing is, we'll get those lots, we'll know how to use 
it. So, if it does begin to have what you mentioned correctly, 
sustained human-to-human transmissibility, which it does not 
have right now, if it does, then we can scale up and have a 
vaccine available.
    We've also done many of the sequencing to look for genes 
that might predict whether it's sensitive or resistant to the 
neuraminidase inhibitors, the ones we commonly use, Tamiflu and 
Relenza. Fortunately, they appear to still be sensitive to 
those antivirals.

                      UNIVERSAL INFLUENZA VACCINE

    Dr. Collins. So, Tony, wouldn't it be great if you didn't 
have to do this every time a new strain appeared? Do you want 
to say something about progress to get a universal influenza 
vaccine, because that's quite exciting? We might not have to 
have this conversation in 10 or 15 years.
    Senator Harkin. How close are we to that?
    Dr. Fauci. Well, you know, I can't give you a time, but I 
can tell you we're clearly closer than we were a year or two 
ago, and let me explain why. Because, what Francis is alluding 
to, for people who didn't hear it, is the universal flu vaccine 
that you could actually give to someone and then it would be 
inducing protection against a wide range of influenza strains, 
from season to season, and even from pandemic to pandemic.
    What was discovered a few years ago by NIH grantees, that 
there's a part of the protein that's the main protein of 
influenza called hemagglutinin that is shielded from the immune 
system recognizing it.
    So, when you get infected, Mr. Chairman, or you get a 
vaccine every year, your body's immune system doesn't recognize 
a part of that protein that doesn't change from strain to 
strain. The part that changes is called, well it looks like a 
mushroom, it's got a head and it's got a stalk. The part that's 
the protective part is the head, and it changes from season to 
season. And when you have a pandemic, it changes a lot.
    So, if you make an immune response, you're good for that 
season, but you're not good for the next season when it 
changes. Whereas on the stalk of the hemagglutinin, there is a 
sequence, a particular protein, that doesn't change from flu to 
flu. So, we've now figured out a way, how to show the immune 
system that particular protein, so that it makes an immune 
response against it. We've now shown it in animals, mice, 
ferrets, and monkeys, that when you show them this protein, 
they make antibodies against the wide array of influenzas.
    We started phase I trials, showing that it's safe, and it 
induces a response. We're getting ready to go into a phase II 
trial.
    So, I can't give you a year when we're going to have it, 
but we're a heck of a lot closer than the last time you asked 
me that question.
    Senator Harkin. I had no idea of that. That's pretty 
encouraging. I mean, just think of the health implications.
    Dr. Fauci. That would be enormous.
    Senator Harkin. It would be huge.
    Dr. Fauci. Right.
    Senator Harkin. And the savings in illnesses, the 
hospitalizations, loss of work, my goodness, plus just knowing 
that you're safe against some of these pandemic flus.
    Dr. Fauci. And you could stockpile. See, that's the thing 
that we can't do. We're always in a yearly race. We find out 
what's going to be circulating, and we race to make a vaccine 
to be ready in the fall to give to people, so they can have it 
for the winter.
    If you have a universal flu vaccine that essentially covers 
it all, you can start making it right now for 2 years from now.
    Senator Harkin. Of course. Keep us informed.
    Dr. Fauci. I will.
    Senator Harkin. That's very encouraging. Especially if 
you've got something that you know dosage-wise you can do for 
children, adults, pregnant women, all the different types of 
people that need this type of a vaccine.
    Dr. Fauci. So, when you come to the NIH, we'll show you 
where it's done.
    Senator Harkin. I will, thank you. That's very encouraging.
    Senator Moran.

                EXPERIENCED AND NEW INVESTIGATOR FUNDING

    Senator Moran. Mr. Chairman, thank you.
    Just a brief question, Dr. Collins. I'd like to have you 
assure me that there are actions in place that make certain 
that both well-established investigators are funded as well as 
incubator-type environments where young investigators can 
thrive and provide great breakthroughs.
    Dr. Collins. Of course, that's very important. It could 
hardly be more important.
    I think the most important resource we have is the talented 
scientists who do the work, and some of them are in mid-career 
and just incredibly at the top of their game, and others just 
getting started with vision and drive and energy.
    The sad story is that all of those groups are taking a hit 
right now. There's nobody getting protected.
    We do what we can, particularly with early stage 
investigators to be sure they have a chance to get started. So, 
we have them, in the way we do our peer review, compete against 
each other. The early stage investigators, they don't have to 
compete in the same pool as far as funding decisions with 
somebody who already has an established lab and a lot of 
preliminary data and a lot of publications, because we want to 
be sure that we're not disadvantaging our future, which are 
these folks that are just getting started.
    But there is no magic here when success rates have fallen 
for everybody to 15, 16 percent. I know we are losing 
significant talent all through the career range of the people 
that we support, from the young to the middle, to those who are 
basically in the cap of their career.

               DECLINE IN THE NUMBER OF NEW INVESTIGATORS

    Senator Moran. You have the statistics--I've never seen you 
not be able to answer a question, so I know you have the 
statistics. Are the numbers of new applicants, individuals who 
have never applied, or organizations that have never applied 
for a grant, is that number changing?
    Dr. Collins. You know, I'm a little concerned to see that 
this year, the numbers seem to be dropping back a bit, and 
that's actually quite troubling. That begins to suggest that 
people are beginning to lose hope. And you can sort of see why.
    When investigators, with this success rate of 15 or 16 
percent, spend most of their time just writing a grant only to 
have it rejected, but then they'd better be writing another 
one, otherwise, their lab is going to close.
    They don't get to do science that much anymore. It's all 
about trying to find the funding from the Government, from 
foundations. I think, after a while, as people begin to burn 
out with that, perhaps we are seeing a fall off in the 
willingness to go through that experience over and over again 
only to see rejection.
    So, I am concerned, as one of the warning signs that the 
community is beginning to be sufficiently disheartened as we're 
going to lose people.
    We have lots of anecdotes about that. It's hard to collect 
precise data about exactly how many investigators have given 
up. We're in the process of trying to do that, but the 
anecdotes are sufficiently numerous that I'm deeply worried.
    Senator Moran. Well, Doctor, I would never contradict you, 
but I find this hearing always a place of hope. And it is one 
of the places within the halls of Congress in which, when you 
leave the hearing, you have a better outlook for what the 
future holds.
    And so I appreciate very much what you and your team, what 
the folks at NIH and those that you fund and support, provide 
something that America desperately needs, something called 
hope.
    And I just would encourage you to let Dina Faddah know that 
there is hope, and tell her that we all encourage her to pursue 
that career in research and science and medicine. And that 
while there's always challenges, the opportunity to provide 
hope to Americans, to provide hope to the world, it's worth the 
battle. And we look forward to being allies with her in that 
effort to see that hope continues.
    Dr. Collins. Senator, that's wonderful, and I will 
personally pass that word of encouragement to her.
    Senator Moran. Thank you.
    Senator Harkin. Thank you, Senator.
    Senator Shelby.

                            VETERAN SUICIDE

    Senator Shelby. I want to follow up on the troubling 
information we have about so many veterans committing suicide 
when they come back from Iraq or Afghanistan, and the 
devastation it does to the families, to the society and so 
forth.
    My question is this, I don't know if you have it, I don't 
know if the VA has it or DOD, but are there statistics, say, 
going back to the end of the Second World War, about the number 
of veterans coming back, the number of suicides per thousand, 
the Korean war, the Vietnam war, the conflict in Iraq and so 
forth. Because that would be very troubling, yes, but maybe 
informative, too, to a point.
    Do you know if they have those statistics, Doctor?
    Dr. Collins. I'm sure there are such statistics. I don't 
have them at my fingertips. And of course, one would have to 
look at the statistics with some caution in the fact that in 
the past, anyway, oftentimes suicides were not reported as 
suicide, because of the stigma attached to that. So, it could 
well be that one looks at those and it looks as if----
    Senator Shelby. That could be skewed.
    Dr. Collins. Yes, they would be skewed, particularly in the 
past and probably still in the present, where suicides, because 
they do carry for families----
    Senator Shelby. Soldiers go through this awful stress in 
combat.
    But as a society, we need to figure out how to prevent it, 
don't we?
    Dr. Collins. I totally agree with you. And again, I think 
if Dr. Tom Insel were on this panel, who is the director of the 
National Institute of Mental Health (NIMH), he would 
immediately put forward to you a number of things that our 
Mental Health Institute is trying to do in terms of identifying 
risk factors and interventions, figuring out how this fits 
together with things like traumatic brain injury and post-
traumatic stress disorder (PTSD).
    Senator Shelby. Thank you very much.
    Thank you, Mr. Chairman.
    Dr. Landis. I think one of the differences between Iraq, 
Afghanistan, or in earlier wars are the improvised explosive 
devices with significant repeated mild traumatic brain injury. 
There's evidence that it's an invisible wound, and soldiers 
often don't recognize that this has been an issue and don't 
seek appropriate help.
    So, I think that the statistics for these wars might be 
different than previous wars.
    Senator Shelby. One added dimension, I just thought of it, 
because so many of our soldiers have had multiple tours--some 
volunteered, some didn't, in all this--which puts a lot of 
stress on them and their families.
    Maybe there are studies into that, too, say one tour, two 
tours, three tours, and dramatic effects.
    Dr. Collins. Yes, I'm quite sure that data has been looked 
at by the Department of Defense and is part of the effort as 
we're identifying risk factors in this STARRS study that ought 
to be looked at very carefully. And if there is some indication 
that the number of tours is a factor, obviously one would want 
to intervene in a prospective way to try to provide that kind 
of support that apparently is not currently sufficient.

                       FUNDING THE FUTURE OF NIH

    Senator Harkin. Thank you, Senator Shelby.
    Well, again I want to thank you all for your dedicated 
public service, your leadership in health.
    It's been my privilege and pleasure to have either chaired 
or been the ranking member of this subcommittee since 1989. So 
I worked with some of you for a long time.
    And every time we have you all up here for NIH, again, it's 
just again a reminder, I think to all of us, that there's just 
certain things we can't back down from. We made so many great 
strides in health research, keeping people healthy, their 
cancer rates. Everything else has been phenomenal, especially 
in childhood leukemia. It's been remarkable.
    And with the Human Genome Project, we now have some keys 
that we've never had before, the new technologies that we have 
that we can use now. It just seems that this is the time to 
redouble our efforts to increase significantly the funding for 
NIH.
    How do you do that? Well, there seems to be an attitude, 
I'm not saying anybody in particular, that we want something 
for nothing. If you want the best, it costs something, in terms 
of the best scientists, the best brains, the best technologies, 
the best equipment. We've always been the best in biomedical 
research in this country.
    I'm afraid that we are falling way behind, so we've got to 
find sources of funding.
    Back in the early 1990s, Senator Mark Hatfield was the 
chair of this committee. And I was ranking member at that time, 
and he was on this subcommittee. This was one of his devotions 
as it is Senator Mikulski's now.
    And we came up with a proposal. I don't know if it was his 
idea or my idea.
    But the basis of it was this, that when you buy a drug, 
when you go out to your pharmacy and you buy a drug today, some 
of that money goes for research. But when you buy a health 
insurance policy, none of that goes for health research.
    So our idea then, and this was about the time, I think, 
when we're working on the Clinton proposed health bill and 
stuff like that, we came up with a proposal, Hatfield and 
Harkin, and that was to have every health insurance policy that 
you would have a certain amount, percentage of each one that 
would then go to the NIH.
    It would come through this committee. And it was only just 
a few cents, a couple, 2 or 3 cents, I think, on the dollar.
    And then someone pointed out, well, but if you do that, 
then that would just supplant what you're doing on the 
discretionary money. So, okay, what we'll do is we'll say, 
okay, it will go into like a trust fund for NIH, but it can 
only be accessed as long as the Congress appropriates at a 
minimum what they did last year, plus an inflation factor.
    Dr. Fauci. That's a good idea.
    Senator Harkin. Well, yes, thank you.
    Well, we tried. We kind of pushed that along for a while. 
We got some pushback, obviously, from the health insurance 
industry, I understand that, and others.
    But then that whole thing sort of faded out and nothing was 
done on it.
    Now with this new healthcare system, Obamacare, coming 
along, there's going to be 35 million more people having health 
insurance policies in this country. Some of them subsidized by 
the Government, others not.
    I just wonder if it's not time. I ask my friends here to 
revisit this and to think about some new source of funding like 
that.
    Yes, the ultimate payer will always be that individual 
person out there, because their health insurance payment will 
go up a little, 2 or 3 cents on the dollar. But they'll have 
the satisfaction of knowing that little increase is going to go 
for only one thing. That's NIH research.
    It can't go anywhere else, and it can only go as long as 
Congress appropriates what we did last year plus an inflation 
factor.
    Somehow, we've got to come up with this funding. Anybody 
else got a better idea, the door is open. I am willing to look 
at anything. If anybody's got a better idea, let me know about 
it.
    Senator Shelby. Mr. Chairman?
    Senator Harkin. Yes.
    Senator Shelby. Did you do some work as to how much money 
that would raise?
    Senator Harkin. Oh, yes. It was quite significant.
    Senator Shelby. It would help a lot?
    Senator Harkin. Oh, big time. And it was just a couple of 
cents on the dollar, was all, when you think about it. And now 
we're going to have a lot more heath insurance policies out 
there.
    And I talked to some of my health insurance carriers, and 
we have a lot of health insurance carriers out there.
    Well, you know, I suppose they could live with it, but it 
wasn't high on their agenda. But again, it's just something I 
think we ought to roll around.
    And like I said, anybody else here in the audience or 
anybody else listening got any better ideas, let me know.
    But we've got to get more funding for NIH. We can't 
continue to go down this road. I got 20 months left here, 19 
months left here. I'd like to see this turned around.

                     ADDITIONAL COMMITTEE QUESTIONS

    Obviously, I'd like to see us start the doubling process 
again, but that won't happen. I understand that. But finding a 
new source of dedicated revenue that will be there and that we 
know will be there year after year after year, that's got to 
happen so that these young researchers, the one you're talking 
about, it's nice to give her a pat on the back and say follow 
your dreams. Yes, I back up what Jerry said on that.
    But there's got to be something there to make sure that 
those dreams are realizable, and that funding has to be there.
    So, yes. Then we need to go on, but I just think this is 
something we've just got to address.
    So the record will remain open for 7 days for additional 
statements or questions for the record.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
             Questions Submitted to Dr. Francis S. Collins
               Questions Submitted by Senator Tom Harkin

    Question. Dr. Collins, last month was the 10th anniversary of the 
completion of the Human Genome Project, which you led and, I'm happy to 
say, came in ahead of schedule and under budget. What have we learned 
from this effort and where are we going?
    Answer. To gain perspective about how the field of genomics has 
advanced since the Human Genome Project (HGP), it is illustrative to 
compare the ``state-of-the-art'' at the beginning of the HGP in 1990, 
at its completion in 2003, and now, in 2013. For instance, during the 
HGP, it took 6-8 years of active sequencing and approximately $1 
billion to generate that first reference sequence of the human genome. 
In 2003, that same feat would have still required 3-4 months and $10-50 
million. But today, a human genome can be sequenced in approximately 1-
2 days for a mere $3-5 thousand. As the time and cost of human genome 
sequencing have plummeted, the power of genomic strategies and the 
volume of generated genomic data have increased profoundly.
    This capacity to generate more data through improved and less 
expensive technologies has enabled researchers to interrogate genome 
structure and function and learn how the genome contributes to health 
and disease. For example, in 1990, we knew of approximately 50 genes 
that, when mutated, caused a human disease; in 2003 that number was 
almost 1,500; and today, it is nearly 3,000. Further, knowledge about 
the genomic bases for our different responses to medications--an area 
of science called pharmacogenomics--also has grown steadily. In 1990, 
only four Food and Drug Administration (FDA)-approved drugs required 
labels that pointed out the relevance of a patient's genomic makeup for 
that medication; by 2003, that number had increased to 46; and today, 
it stands at 106. In fact, genomic contributions to medical research 
have been so substantial that fully half of ``Time'' magazine's ``Top 
10 Medical Breakthroughs in 2012'' reflected genomics accomplishments, 
and these were in large part supported and/or facilitated by National 
Human Genome Research Institute (NHGRI) research programs.
    During the last decade, building on the discoveries of the HGP, we 
have learned much more about how the genome functions and how genomes 
differ from person to person. For instance, in 2012, the ENCyclopedia 
of DNA Elements (ENCODE) project funded by NHGRI published a landmark 
series of papers reporting a catalog of functional elements within the 
human genome. The ENCODE catalog is like a GPS map for the human 
genome--just as by zooming in on a GPS map of the United States (to 
find the location of points of interests like banks and gas stations), 
the ENCODE catalog is now routinely used by researchers worldwide to 
zoom in on regions of interest in the human genome that are important 
for their studies.
    Meanwhile, the 1000 Genomes Project, funded in part by NHGRI, has 
led to a much greater understanding of the variation among human 
genomes. By sequencing the genomes of more than 2600 individuals from 
different populations across the world, the project is identifying 
patterns of variation between individuals and populations that will 
help advance understanding of the genetic factors contributing to many 
common diseases. To date, the 1000 Genomes Project data have been used 
in published research studies focused on autism, Alzheimer's disease, 
cancer, cardiovascular disease, and cirrhosis.
    The field of genomics is now focusing increasingly on the links 
between genomic variation and disease--and how that knowledge can be 
applied clinically. Genomic medicine is being used to advance certain 
medical specialties such as oncology, where genomics-based diagnostic 
methods are increasingly being used for cancer screening and for 
guiding treatment strategies. Examples include the widespread use of 
``BRCA'' testing in patients with familial risk factors for breast and 
ovarian cancer, the use of testing to predict breast cancer recurrence, 
and the use of genomic diagnostic tests to determine the suitability of 
particular therapeutic treatments. Findings being generated through the 
work of The Cancer Genome Atlas--a research program co-funded by NHGRI 
and the National Cancer Institute--are confirming that cancers that 
appear to be morphologically similar can be separated into distinct 
subtypes based on genomic information, thereby informing the choice of 
therapies. Establishing the specific mutations that drive the growth of 
a patient's tumor can prevent the needless and costly use of harsh 
chemotherapeutic drugs that are ineffective for that tumor subtype. 
From less complex diagnostic tests that predict the effect of 
trastuzumab (Herceptin) use in breast cancer, vemurafenib (Zelboraf) 
use in melanoma, or crizotinib (Xalkori) use in lung cancer, to more 
advanced strategies of sequencing a tumor's mutated genome as a means 
to guide treatment, genomic medicine is becoming a powerful tool for 
guiding clinical care.
    Beyond cancer, genomics is also fueling major strides in other 
clinical areas. For instance, National Institutes of Health's (NIH) 
Intramural Undiagnosed Diseases Program applies genomic analyses to 
cases where a diagnosis has proven elusive to medical experts. To date, 
through the program, two new diseases have been discovered, and 50 
patients have received long-sought diagnoses. Similar approaches using 
genome sequencing to diagnose rare diseases have been used in Wisconsin 
(Nic Volker) \1\ and California (Noah and Alexis Beery),\2\ resulting 
in life-altering treatments for the affected patients. Beyond 
applications for disease identification or categorization, a promising 
study at Stanford University showed that DNA sequencing could be used 
to monitor organ transplant recipients non-invasively to detect early 
signs of rejection. Another study, also conducted at Stanford 
University, used genomics to screen a library of existing FDA-approved 
drugs to determine whether they might be repurposed for use in other 
diseases. Through this work, the possibility of repurposing an epilepsy 
drug for use in ulcerative colitis and Crohn's disease, and using an 
anti-ulcer drug to treat certain forms of lung cancer, has been 
highlighted.
    It is worth noting that although the primary aim of the HGP was to 
improve health, the project's effects have not, and will not, be 
confined to the clinic. A report by Battelle Technology Partnership 
Practice (Battelle) published in 2011 showed that the HGP has had a 
very positive impact on the United States economy.\3\ Specifically, the 
report estimates that between 1988 and 2010, Federal investment in 
genomic research generated an economic impact of $796 billion, 
particularly impressive considering that HGP spending between 1990 and 
2003 was only $3.8 billion. The report further found that in 2010, the 
genomic sector directly supported more than 51,000 jobs, indirectly 
supported more than 310,000 jobs, created $20 billion in personal 
income, added $67 billion to the United States economy, generated more 
than $3.7 billion in Federal taxes, and generated more than $2.3 
billion in State and local taxes. An updated report is being published 
by Battelle on June 12th.
---------------------------------------------------------------------------
    \1\ See: http://www.jsonline.com/features/health/111224104.html.
    \2\ Bainbridge MN et al. ``Sci. Trans. Med'', June 15, 2011 Whole-
Genome Sequencing for Optimized Patient Management. http://
www.ncbi.nlm.nih.gov/pubmed/21677200.
    \3\ Tripp, S. ``Economic Impact of the Human Genome Project'' 
(Battelle Technology Partnership Practice: 2011).
---------------------------------------------------------------------------
    Question. Dr. Collins, a Council of Councils working group recently 
recommended that NIH retire all but 50 chimpanzees to a sanctuary, in 
response to an Institute of Medicine report on research involving 
chimpanzees. Are you likely to accept that recommendation? If not, why 
not? Are there any issues or road blocks to moving the chimpanzees?
    Answer. On January 22, 2013, a working group of the Council of 
Councils presented its report to the Council on the Use of Chimpanzees 
in NIH-Supported Research. The report recommended that, among other 
things, ``The majority of NIH-owned chimpanzees should be designated 
for retirement and transferred to the Federal sanctuary system'' and 
that ``A small population of chimpanzees [approximately 50] should be 
maintained for future potential research. . . .'' The same day, the 
Council of Councils accepted these and 26 additional Working Group 
recommendations, and transmitted them to NIH for consideration. NIH 
subsequently issued a request for comments and, after considering the 
public comments, accepted most of the Council recommendations on June 
26, 2013.
    With respect to the recommendation that advises that NIH retire the 
majority of NIH-owned chimpanzees, a vast majority of the commenters 
agreed with this recommendation. However, a number of commenters noted 
that the funding limits of the Chimpanzee Health Improvement 
Maintenance and Protection (CHIMP) Act of 2000 may affect the agency's 
decisions about retiring chimpanzees no longer needed for research. The 
CHIMP Act amended the Public Health Service Act to establish and 
maintain a system of sanctuaries for the lifetime care of chimpanzees 
that were used in research that the Health and Human Services (HHS) 
Secretary (through NIH) designates as no longer needed for research. 
Prior to accepting the Council recommendation, there were already 219 
chimpanzees living in, or were scheduled to be relocated to, the 
Federal sanctuary system. Three-hundred sixty (360) additional NIH-
owned chimpanzees are not retired and reside outside the sanctuary 
system.
    Despite overwhelming public support to retire most NIH-owned 
chimpanzees, three issues need to be addressed before NIH could fully 
implement the recommendation to retire the majority of NIH-owned 
chimpanzees: (1) restrictions on funding levels in the CHIMP Act (often 
referred to as the cap), (2) lack of capacity in the Federal sanctuary 
system, and (3) limits in authority to manage the sanctuary system.

 FUNDING RESTRICTIONS IN THE CHIMPANZEE HEALTH IMPROVEMENT MAINTENANCE 
                           AND PROTECTION ACT

    The CHIMP Act authorized HHS to establish the sanctuary system but 
includes a technical provision that currently limits the amount of its 
financial resources that HHS (through NIH) can provide for: (1) care 
and maintenance of the chimpanzees within the Federal sanctuary system; 
and (2) construction to establish the system. NIH believes that its 
authority to use appropriated monies to fund the Federal sanctuary 
system expires once the funds spent for the operation and establishment 
of the sanctuary system reach $30 million. As of February 2013, NIH had 
spent over $29 million in Federal funding on the sanctuary system and 
expects to reach $30 million early in fiscal year 2014. After that, HHS 
may lack the authority under the CHIMP Act to obligate additional 
funding to the Federal sanctuary system for care and maintenance of the 
chimpanzees within the Federal sanctuary system as well as future 
construction to expand the system. General Provision language has been 
proposed in the fiscal year 2014 President's budget request to remove 
this restriction.

                                CAPACITY

    The agency agrees that the majority of chimpanzees that NIH owns 
could be eligible for retirement but additional capacity in the Federal 
sanctuary system is needed. Although the contractor (Chimp Haven, Inc.) 
that maintains the Federal sanctuary system plans to use private 
funding to construct additional space to house 110 chimpanzees from the 
New Iberia Research Center, these new areas will not be sufficient to 
accommodate the majority of NIH-owned chimpanzees that the Council 
recommended retiring. NIH is currently unable to support construction 
at the sanctuary due to funding restrictions in the CHIMP Act. Without 
additional construction or the authority to support such work 
financially, NIH understands that the Federal sanctuary system will be 
unable to accept additional chimpanzees until the current sanctuary 
population declines.

       LIMITS IN AUTHORITY TO MANAGE THE FEDERAL SANCTUARY SYSTEM

    NIH believes the CHIMP Act also limits the HHS Secretary's 
authority to expand the Federal sanctuary system by adding additional 
compliant retirement facilities. Currently, the system is composed of 
only one sanctuary that is now at capacity, but several facilities have 
approached the agency with an interest in accommodating retired 
chimpanzees. NIH would like to consider additional facilities to add to 
the system so long as they conform to CHIMP Act requirements and the 
implementing of sanctuary regulations.
    To add additional sanctuaries to the Federal system, the CHIMP Act 
requires the HHS Secretary to seek approval from the Board of Directors 
that oversees the nonprofit entity that runs the Federal sanctuary 
system. This provision, consequently, could limit the Secretary's 
ability to retire chimpanzees to other potentially compliant retirement 
facilities that could provide a cost savings or less expensive option. 
HHS believes it should be able to retire chimpanzees directly to other 
facilities if the Secretary determines the criteria in the law are met. 
We would like to point out that it would not incur additional costs to 
retire chimpanzees into an expanded sanctuary system. Funds to support 
their care in the research facilities could be transferred for their 
care in the sanctuary system. Alternatively research facilities could 
be modified to qualify for participation in the Federal sanctuary 
system. Although NIH agrees that the majority of its chimpanzees could 
be designated for retirement and transferred to the Federal sanctuary 
system, NIH is not in a position at this time to implement the 
recommendation.
                                 ______
                                 
            Questions Submitted by Senator Mary L. Landrieu

    Question. A year ago, our Nation adopted a National Plan that set 
as goal one treating and effectively preventing Alzheimer's disease by 
2025. This plan was required under the National Alzheimer's Project 
Act, bipartisan legislation approved unanimously by Congress in 2010. 
Achieving this goal will not be easy. In the past several months, at 
least three industry trials testing potential therapies for Alzheimer's 
have reported disappointing phase 3 study results.
    Based on what you know today, how confident are you that the Nation 
will achieve the 2025 goal of preventing and treating Alzheimer's 
disease?
    Answer. The identification and development of interventions that 
will prevent or treat Alzheimer's disease have proven to be extremely 
challenging, and it is still not possible to predict with certainty 
when an effective treatment or preventive intervention will be 
available. However, we have greater reason than ever before to be 
optimistic.
    Our efforts have been significantly advanced by recent 
breakthroughs in biomedical imaging that are enabling us to identify 
and track the earliest pathological stages of the disease process, long 
before clinical symptoms are apparent. These discoveries, in addition 
to discovery of other early biomarkers of the Alzheimer's disease 
process, have opened a ``window of opportunity'' for us to target and 
potentially reverse the disease's underlying pathology before 
cognitive, behavioral, and emotional symptoms appear. National 
Institutes of Health (NIH) has begun to launch its first such clinical 
trials in presymptomatic individuals. For example, in one high-profile 
study, investigators are studying whether an antibody treatment, 
crenezumab, which is designed to bind to and possibly clear away 
abnormal amounts of amyloid protein in the brains of people with 
Alzheimer's, can prevent decline in cognitive function. Crenezumab is 
being tested among members of a unique and large family population in 
Colombia sharing a genetic mutation known to cause observable signs of 
Alzheimer's disease at around age 45, along with a smaller number of 
U.S. participants ages 30 and older. We anticipate initial results from 
this groundbreaking study by 2017.
    NIH also supports more than 35 Alzheimer's disease clinical trials, 
including a number of studies of interventions to slow disease 
progression among individuals who are already showing symptoms. More 
than 40 compounds are currently under study to stimulate and advance 
research on the discovery and development of new preventive and 
therapeutic interventions for Alzheimer's disease (AD), mild cognitive 
impairment, and age-related cognitive decline.
    Question. What level of funding for Alzheimer's research at the NIH 
do you think is needed to maximize our chances of achieving this goal, 
and what other measures can our Nation take, recognizing these fiscally 
challenging times, to stop this disease?
    Answer. NIH has made one-time internal re-allocations to the 
Alzheimer's disease budget in fiscal year 2012 ($50 million) and fiscal 
year 2013 ($40 million) that have made it possible to develop new 
opportunities in critical priority areas. Sustained availability of 
funds, as indicated in the fiscal year 2014 President's budget request, 
would further facilitate targeted initiatives in high-priority research 
areas. Under the fiscal year 2014 President's budget request, NIH 
currently estimates it would spend a total of $562 million on 
Alzheimer's disease research.
    In the current challenging budget climate, we are continuing to 
take a number of steps to leverage our resources to the maximum extent 
possible. For example:
  --We have developed a rigorous and inclusive process for soliciting 
        expert advice on research priorities, most notably through the 
        May 2012 Alzheimer's Disease Research Summit, at which 
        internationally recognized experts in the field met to 
        formulate an integrated multidisciplinary research agenda that 
        will accelerate the development of successful therapies for AD 
        across the disease continuum. Summit participants also 
        identified the types of resources/infrastructure and new public 
        private partnerships that will be necessary to successfully 
        implement this research agenda.
  --We have created the International Alzheimer's Disease Research 
        Portfolio, a unique database of nationally/internationally 
        funded AD research, which will enable organizations around the 
        world to coordinate funding strategies and leverage resources 
        in order to maximize the impact on public health and avoid 
        duplication of effort and inefficiency.
  --We have conducted an in-depth analysis of the NIH Alzheimer's 
        disease research portfolio and tied specific milestones to the 
        goals of the National Plan to Address Alzheimer's Disease.
  --Where appropriate, we are coordinating efforts with private funders 
        and advocacy organizations and actively pursuing public-private 
        and international partnerships.
    Question. With respect to the level of funding at the NIH for 
Alzheimer's disease, I would like for you to address what appears to be 
an unacceptable gap between the growing costs of this disease to the 
Nation and the amount of our Federal investment. More than 5 million 
Americans are estimated to be suffering from Alzheimer's disease, a 
number that is expected to more than triple by 2050. If the prevalence 
and trajectory of the disease remains unchanged, the total costs 
associated with Alzheimer's disease will near or exceed $1 trillion 
annually by mid-century.
    Answer. In fiscal year 2012, the total NIH expenditure for 
Alzheimer's disease research was approximately $503 million, an 
increase of approximately $55 million, or 12 percent over fiscal year 
2011. This reflected a one-time $50 million increase allocated to NIH 
Alzheimer's research for fiscal year 2012. In fiscal year 2013, NIH is 
also allocating $40 million of funds within the Office of the 
Director's budget to Alzheimer's research. For the fiscal year 2014 
President's budget, NIH estimates it will spend a total of $562 million 
on research related to this disease.
    It is important to recognize that while Alzheimer's research 
continues to be of tremendous importance to NIH, it is one of a number 
of highly compelling priorities that include research on diabetes, 
heart disease, cancer, mental illness, as well as cross-cutting 
research affecting discovery in multiple disease areas. NIH maintains a 
careful, rigorous, and ongoing planning and priority-setting processes 
to ensure an appropriate balance of resources in basic, clinical, and 
translational research, with the ultimate goal of safeguarding the 
health and well-being of all Americans.
    Question. A recent RAND Corporation study published in the New 
England Journal of Medicine estimates that the direct healthcare costs 
associated with Alzheimer's disease are $109 billion annually, 
exceeding the direct care costs associated with cancer and heart 
disease. When costs of informal caregiving are factored in, annual 
costs of Alzheimer's and dementia skyrocket and are estimated today to 
be as high as $215 billion annually. Alzheimer's is the most expensive 
disease to American families and taxpayers--more expensive than HIV 
AIDS, Heart Disease and Cancer. Despite the recognized scope of this 
crisis, NIH is spending approximately $480 Million on Alzheimer's 
research
    How do you explain this disparity between the growing societal 
burden and economic threat posed by Alzheimer's and the very small 
investment we are making at the NIH in Alzheimer's research?
    Answer. In fiscal year 2012, the total NIH expenditure for 
Alzheimer's disease research was approximately $503 million, an 
increase of approximately $55 million over fiscal year 2011. This 
reflected a one-time $50 million increase allocated to NIH Alzheimer's 
research for fiscal year 2012. The National Institute on Aging (NIA) 
funded over $335 million in Alzheimer's disease research--approximately 
one third of the Institute's research budget. For the fiscal year 2014 
President's budget, NIH estimates it will spend a total of $562 million 
on research related to this disease.
    Alzheimer's research continues to be of tremendous importance to 
the NIH and the NIA. The number of individuals with Alzheimer's disease 
continues to increase, and our efforts to identify an intervention that 
will prevent or treat the disease have borne disappointing results. 
However, Alzheimer's disease is one of a number of highly compelling 
NIH priorities that include research on heart disease, cancer, mental 
illness, and diabetes, as well as cross-cutting research that informs 
discovery in multiple disease areas. Both NIH and NIA maintain careful, 
rigorous, and ongoing planning and priority-setting processes to ensure 
an appropriate balance of resources in basic, clinical, and 
translational research, with the ultimate goal of safeguarding the 
health and well-being of all Americans.
    Question.  Do you agree that Alzheimer's research deserves funding 
that begins to approach the scope of the problem it poses? If you agree 
that there is a problem here, please provide specifics on how you 
intend to address this vast disparity in funding within the authorities 
you have available to you today.
    Answer. In this challenging budget climate, we are continuing to 
take a number of steps to leverage our resources to the maximum extent 
possible. For example:
  --We have developed a rigorous and inclusive process for soliciting 
        expert advice on research priorities, most notably through the 
        May 2012 Alzheimer's Disease Research Summit, at which 
        internationally recognized experts in the field met to 
        formulate an integrated multidisciplinary research agenda that 
        will accelerate the development of successful therapies for AD 
        across the disease continuum. Summit participants also 
        identified the types of resources/infrastructure and new public 
        private partnerships that will be necessary to successfully 
        implement this research agenda.
  --We have created the International Alzheimer's Disease Research 
        Portfolio, a unique database of nationally/internationally 
        funded AD research, which will enable organizations around the 
        world to coordinate funding strategies and leverage resources 
        in order to maximize the impact on public health and avoid 
        duplication of effort and inefficiency.
  --We have conducted an in-depth analysis of the NIH Alzheimer's 
        disease research portfolio and tied specific milestones to the 
        goals of the National Plan to Address Alzheimer's Disease.
  --Where appropriate, we are coordinating efforts with private funders 
        and advocacy organizations and actively pursuing public-private 
        and international partnerships.
    Question. I have a longstanding interest in and commitment to 
improving the health of all Americans. The research activities at NIH 
play a critical role in this issue. The National Institute on Minority 
Health and Health Disparities (NIMHD) at NIH only has a budget of 
approximately $200 million, paling in comparison to other NIH 
Institutes and Centers (ICs) like Human Genome Institute with $500 
million or the National Cancer Institute at $5 billion. I stand for 
elimination of health disparities to be a national priority--and for it 
to be funded like one. The NIMHD's budget should be increased to 
fulfill this mission.
    As you know, the RCMI program within the NIMHD is responsible for 
developing and enhancing the research infrastructure of minority 
institutions and directly fosters the development of new generations of 
minority scientists. I am disappointed to see the nearly $6.5 million 
decrease from fiscal year 2012 funds being requested for the Research 
Centers in Minority Institutions program.
    Can you please tell me the rationale in the decreased funding for 
this important program?
    Answer. The Research Centers in Minority Institutions (RCMI) 
program provides resources for several critical areas of support for 
biomedical, clinical, behavioral, and social sciences research. 
Infrastructure development creates a foundation for the research 
enterprise through renovation/alteration of new research facilities and 
the development of specialized research support capabilities such as 
biomedical informatics and research design/biostatistics expertise. 
Activities under the RCMI program broaden the opportunities to conduct 
clinical and translational research through collaborative projects with 
an emphasis on improving minority health and reducing health 
disparities. In addition, instructive training and mentored research 
training experiences for early-stage investigators interested in health 
disparities research facilitate career advancement for junior faculty 
members.
    The RCMI program was transferred to NIMHD in fiscal year 2012 with 
the dissolution of the National Center for Research Resources (NCRR). 
At the NCRR, the RCMI program was one of the Center's main programs 
aimed at addressing minority health and health disparities. Consistent 
with its mission, the NIMHD's program portfolio is exclusively focused 
on improving minority health and eliminating health disparities. 
Integrating the RCMI program into the NIMHD has been a priority for the 
Institute over the past year. This integration means taking a strategic 
look at the Institute's priorities, plans, and the overall portfolio, 
with the goal of balancing our scientific research investments, 
particularly since the RCMI program is programmatically similar to 
other NIMHD congressionally mandated programs. In so doing, the NIMHD 
seeks to ensure that priorities, programs, and resources are 
appropriately aligned consistent with its mission, as well as the 
mission of the NIH; the changing pace of science and the health 
disparities environment; and that duplication in efforts are identified 
and reduced; therefore, a reduction in funding for the RCMI program and 
other NIMHD programs was proposed for fiscal year 2014. NIMHD is 
committed to the goals and objectives of the RCMI program, and to fully 
integrating the program into the Institute in a manner that fosters 
collaboration and partnership between RCMI and other NIMHD/NIH 
programs, and provide opportunities to enhance the program's 
contribution to the Institute's mission, as well as the health and 
well-being of the Nation.
    Question. The National Center for Advancing Translational Sciences 
(NCATS) mission includes a commitment to the behavioral sciences but I 
am concerned that the Center has not taken sufficient action to bring 
basic behavioral and psychological science discovery into new applied 
behavioral interventions. A stronger effort is critical to accelerate 
the translation of basic behavioral research discoveries into broadly 
disseminated new therapeutics and clinical care products and protocols, 
particularly in addressing substance abuse, suicide, depression, and 
similarly urgent public health issues confronting the Nation
    Answer. To bring the benefits of science more quickly into patient 
care, NCATS was formed with the mission to catalyze the generation 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. NCATS' mission includes 
strengthening the entire spectrum of translational research--defined 
broadly to include the early steps necessary to develop new 
therapeutics, devices and diagnostics from basic discoveries, the steps 
necessary to establish real world efficacy, and the research needed to 
improve the practical implementation and dissemination of improved 
approaches to care.
    NCATS is committed to translating basic behavioral and 
psychological discovery into interventions that have a discernible 
impact on human health. These interventions can span the translational 
space of development of a therapeutic, preventive, or diagnostic or 
addressing the critical areas of implementation, dissemination, or 
adherence. New methods and technologies are needed in addressing 
behavioral and psychological interventions as well as greater 
integration of these approaches in all portions of the translational 
spectrum.
    Many Clinical and Translational Science Awards are already 
supporting investigators working in these areas through their study 
design and biostatistical, regulatory, and community engagement 
resources, as well as with pilot project funds for innovative 
approaches. For example, the National Institute on Drug Abuse (NIDA) 
Clinical Trials Network (CTN) provides an enterprise in which NIDA 
treatment researchers, and community-based service providers 
cooperatively develop, validate, refine, and deliver new treatment 
options to patients in Community Treatment Programs (CTPs). The NIDA 
CTN utilizes the resources of the CTSA program at many of its sites for 
their studies of new interventions for substance abuse and addiction.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin

    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.
    The healthcare reform law included a provision, which I authored, 
that authorizes the Centers for Disease Control and Prevention (CDC) to 
expand surveillance and track the epidemiology of CHD across the life-
course, with an emphasis on adults. The Consolidated Appropriations Act 
of 2012 provided the CDC with $2 million in new funding for enhanced 
CHD surveillance.
    Premature deaths across the life-span related to CHD are 
unacceptable, however recent data suggest that the number of infant 
deaths related to CHD is decreasing. Successful interventions in 
infancy and childhood are resulting in an aging population of 
congenital heart disease survivors. How is the National Institutes of 
Health (NIH) systematically responding to this new population of 
survivors reaching adolescence, adulthood, and advanced age? How are 
you utilizing adult congenital heart disease research experts in these 
efforts? How are you supporting adult CHD experts to grow the field? Is 
the NIH offering training grants to grow the field? Is the Pediatric 
Heart Network inclusive to adult CHD experts? Is your agency formally 
engaging adult populations in CHD research?
    Answer. The National Heart, Lung, and Blood Institute (NHLBI) is 
keenly aware of the medical and research needs of adults with 
congenital heart disease and is supporting a number of activities to 
meet these needs.
    The Pediatric Heart Network (PHN) is following a cohort of 
patients, now aged 13-27, who underwent a Fontan procedure, to correct 
a CHD, earlier in life. Assessments include family functioning, quality 
of life, neurodevelopment, and access to healthcare as children 
transition into adulthood.
    The Pediatric Cardiac Genomics Consortium (PCGC), whose goal is to 
understand the genetic basis of congenital heart disease and the 
contributions of genetics to individual patient outcomes, has enrolled 
more than 5000 patients with congenital heart disease, 20 percent of 
whom are adults.
    The Health, Education and Access Research Trial (HEART-ACHD), 
conducted with NHLBI support in partnership with the Adult Congenital 
Heart Association (ACHA) and the Alliance of Adult Research in 
Congenital Cardiology (AARCC), found that more than 40 percent of 
adults with congenital heart disease have a gap in cardiac care of over 
3 years, usually during the critical ``transition'' time from the 
teenage years into the early 20s. The study investigators also found 
that these patients responded well to educational interventions, 
resulting in improved knowledge about their conditions and also about 
research.
    The Research Empowerment for Adult Congenital Hearts (REACH) 
project, another ACHA-AARCC collaboration, received NHLBI American 
Recovery and Reinvestment Act (ARRA) funding to demonstrate the 
feasibility of a patient-centered research model for adults with 
congenital heart disease and employ electronic health record technology 
to create a national infrastructure for research.
    NHLBI has been exploring the use of global unique identifiers 
(GUIDs) to link information already collected in a number of different 
databases on persons with congenital heart disease. PCGC investigators, 
in collaboration with colleagues at the National Institute of Mental 
Health (NIMH) who developed the GUID software, have begun a pilot to 
assign GUIDs to enrolled patients. If successful, GUIDs will be rolled 
out to PHN studies and registries that enroll patients with congenital 
heart disease such as the Society for Thoracic Surgery Registry.
    NHLBI staff responsible for adult and pediatric cardiovascular 
disease research meet regularly with adult congenital heart disease 
experts and ACHA representatives to advise them about NIH research 
opportunities generally, discuss relevant NHLBI activities, and provide 
input into specific research proposals from the community.
    NHLBI supports several research training and career development 
programs that focus on various aspects of congenital heart disease in 
adults, including adherence to treatment and medical outcomes. The 
Institute recently developed a PHN Scholars award to fund small pilot 
studies and encourage young investigators to conduct research in 
congenital heart disease. One of the awards, titled ``The Clinical 
Significance of Abnormal Spirometry after the Fontan Procedure,'' will 
enroll adult participants in the PHN cohort study mentioned above. The 
young investigator's primary mentor directs the Boston Adult Congenital 
Heart Service.
    Question. In May of 2010, the National Cancer Institute (NCI) 
reported that the likelihood of being diagnosed with gastric cancer at 
age 25-39 years had increased by almost 70 percent since 1977. There 
are minimal symptoms of gastric cancer and it is most often diagnosed 
at a late stage when curative treatment is impossible. The American 
Cancer Society (ACS) estimates 21,600 new cases of gastric cancer will 
be diagnosed in 2013 and 10,990 people will die from the disease. 
According to the NCI, about 80 percent of people with stomach cancer 
are diagnosed with advanced metastatic cancer. At stage 4, the 5-year 
survival rate for gastric cancer is four percent.
    Please describe what investments are being made by the NCI to 
improve biomedical discoveries pertaining to gastric cancer. The Cancer 
Genome Atlas (TCGA) provides a rewarding opportunity to enhance our 
understanding of gastric cancer through genomic data. What steps is the 
NCI taking to ensure TCGA data are utilized for gastric research? 
Further, what steps is the NCI taking to assist gastric cancer 
researchers in utilizing the TCGA data to translate promising data from 
the research bench to patient bedsides?
    Answer. Most gastric cancers arise from the gastric epithelium and 
are classified as adenocarcinomas. These are divided into two types, 
the intestinal type, which develops in the antrum and is usually well-
differentiated, and the diffuse type, which develops in the body of the 
stomach, is poorly differentiated, and usually has a poorer prognosis 
than the intestinal type. Gastric cancer does not appear to be 
hereditary in most patients. However, a few with the diffuse type have 
a hereditary form, arising from an inherited mutation in the E cadherin 
gene, which encodes a protein that helps the epithelial cells stick 
together. Most cases of gastric cancer are attributable to infection 
with the bacterium ``Helicobacter pylori (H. pylori)'', and 
progressively stronger evidence suggests that early antibiotic 
treatment of this common infection in high-risk patients can reduce the 
risk of developing this cancer.
    The expected frequency of gastric cancer in 2013 actually 
represents a substantial decrease compared to 80 years ago. Since 1930, 
the incidence and mortality from this cancer have decreased by more 
than 80 percent. The rates continued to decline during the first decade 
of the 21st century, according to the 2013 Annual Report to the Nation 
on the status of cancer, a joint effort of the American Cancer Society, 
the Centers for Disease Control and Prevention, and the NCI. The report 
also notes that during this decade, the incidence of gastric cancer 
decreased about 15 percent for men (who account for about 60percent of 
cases) and a little under 10 percent for women, while its mortality 
rate decreased even faster, by more than 30 percent for men and more 
than 25 percent for women. Nevertheless, gastric cancer remains a 
formidable disease, with most advanced cases having a poor prognosis. 
The NCI has more than 80 research projects devoted at least in part to 
gastric cancer. Several other NIH Institutes, especially the National 
Institute of Allergy and Infectious Disease (NIAID) and the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), also 
support research in this area, with emphasis on ``H. pylori''.
    Gastric cancer is one of the cancers being studied by The Cancer 
Genome Atlas (TCGA), which is a joint research effort of the NCI and 
the National Human Genome Research Institute. TCGA is expected to have 
a major impact on our understanding of the genetic and epigenetic 
changes associated with more than 30 cancer types being studied in 
unprecedented detail in this initiative. Tumor tissues from 
approximately 325 cases have been collected to date and are being 
analyzed. Data is expected to be available next year.
    In general, TCGA data is being used to refine the diagnosis of 
cancer, to define and delineate both the heterogeneity and the common 
features of various cancer types, and to elucidate the molecular 
pathways that control the malignant behavior of cancer cells, with the 
long-term goal of improving the outlook for cancer patients. These data 
are available to qualified researchers through public databases 
designed to protect patient privacy. The TCGA team provides extensive 
support to researchers accessing TCGA data, including step-by-step 
protocols for how to apply and locate TCGA data, as well as preliminary 
data analysis to those not able to manipulate the raw data. The 
availability and broad utilization of the TCGA data are demonstrated by 
the number of publications using TCGA data (to date, already close to 
400) and the number of grant applications that include TCGA data (to 
date, more than 800). TCGA works with investigators and other 
components of NCI to help apply findings from TCGA to the development 
of new diagnostics and therapeutics.
    The era of targeted treatment of gastric cancer, with research 
support from the NCI, has begun even before the TCGA data on this 
cancer become available. One recurring therapeutically relevant theme 
in cancer is that abnormalities in one tumor type may also be found in 
other tumor types. In this context, the protein encoded by the ErbB2 
gene, which was found initially to be effectively targeted in breast 
cancer by a specific monoclonal antibody, trastuzumab, has also been 
found to be overexpressed in some gastric cancers; treatment of these 
patients with trastuzumab, in conjunction with standard chemotherapy, 
can increase their overall survival, which has led to its approval by 
the FDA for the treatment of gastric cancer. Encouraging preliminary 
results in gastric cancer have also been seen with therapy directed 
against other molecular targets, such as epidermal growth factor 
receptor (EGFR) and vascular endothelial growth factor (VEGF).
    Prevention is another important NCI-supported area. Research on 
``H. pylori'' has provided insight into the observed differences in 
oncogenicity among different strains of the bacterium. These basic 
research findings have clinical implications, as they can identify 
those patients most likely to benefit from eradication of their ``H. 
pylori'' with antibiotics.
    We anticipate that the detailed information from TCGA and other 
research from NCI-sponsored grants will bring new information about the 
causes of gastric cancer and its pathogenesis, and will identify new 
molecular targets, leading to continued progress in our efforts to 
fight this cancer.
    Question. In fiscal year 2013 alone, sequestration threatens to cut 
the NIH's $30.7 billion budget by almost $1.6 billion. This reduction 
in funding jeopardizes NIH's ability to invest in biomedical research 
and slows the pace of discoveries. Please summarize the impact of 
sequestration on NIH's ability to award grants and support the training 
and education of scientists. Please describe the impact of 
sequestration on biomedical innovation and how the cuts in funding may 
impact patients currently enrolled in clinical trials. Are you aware of 
reports quantifying the ripple effect sequestration has on biomedical 
research, biotechnology industries, and economic development in the 
United States?
    Answer. Sequestration requires NIH to cut 5 percent or $1.55 
billion of its fiscal year 2013 budget. NIH must apply the cut evenly 
across all programs, projects, and activities (PPAs), which are 
primarily NIH institutes and centers. This means every area of medical 
research will be affected. Compared to fiscal year 2012, NIH expects to 
issue approximately 700 fewer competitive research project grants and 
admit approximately 750 fewer new patients to the NIH Clinical Center. 
In addition, NIH will not increase training stipends for National 
Research Service Award recipients in fiscal year 2013. While much of 
these decreases are due to sequester, NIH funding is always a dynamic 
situation with multiple drivers.
    The reductions imposed under sequestration have, and will continue 
to have a negative impact on biomedical innovation and the training and 
education of young scientists. Medical breakthroughs do not happen 
overnight. In almost all instances, breakthrough discoveries result 
from years of incremental research to understand how disease starts and 
progresses. Even after the cause and potential drug target of a disease 
is discovered, it takes on average 13 years and $1 billion to develop a 
treatment for that target. NIH is aware that its research funding 
directly supports hundreds of thousands of American jobs and serves as 
a foundation for the medical innovation sector, which employs 1 million 
U.S. citizens. Cuts to NIH funding will have an economic impact in 
communities throughout the U.S.
    For additional details on the impact of sequestration see: http://
www.nih.gov/news/health/jun2013/nih-03.htm
                                 ______
                                 
                Questions Submitted by Senator Jack Reed

    Question. The Congressional Budget Justification for the National 
Institute of Child Health and Human Development highlights the National 
Children's Study as an ``unprecedented opportunity'' to examine factors 
that affect child health and development. However, the research 
community continues to raise concerns with the major changes to the 
design of this landmark study proposed by the National Institutes of 
Health (NIH).
    The NIH is supposed to have a contract in place with the IOM to 
review the Vanguard Study and new proposals by the end of May. Has that 
contract been signed?
    Answer. The fully executed Task Order for the contract with the 
Institute of Medicine (IOM) to review the study design for the National 
Children's Study (NCS) Main Study was signed on May 28, 2013. The 
period of performance for the contract began June 3, 2013.
    Question. What process are you developing in anticipation of the 
final report next year in order to incorporate the recommendations from 
the IOM into the methodology for carrying out the Main Study?
    Answer. All procurements related to data collection for the Main 
Study are delayed until after the IOM report is released. The content 
of those solicitations will be based on the recommendations of the IOM 
panel, and guided by ongoing public discussions with the NCS Federal 
Advisory Committee, the Independent Study Monitoring and Oversight 
Committee, and the Federal Consortium. These groups will meet within 
the month following the projected public posting of the IOM report in 
June 2014. The NIH will integrate the IOM recommendations with input 
from the advisory committees to construct the NCS Main Study, including 
the Study's methodologies and implementation plan. New solicitations 
based on the updated design, methodologies, and implementation plan 
will be published at least 60 days following the release of the IOM 
report.
    Question. Presuming the data already collected could be useful, 
will researchers have access to the data already collected while the 
IOM conducts its study? Could NIH provide grants through other programs 
to use the data that the Federal government already spent $1 billion to 
collect?
    Answer. Qualified researchers, whether or not they are directly 
associated with the NCS, already have access to the Study data, and 
will throughout the course of the Study. While we anticipate that many 
NIH Institutes and Centers may choose to support grants that utilize 
NCS data and samples, access to NCS data and samples will not require 
such grants.
    Question. I understand that NIH is currently engaged in an internal 
process to evaluate how it tracks research data on age, gender, race, 
and other patient identifiers. What is the timeline for completing this 
process?
    Answer. In 2010, the NIH Principal Deputy Director convened an 
internal task force to evaluate the policies and procedures related to 
the inclusion of women, minorities, and children. Among the outcomes of 
the task force was the formation of a new Subcommittee on Inclusion 
Governance (SIG) in November 2011, co-chaired by Dr. Janine Austin 
Clayton, Associate Director for Women's Health, and Dr. Alan 
Guttmacher, Director, ``Eunice Kennedy Shriver'' National Institute of 
Child Health and Human Development.
    With input from the task force, the SIG is taking a comprehensive 
look at the NIH policies regarding the inclusion of women, minorities, 
children, and other population groups in clinical research and clinical 
trials. The SIG has reaffirmed that the primary goal of NIH inclusion 
policies is not enumeration, but rather to ensure that the distribution 
of participants in clinical research reflects the population(s) needed 
to accomplish the scientific goals of the study. Investigators, 
reviewers, and NIH staff all have key roles to play in implementing and 
monitoring the policies.
    Data collection on the basis of sex/gender, race, and ethnicity is 
currently being re-engineered to streamline and simplify the processes 
and align better with the electronic grant application procedure. We 
anticipate the new system will be deployed in mid-late 2014. With 
respect to age, the governance committee is examining how information 
about age is provided by grant applicants, reviewed during the peer 
review process, monitored during the period that the study is carried 
out, and captured by internal NIH systems. In addition, the 
subcommittee is analyzing the NIH pediatric portfolio to determine 
what, if any, modifications may be needed to ensure the inclusion of 
women, minorities, and children in NIH clinical research.
    Question. The National Institute of Child Health and Human 
Development (NICHD) conducts the majority of pediatric research among 
all of the Institutes, but a substantial portion of the research 
relevant to children occurs in the Institutes across NIH. For research 
projects that are not designed specifically for children--but could 
possibly be relevant to children--how does NIH work with investigators 
to determine the appropriate participation of children?
    Answer. While the NICHD does support a plurality of the pediatric 
research funded by the NIH, nearly every NIH Institute and Center (IC) 
reports annual support for pediatric research. This support comprises 
new and continuing investigator-initiated pediatric research projects, 
and projects funded under Funding Opportunity Announcements. These 
projects are coded using NIH's Research, Condition, and Disease 
Categorization process, a computerized tool that allows the NIH to 
provide consistent and transparent information to the public, providing 
a list for each fiscal year of all NIH-funded projects related to a 
specific research category: 
http://report.nih.gov/rcdc/. If a given project is sufficiently related 
to an area of pediatric research, it will be included in the Pediatric 
Research category.
    NIH also supports a range of mechanisms to foster pediatric 
research training and career development, and an active pediatric 
research loan repayment program, which enables qualified health 
professionals who commit to conducting pediatric research for at least 
2 years to receive a substantial repayment of their educational loans. 
These programs signal to the research community the importance of 
pediatric research and the commitment of the NIH to fostering this area 
of science.
    On a more individual basis, the NIH peer review process helps 
researchers to refine and clarify the goals of their research 
applications or proposals. Reviewers can be helpful in providing 
guidance to applicants who wish to conduct clinical research, including 
whether their proposed research includes adequate numbers of 
individuals from affected populations. Researchers whose projects 
receive funding then work with NIH program officials during the entire 
course of the grant or contract, reporting on their progress annually 
and receiving input from those officials about whether their aims are 
being successfully met.
    Question. What more could NIH be doing to support investigators in 
pediatric enrollment in their research studies and clinical trials?
    Answer. NIH is committed to ensuring that children participate in 
the full range of NIH research. In fiscal year 2012, NIH pediatric 
research funding totaled approximately $3.6 billion, including studies 
in pediatric patients conducted in NIH's intramural research program at 
the Clinical Center in Bethesda, MD. NIH supports nearly 100 
multidisciplinary center and network programs focused on children's 
health needs. These include the Autism Centers of Excellence, the Paul 
D. Wellstone Muscular Dystrophy Cooperative Research Centers, and the 
Children's Oncology Group. NIH's Office of Rare Diseases Research and 
several NIH Institutes and Centers fund the Rare Diseases Clinical 
Research Network to facilitate collaboration among experts in many 
different types of rare diseases. NIH works with the FDA to administer 
the Best Pharmaceuticals for Children Act to support and coordinate 
pediatric pharmacology research, with the goal of increasing the dosage 
and efficacy information available about therapeutics used by children. 
The 60 centers that comprise NIH's Clinical and Translational Sciences 
Awards include substantial pediatric expertise.
    NIH reviews and awards these and other networks and centers 
programs on a regular basis, usually at about 5-year intervals, 
ensuring that they are productive and continue to produce the best 
science. For example, during the coming year, the NIH will post a 
funding opportunity announcement seeking applications for sites to 
participate in the ongoing Collaborative Pediatric Critical Care 
Research Network, which provides the infrastructure to pursue rigorous 
clinical trials and other studies in pediatric critical care medicine. 
The eight currently funded sites include pediatric expertise in 
pulmonology, cardiology, nursing, and other disciplines essential to 
children's health.
                                 ______
                                 
               Questions Submitted by Senator Jon Tester

    Question. Most of the research programs that receive NIH research 
grants are affiliated with an institution of higher education. I 
encourage you to support non-University and non-hospital affiliated 
research institutions throughout the country, and in particular to 
focus on those located in rural America. Academic and non-profit 
institutions based in rural States consistently receive less funding 
from the NIH. This oversight is compounded when their work is 
overlooked by other researchers, regardless of the quality of their 
science.
    Due to a lack of higher education or medical facility affiliation, 
outstanding research institutions in rural areas often struggle to 
obtain research support and funding. I am concerned that the bias 
towards researchers with affiliations is short-sighted and overlooks 
quality research being done by nimble, independent institutes.
    In 2012, the NIH received 63,524 research grant applications. How 
many of those grant applications were from facilities and researchers 
not affiliated with an institution of higher education? How many of the 
grants ultimately awarded went to independent small research 
institutions?
    Answer. In fiscal year 2012, more than 18,500 applications were 
submitted by organizations that were not institutions of higher 
learning. Approximately 4,600 of these applications were submitted by 
nonprofit independent research organizations, and approximately 800 of 
the applications submitted by nonprofit independent research 
organizations were awarded grants. Independent research organizations 
have a success rate that is comparable to those of research hospitals 
and institutions of higher learning.
    Question. How do the sequestration cuts further impact the ability 
of small research institutions' access to grants? What steps is the NIH 
taking to mitigate this issue and ensure that smaller institutions can 
compete with larger institutions?
    Answer. NIH's post-sequestration fiscal policy applies similar 
reductions in funding to all organizations regardless of institution 
size or type. Investigators from all types of organizations, including 
small academic institutions and research organizations, often develop 
collaborations with research personnel at large institutions to gain 
access to resources that would not otherwise be available to them. NIH 
encourages these collaborations and works to ensure access to research 
resources and technologies among its grantees through its sharing 
policies (http://grants.nih.gov/grants/sharing.htm)
    In addition, the Academic Research Enhancement Award (AREA) grant 
program supports small-scale research projects in the biomedical and 
behavioral sciences conducted by faculty and students at educational 
institutions that have not been major recipients of NIH research grant 
funds. Eligible institutions are institutions of higher education that 
do not receive more than $6 million per year in NIH support in each of 
four of the last 7 years. NIH remains committed to the AREA grant 
program in the face of budget restrictions.
                                 ______
                                 
             Questions Submitted by Senator Jeanne Shaheen

    Question. Diabetes and its complications significantly impacts our 
Nation's health and economy. In fact, new estimates show that the 
disease costs our Nation $245 billion annually, a 41-percent increase 
from 2007. It is the number one cause of end-stage renal disease 
(ESRD), which is the largest driver of Medicare costs at $29 billion in 
Medicare in 2009.
    I understand that tight blood sugar control can cut in half the 
incidence of ESRD and could save Medicare over $126 billion in 25 
years. Given this personal and economic toll on our Nation, how is 
National Institutes of Health (NIH) prioritizing diabetic kidney 
disease? What, if any, are some new insights into the prevention and 
treatment in the area of kidney disease?
    Answer. There is no known way to restore kidney function once it is 
lost, but treatment can usually slow or prevent degradation of kidney 
function if diabetic kidney disease is detected early. Therefore, 
prevention and early detection of kidney disease are important research 
priorities. At the NIH, the Institute with the primary responsibility 
for supporting research related to diabetes and kidney disease is the 
National Institute of Diabetes and Digestive and Kidney Diseases 
(NIDDK), and many of the research efforts included below have been 
supported by this Institute.
    The NIDDK's Diabetes Control and Complications Trial showed that 
intensive blood glucose control reduces risk of complications of the 
kidneys, eyes, and nerves of people with relatively recent onset type 1 
diabetes; the U.K. Prospective Diabetes Trial established that careful 
blood glucose control provides similar benefit to people with recent 
onset type 2 diabetes. The NIDDK's Diabetes Prevention Program clinical 
trial moved that prevention effort one step earlier, even before the 
onset of diabetes. It found that people at risk of developing type 2 
diabetes can prevent or delay disease onset and improve their blood 
sugar through an intensive diet and exercise intervention, or, to a 
lesser degree, with the diabetes drug metformin. In cases where people 
receiving the lifestyle intervention actually progressed to develop 
type 2 diabetes anyway, their diabetes was found to be easier to 
control, and to confer a lower risk for complications.
    Despite these efforts to proactively and aggressively manage 
diabetes, the risk for end-stage renal disease (ESRD) in patients with 
chronic kidney disease (CKD) associated with diabetes remains high. 
Moreover, among the larger population of people with CKD who have not 
progressed to ESRD, cardiovascular disease poses a significant burden. 
The NIDDK's Chronic Renal Insufficiency Cohort (CRIC) Study, which 
started in 2001, is a prospective observational cohort study of 
approximately 4,000 men and women and is the largest cohort study of 
CKD yet undertaken. The objectives of the Chronic Renal Insufficiency 
Cohort (CRIC) Study are to improve understanding of the relationship 
between CKD disease and cardiovascular disease and to examine 
traditional and non-traditional risk factors for progression of these 
diseases. An emphasis was placed on recruiting participants at high 
risk for ESRD, including persons with diabetes (about one-half of the 
study participants), African Americans (also about one-half of the 
study participants) and Hispanic Americans. Important scientific 
findings are emerging from this study. For example, fibroblast growth 
factor 23 (FGF-23) is a growth factor that regulates phosphate 
metabolism. Elevated FGF-23 was shown to be an independent predictor of 
risk for ESRD in patients with relatively well-preserved kidney 
function. FGF-23 may turn out to be a useful biomarker to predict risk 
of adverse outcomes in patients with CKD. In a separate study, 
increased levels of FGF-23 were associated with an indicator of 
cardiovascular disease. CRIC Study investigators have also found a 
strong association between eye disease and levels of kidney function, 
suggesting that eye disease may reflect underlying CKD. In addition, 
the increased burden of cardiovascular disease in Hispanic Americans 
with CKD has been documented. These and other findings from the CRIC 
Study in the coming years are expected to inform clinical trials and 
clinical management practices to reduce the burden of ESRD in the U.S.
    The NIH is also seeking to improve the translation and 
implementation of treatment approaches to kidney disease and diabetes 
in a real-world setting. This research seeks to identify factors that 
lead to the adoption, maintenance, and sustainability of science-based 
interventions at the practice level, where they can have an immediate 
impact on patients' lives, such as improving blood pressure control, 
improving laboratory measures of metabolic control or nutritional 
status, and/or changes in kidney function. Looking forward, the NIH 
recently asked the community to identify research objectives that would 
improve our understanding of basic kidney function and aid in the 
prevention and treatment of impaired kidney function and prevention of 
progression to ESRD, welcoming interested parties to submit, discuss, 
and prioritize ideas via an interactive Web site. The approaches 
identified may aid in the discovery of new therapies, the 
identification of regulatory pathways, the generation of animal models 
for preclinical work, and the development biomarkers with clinical 
utility so that diabetic kidney disease patient outcomes can be 
improved.
    Question. Over the past few years, I have been concerned that the 
level of funding for NIDDK in the President's budget proposals has not 
kept pace with the rate of biomedical inflation and the growing 
diabetes epidemic, threatening the ability of NIDDK to continue to make 
progress on promising diabetes research.
    Would you please share the percentage of grants that NIDDK has been 
able to fund over the past 2 years and how this will affect grants/
research going forward?
    Answer. In fiscal year 2011 and fiscal year 2012, the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) used 81 
and 80 percent of its regular appropriations, respectively, to fund new 
and continuing grants supporting the biomedical research enterprise at 
sites around the country. This support includes research project 
grants, research centers, careers, other types of research support, and 
research training awards for individuals and institutions. In those two 
fiscal years, the NIDDK sustained a success rate for funding research 
project grants--which receive the majority share of grant funding--of 
21 and 20 percent, respectively. These data reflect a combined success 
rate for funding research project grants supported by the NIDDK's 
regular appropriation and the Special Statutory Funding Program for 
Type 1 Diabetes Research. The success rate is defined as the percentage 
of reviewed grant applications that receive funding, and is calculated 
for the fiscal year. In fiscal year 2013, we expect that the success 
rate will decline somewhat due to the loss of funds through 
sequestration. At the President's budget request level for fiscal year 
2014, the NIDDK anticipates a success rate for funding research project 
grants of 22 percent. These relatively stable success rates for 
research funding are enabling NIDDK to continue to foster progress and 
new advances in diabetes.
    Question. Would you also please share how the Administration plans 
to ensure that there is a strong investment in the NIDDK in fiscal year 
2014 that will lead to breakthrough discoveries and ultimately a cure 
of diabetes?
    Answer. The President's fiscal year 2014 budget request reflects a 
strong commitment of the NIDDK to support research tackling diabetes 
and its devastating health and economic consequences. For example, the 
funds requested for fiscal year 2014 will enable the NIDDK to continue 
major diabetes clinical trials, such as a recently launched multicenter 
study of the comparative effectiveness of four common drugs used for 
treating type 2 diabetes, and a new trial testing vitamin D for type 2 
diabetes prevention. The fiscal year 2014 budget request will also 
enable NIDDK to pursue emerging opportunities in the study of diabetes 
risk genes in minority populations, which could lead to new therapeutic 
approaches. These resources will also support NIDDK's plans for 
research that can lead us to personalized medicine for diabetes--for 
example, the Institute plans to support research to elucidate how an 
individual's genetic makeup affects his or her response to anti-
diabetic medications, such as metformin. Under the President's budget 
request, the NIDDK will continue to fund translational research in 
fiscal year 2014 and support health information dissemination 
activities to bring scientific discoveries in diabetes to real-world 
medical practice and other community settings. NIDDK plans for fiscal 
year 2014 also include advancing research on brown fat--an exciting new 
area of study with therapeutic potential--and moving forward with major 
studies of gestational diabetes. Moreover, the NIDDK investment in 
diabetes research is augmented by the research activities of the many 
NIH Institutes, Centers, and Offices with an interest in diabetes and 
its complications, which will also continue in fiscal year 2014. All 
these efforts will be further enhanced by fiscal year 2014 mandatory 
funds from the Special Statutory Funding Program for Type 1 Diabetes 
Research, and the NIDDK will convene an expert panel on June 6-7, 2013, 
to obtain external scientific and lay input on future research 
directions to be pursued with these funds.
    Our plans for fiscal year 2014 are contingent upon Congressional 
action, but we are hopeful that the fiscal year 2014 investment in 
diabetes research, spearheaded by NIDDK, will continue to lead us 
toward new discoveries, new therapies, and possibly cures for diabetes.
                                 ______
                                 
               Questions Submitted by Senator Jerry Moran

    Question. As a follow-up to my questions at the hearing on the 
Brain Research through Advancing Innovative Neurotechnologies (BRAIN) 
Initiative, I understand that the National Institutes of Health (NIH) 
is currently working on a scientific plan for this program. However, I 
remain concerned that we have no details on how much funding would need 
to be provided in the coming years. Could you please provide the 
subcommittee a 10-year budget estimation, both for the overall mapping 
project and NIH's share in particular.
    Answer. It will be imperative that cost estimates be strongly 
informed by a rigorous scientific planning process. NIH has charged a 
high-level advisory group with developing a plan for the NIH BRAIN 
Initiative, which is to include timetables, milestones, and cost 
estimates. As part of this process, members will consult the scientific 
community, patient advocates, and the general public to ensure that 
this plan is informed by stakeholder input. Interim recommendations are 
expected late this summer and final recommendations are anticipated in 
the summer of 2014. This plan will be publicly available and widely 
shared with both the public and with BRAIN Initiative partners.
    Question. As the lead institution, do you foresee NIH's funding 
role being increased in future years?
    Answer. It is anticipated that as the BRAIN Initiative gains 
momentum, additional funds may be needed to support promising areas of 
research. The pace at which NIH's role might grow in future years will 
depend on the relative competing priorities and the overall 
availability of funds at that time.
    Question. Will NIH be expected to be the primary funding agency in 
future years?
    Answer. At this time, each funding agency is undertaking an 
extensive scientific planning process to identify their specific areas 
of focus and to define their potential investments in the BRAIN 
Initiative. Given that NIH has such a substantial investment in 
neuroscience research, it is certain that we will remain a leader in 
advancing the goals of the BRAIN Initiative.
    Question. Can you specify the role you see each Federal agency 
taking in this initiative?
    Answer. In general, NIH will develop new tools, training 
opportunities, and other resources. The Defense Advanced Research 
Projects Agency (DARPA) intends to explore applications--such as a new 
generation of information processing systems and restoration 
mechanisms--that dramatically improve the way we diagnose and treat 
soldiers suffering from post-traumatic stress, brain injury, and memory 
loss. The National Science Foundation (NSF) has expressed a commitment 
to supporting research that spans physical, biological, social, and 
behavioral sciences. Moving forward the agencies will work in close 
collaboration to ensure that their efforts are complementary and 
leverage the unique missions of each; ultimately catalyzing an 
interdisciplinary effort of unprecedented scope.
    Question. What role do you expect private research institutions to 
play in the project?
    Answer. Currently there are four private partners involved in the 
BRAIN Initiative: the Allen Institute for Brain Science, the Howard 
Hughes Medical Institute, the Salk Institute for Biological Studies, 
and the Kavli Foundation. Each partner will support areas of research 
in which they are best positioned to advance the overarching goals of 
the BRAIN Initiative. The Allen Institute for Brain Science, a 
nonprofit biomedical research organization, is a leader in large-scale 
data generation, for example, mapping gene expression in mouse, monkey 
and human brains and public sharing of data and tools. The Howard 
Hughes Medical Institute, the Nation's largest nongovernmental funder 
of basic biomedical research, has a focused investment in developing 
and disseminating new imaging technologies for use in model organisms. 
The Kavli Foundation will encourage the application of nanotechnology 
to neuroscience.
    Question. Is it your goal to expand the public-private partnership 
for this initiative in the future?
    Answer. NIH's first goal is to develop a rigorous scientific plan 
for the BRAIN Initiative that is sufficiently informed by a broad and 
inclusive process. After the scientific plan is established, NIH will 
continue to seek ways to leverage public-private partnerships.
    Question. What would happen if each of the proposed agencies does 
not provide the requested amount in fiscal year 2014?
    Answer. The NIH Director recognizes the tremendous opportunity of 
the BRAIN Initiative and is committed to ensuring its success. In the 
event that funds are not provided for this Initiative, NIH will 
continue to support smaller aspects of this project that continue to 
advance neuroscience research. However, the scale of this project might 
be minimized in comparison to the President's bold vision of truly 
``revolutionizing'' our understanding of the human brain.
    Question. The goal of the Institutional Development Award (IDeA) is 
to broaden the geographic distribution of NIH funding for biomedical 
and behavioral research. This is the second year in a row that NIH has 
proposed reducing funding for the IDeA program after Congress restored 
funding in the prior year. I question why the budget would reduce 
funding for the IDeA program whose purpose is to diversify biomedical 
research to all regions of the country when the budget requests new 
funding for new proposals to diversify the biomedical workforce. Why is 
NIH not supporting level funding for the IDeA program which is already 
a critical component of diversifying the biomedical research capacity?
    Answer. At a time of difficult economic environment when many 
investigators throughout the Nation are struggling to compete for NIH 
funding, the allocation of funding for selected States to increase 
their competitiveness must be balanced with other NIH initiatives for 
promoting a more diverse biomedical workforce nationwide.
    Question. The IDeA program is operating under a budget of $262.5 
million for the remainder of fiscal year 2013. Dr. Collins, if your 
budget request of $226 million were agreed to, the IDeA program would 
issue no new Centers of Biomedical Research Excellence (COBRE) awards 
in fiscal year 2014 and cut the COBRE grants currently funded. Why 
would you propose funding reductions that require reducing existing 
awards to a current program whose goal is to increase diversity, while 
then proposing a new diversity initiative within the Common Fund?
    Answer. The IDeA Program is a funding set-aside designed to build 
research capacity in selected States to the point where investigators 
in these States can compete for NIH funding. We have proposed returning 
the IDeA program appropriation to the level where it had been before 
the one-time spike in fiscal year 2012. The IDeA program is a 
congressionally mandated program envisioned as a long-term initiative 
for building biomedical research competitiveness of selected States 
while the Common Fund initiative is a limited term program designed to 
support student development from underrepresented groups.
    Question. Given today's Federal budget constraints and drug 
companies' hesitation to pursue costly development of drugs that may 
have a low success rate, I believe programs like NCATS' Learning 
Collaborative is an innovative model to help address these issues. As 
we discussed in this hearing last year, the University of Kansas Cancer 
Center has engaged in a partnership with the National Center for 
Advancing Translational Sciences (NCATS) and the Leukemia & Lymphoma 
Society to repurpose auranofin, an arthritis drug, for use on a rare 
form of blood cancer. The Learning Collaborative has repurposed a drug 
from the shelf into a clinical trial in less than 2 years, and at one-
sixth the cost of developing a new drug. Dr. Collins, could you talk 
about the progress the Learning Collaborative has made?
    The success of this project appears clear--within 2 years, The 
Learning Collaborative has moved a compound to treat arthritis into a 
Phase IIa Clinical Trial to treat Chronic Lymphocytic Leukemia (CLL), a 
rare blood cancer. This project has not only shown promising results 
for those suffering from CLL, but the research studying auranofin has 
also helped broaden our understanding of how the drug may work to fight 
other forms of cancer. As a result of this initiative, the University 
of Kansas was able to submit two additional investigational new drug 
applications to study auranofin's effects on other forms of cancer. Dr. 
Collins, do you expect this model to be replicated with other 
repurposing initiatives?
    Answer. Parallel, independent studies conducted at The University 
of Kansas (KU) and University of Rochester demonstrated positive 
results when using auranofin to treat a rare, difficult to treat 
lymphoma called Mantle Cell Lymphoma. Investigators at both NCI cancer 
centers believe that auranofin acts synergistically with a class of 
anticancer agents called proteosome inhibitors (e.g., Velcade or 
bortezomib) to treat this cancer. Velcade is not very effective when 
given alone to treat this lymphoma. In a series of collaborative 
experiments with University of Kansas, NCATS obtained results 
supporting the use of Velcade with auranofin to treat this cancer. As a 
result, on March 15, 2013, KU investigators filed a second 
Investigational New Drug (IND) application with the Food and Drug 
Administration (FDA). In late April, FDA cleared researchers to proceed 
with a clinical proof-of-concept trial, studying auranofin alone and in 
combination with Velcade, in lymphoma patients. This trial will be 
conducted at the University of Rochester, University of Iowa, and 
University of Kansas NCI cancer centers.
    Investigators at KU submitted a third IND on March 28, 2013, 
seeking clearance to study auranofin for the treatment of 
gastrointestinal stromal tumors (GIST). The cancer, GIST, afflicts 
approximately 4,000 U.S. patients. Auranofin is active, in the test 
tube, in treating GIST that is both sensitive and resistant to Gleevec. 
Very recently, investigators received clearance from the Food and Drug 
Administration (FDA) to proceed with this trial. The trial will be 
conducted at the University of Kansas Cancer Center and Children's 
Mercy Hospital in Kansas City, MO.
    Auranofin was discovered as active against these cancer cells in 
screens of the NCATS Pharmaceutical Collection (NPC), a comprehensive 
collection and database of approved and investigational drugs. NCATS 
collaborates with investigators worldwide to identify other drugs in 
the NPC that can be repurposed for unmet medical needs.
    Question. How will NCATS share the lessons learned in these types 
of collaborations so others in the field of translational research can 
benefit?
    Answer. Sharing the lessons learned is the best way for NCATS to 
increase the impact of its programs. When the Center develops a 
strategy and demonstrates the value of that strategy, the dissemination 
and adoption of the strategy by other organizations in both the public 
and private sectors is how NCATS will amplify the impact of its 
investment. Such dissemination is accomplished via sharing of data and 
template agreements in public Web sites, peer-reviewed publications, 
and presentations to stakeholders. NCATS uses all of these strategies 
to disseminate lessons learned and communicate the value of our 
strategies. For example, NCATS collaborated with FasterCures, a center 
of the Milken Institute, to disseminate the collaborative lessons from 
The Learning Collaborative with KU and the Leukemia & Lymphoma Society 
(LLS) via webinars, and made the Research Collaboration
Agreement (http://train.fastercures.org/pdf/tools/
CollaborationAgreementNCATS
012412.pdf) and Memorandum of Understanding (http://
train.fastercures.org/pdf/tools/RedactedMOU5June2012.pdf) public for 
others to use.
    Question. Through Federal investment, the NIH has advanced our 
understanding of health for the last century. But the NIH provides more 
than medical discoveries, it creates and sustains jobs and produces 
measurable benefits to the American economy. Dr. Collins, at a time 
when global competitiveness in biomedical research is intensifying, and 
our global competitors are spending more funding to advance their own 
biomedical research efforts, can you discuss the ramifications of 
reducing the Federal investment in NIH?
    Answer. Reducing the Federal investment in medical research has 
many ramifications. NIH is currently the largest funder of biomedical 
research in the world, and the work it supports and conducts leads to 
advances in the diagnosis, treatment, and prevention of disease. As you 
note, NIH research also has significant economic benefits and creates 
and sustains jobs in research and development. In ``NIH's Role in 
Sustaining the U.S. Economy'', United for Medical Research, an advocacy 
organization, calculated that the $23.7 billion spent by NIH 
extramurally in the U.S. in 2011 directly and indirectly supported 
432,094 jobs. NIH funding also affects the size of the bioscience 
industry, according to the Milken Institute's 2012 report, ``Estimating 
Long-Term Economic Returns of NIH Funding on Output in the 
Biosciences''. The authors, representing an advocacy organization, 
argue that a $1 increase in NIH funding will increase the size (output) 
of the bioscience industry by at least $1.70 in that year.
    NIH's current operating budget, post sequestration, of $29.15 
billion is about 5 percent below last year's budget. In addition, in 
inflation-adjusted terms, the NIH budget has declined almost every year 
since 2003. Other countries are increasing their investment and 
threatening the U.S.'s leadership in the global life sciences industry. 
Between 1999 and 2009, Asia's share (including China, India, Japan, 
Malaysia, Singapore, South Korea, Taiwan, and Thailand) of worldwide 
R&D expenditures grew from 24 percent to 32 percent, while U.S. R&D 
expenditures declined from 38 percent to 31 percent. In addition, the 
European Commission has recently urged its member nations to increase 
substantially their investment in research, recommending budgets of 80 
billion euros ($108 billion) in 2014-2020, a 40-percent increase over 
the previous seven year period.
    As other countries continue to devote a larger share of their 
annual budgets to R&D, it will be essential for the U.S. to continue to 
invest in biomedical research, training, and infrastructure. These 
investments--critical components in the ``engine of innovation''--will 
be needed to keep the U.S. in the position of worldwide leader. A 
sustained commitment to biomedical research, will allow NIH to keep up 
the pace of advancements in the treatment, diagnosis, and prevention of 
disease and in the improvement of the public health and for the U.S. to 
maintain its global lead in biomedical innovation.
    Question. Dr. Collins, diseases such as Alzheimer's, cancer, 
diabetes, and heart disease affect millions of Americans and cost 
hundreds of billions of dollars to treat each year. We all know people 
who have been impacted by each of these diseases and how important the 
development of preventive measures, diagnostic tools, and new 
treatments are. Yet recent estimates for this year project that the NIH 
will fund the fewest number of new and competing research projects 
since 1998--the first year of the doubling of the NIH. What steps are 
being taken to ensure that we continue to make progress against these 
and other diseases?
    Answer. NIH is operating at a program level of $29.15 billion in 
fiscal year 2013, a decrease of about 5 percent from fiscal year 2012. 
Despite this reduction, NIH remains committed to funding outstanding 
science and will continue to strive to find new, more effective ways to 
prevent, treat, and cure human diseases. NIH also remains committed to 
supporting the other critical elements of our mission, namely training 
and development of talented researchers and maintaining a 
technologically advanced scientific infrastructure.
    The sequester is having real effects on our ability to support both 
new and competing research projects as well as non-competing 
continuation awards. Although NIH is likely to make fewer competing 
awards in fiscal year 2013, we will be trying to keep the average size 
of competing awards constant at fiscal year 2012 levels. Most non-
competing continuation awards that have already been made in fiscal 
year 2013 were funded up to 10 percent less than the previously 
committed level. Although we may be able to make some adjustments 
during the year depending on the final level of each NIH Institutes and 
Centers' (ICs) appropriation, we will not be able to restore them to 
the previous level. Finally, new research infrastructure and core 
facilities are now ready for use, but without support for researchers 
who can take advantage of these resources, their productivity will not 
be fully realized.
    NIH will be strategic in deploying its resources in fiscal year 
2013 to achieve continued success in addressing the public health 
challenges of today and tomorrow including those you reference in your 
question. For example, to advance the progress of research on 
Alzheimer's disease, NIH will enable rapid sharing of data, disease 
models, and biological specimens, and it will promote the building of 
new multidisciplinary translational teams and create both physical and 
virtual sites where these teams can operate. NIH will also establish 
new public-private partnerships to speed drug development by 
repurposing abandoned compounds. NIH's Cancer Genome Atlas (TCGA), a 
joint effort of the National Cancer Institute (NCI) and the National 
Human Genome Research Institute (NHGRI), is a publicly accessible 
database that is opening new avenues for the identification of useful 
biomarkers and the development of targeted therapies. Among efforts in 
diabetes research, NIH will work to translate the important findings of 
controlled clinical trials for diabetes prevention or treatment into 
approaches that are effective, affordable, safe, and sustainable in 
real world settings. For heart disease, NIH is funding studies of the 
cellular and molecular mechanisms underlying large conduit-artery 
stiffening in hypertension and the examination of the temporal 
relationship between arterial stiffening and the development of 
hypertension in animal models.
    Using a priority setting process that strikes a dynamic balance 
between multiple factors, including ongoing and newly emerging public 
health needs, scientific opportunities, responses to unexpected 
scientific findings, and the need to sustain longer-range workforce and 
infrastructure development, NIH is able to support all of our mission 
areas. This process and the continuous monitoring and evaluation of 
research portfolios help ensure an ever-increasing understanding of 
basic biological functioning and the application of that understanding 
to the amelioration of disease burden. Nevertheless, decreased funding 
will limit NIH's ability to fund all of the most promising scientific 
ideas and affect the pace of the advances we generate in the treatment, 
diagnosis, and prevention of disease and in the improvement of the 
public health.
    Question. The fiscal year 2014 budget request proposes a multi-
agency reorganization of science, technology, engineering, and 
mathematics (STEM) education, which includes nine consolidations of 
NIH-related STEM programs to other agencies. What is NIH's plan with 
respect to the STEM education proposal?
    Answer. The fiscal year 2014 President's budget proposes to 
consolidate a number of science education programs under the Department 
of Education, the National Science Foundation, and the Smithsonian 
Institution. NIH staff have participated in preliminary transition 
planning discussions with representatives in those three agencies, and 
we are preparing for phase out of those programs. While K-12 science 
education is important, it is not a core NIH function given our focus 
on training the scientific workforce at the undergraduate, graduate, 
and doctoral levels.
    Question. NCATS' Learning Collaborative has incorporated resources 
from the NIH, a State university, and a nonprofit advocacy organization 
to develop new therapeutics for blood cancers. It is my understanding 
that this public-private collaboration was made easier by using a 
Collaboration Research and Development Agreement (CRADA). Do you expect 
NCATS to continue to use CRADAs in future collaborations?
    Answer. A Collaboration Research and Development Agreement (CRADA) 
is a useful tool for formalizing collaborations between intramural NIH 
scientists and university and industry scientists, and NCATS is 
utilizing this agreement type for many of its collaborations with for-
profit and non-profit organizations. NCATS anticipates continued usage 
of the CRADA mechanism, due to the collaborative nature of many of 
NCATS programs.
    Question. Do any changes need to be made to allow for the NIH to 
better leverage the benefits of CRADAs?
    Answer. While there are various mechanisms that support 
collaborations between companies and NIH intramural scientists, the 
CRADA is the only mechanism that permits the NIH to offer an upfront 
option to companies to license inventions that may be made within the 
scope of the collaboration agreement, and it also permits the 
collaborating company to provide funds to the NIH in support of the 
research. Over the last few years, the number of CRADA collaborations 
has steadily increased with new inventions being developed as a result 
of these critical scientific relationships. Currently, NIH is 
developing an online system that will tailor the CRADA terms to the 
specific needs of the collaboration and streamline the negotiation and 
implementation processes. As NCATS and other ICs explore innovative 
collaborative relationships with the private sector, NIH is flexible in 
adapting CRADAs to meet those programmatic needs.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby

    Question. The budget proposes a government-wide realignment of 
Federal science, technology, engineering, and mathematics (STEM) 
education programs. Dr. Collins, do you support the Office of 
Management and Budget's proposal to move nine of the National 
Institutes of Health's (NIH) STEM education programs to other agencies?
    Answer. The NIH supports the proposal in the fiscal year 2014 
President's budget to consolidate K-12 science education programs under 
the Department of Education, the National Science Foundation, and the 
Smithsonian Institutions. NIH staff are participating in initial 
transition planning discussions with representatives in those three 
agencies, and we are considering phase out of those programs. While K-
12 science education is important, it is not a core NIH function given 
our focus on training the scientific workforce at the graduate and 
doctoral levels.
    Question. Without Congressional approval, NIH could still move 
forward to consolidate STEM education programs within NIH. Do you think 
you will move in that direction should Congress not act on the 
government-wide realignment?
    Answer. The NIH is supportive of efforts to improve coordination of 
Federal science education programs consistent with the President's 
desire to take action to improve student outcomes. The NIH is reviewing 
its K-12 science education programs in light of reorganization and 
consolidation of STEM education proposed in the fiscal year 2014 
President's budget, but cannot speculate on a scenario where Congress 
does not act on the government-wide proposal.
    Question. Dr. Collins, the budget request proposes a new diversity 
program in the Common Fund called NIH Building Infrastructure Leading 
to Diversity (BUILD). The budget justification states that the program 
would support initiatives to strengthen the infrastructure of 
``comparatively under-resourced institutions.''
    What are the eligibility criteria for this proposal?
    Answer. NIH intends for BUILD awards to involve partnerships from 
multiple types of institutions, but only those that are referred to as 
Primary Institutions would submit applications. Primary Institutions, 
the applicant organization, are intended to be those that have the 
primary responsibility for implementation of the project and for 
management of the award. NIH intends for Primary Institutions to be 
baccalaureate-granting colleges/universities that receive less than 
$7.5 million (total costs) in NIH research project grants (RPG) 
(average of fiscal years 2010-2012) and have a pool of undergraduate 
students, at least 25 percent of whom are supported by Pell grants. The 
BUILD Primary Institution eligibility criteria are intended to target 
funds to relatively under-resourced institutions (less than $7.5 
million in NIH RPG funding) with a demonstrated commitment to students 
from diverse backgrounds that have been historically underrepresented 
in the biomedical research workforce. The intended requirement that 
BUILD institutions have a substantial pool of students from 
disadvantaged backgrounds (at least 25 percent must be Pell grant 
recipients) is based on the recognition that (1) many students from 
economically disadvantaged backgrounds are underrepresented in the NIH 
workforce in the fields of biomedical, behavioral, and clinical 
research, and (2) institutional commitment to these students often 
comes at the expense of investments in research infrastructure.
    Primary Institutions will be encouraged, but not required, to 
develop appropriate partnerships in order to optimally position 
themselves to provide a rigorous environment for research training. 
Partnerships involving a Primary Institution and one or more of the 
following institution types are encouraged:
    Pipeline Partner Institutions are intended to be 2- or 4-year 
undergraduate institutions with students that will enrich and expand 
the pool of students eligible for BUILD scholarships. Research Partner 
Institutions are intended to be research intensive institutions with 
committed investigators able to serve as effective research mentors for 
BUILD scholars. Research partnerships are intended to expand education 
and research opportunities available to BUILD scholars, work with 
Primary Institutions to develop innovative curricula, and provide 
sabbatical opportunities to faculty from Primary Institutions. Academic 
institutions, government institutions, industry, and nonprofit research 
institutions may all be considered as potential Research Partners. 
Graduate/Medical Partner Institutions are intended to be medical, 
dental, or graduate research institutions with no undergraduate program 
but with a pool of doctoral-level students engaged in research and/or 
planning a research career, and less than $7.5 million (total costs) 
through research project grants (average of fiscal years 2010-2012). 
Primary Institutions and Graduate/Medical Partner Institutions are 
intended to work collaboratively to provide joint programs for both 
undergraduate and graduate students.
    In addition to the BUILD initiative, the NIH Common Fund's 
``Increasing the Diversity of the NIH-Funded Workforce'' program 
includes two other initiatives: the National Research Mentoring Network 
(NRMN) and the Coordination and Evaluation Center (CEC). The NRMN is 
intended to facilitate the development of robust mentoring 
relationships by coordinating nationwide pairings of scientific leaders 
and early career scientists (undergraduate students through junior 
faculty members) who may benefit from additional mentoring, including 
but not limited to individuals from underrepresented backgrounds. The 
CEC is intended to serve as a centralized hub to enable the integration 
of BUILD and NRMN with existing programs, assessing the impact of the 
BUILD and NRMN initiatives from the earliest stages of implementation 
to provide early indications whether the novel approaches implemented 
by BUILD and NRMN awardees are having a meaningful effect. NIH intends 
for both the NRMN and CEC to be open to any institution within the 
United States, including academic institutions, nonprofits, and 
professional organizations.
    Question. How many institutions do you propose funding with fiscal 
year 2014 funds?
    Answer. In fiscal year 2014, we expect to support approximately ten 
Primary Institutions within BUILD, each of which will be encouraged to 
form partnerships with other institutions as appropriate. In addition, 
we expect to support one institution within NRMN, and one institution 
within CEC. The number of institutions supported will be contingent 
upon availability of funds and receipt of a sufficient number of 
meritorious applications.
    Question. How much do you expect the awards to be?
    Answer. Details of the anticipated budgets for BUILD, NRMN, and CEC 
will be provided in the Funding Opportunity Announcements for these 
initiatives, which are expected to be released in the fall of 2013. As 
described in a presentation to the NIH Advisory Committee to the 
Director (http://acd.od.nih.gov/Diversity-in-the-
Biomedical-Workforce-Implementation-Plan.pdf), the entire ``Increasing 
Diversity of the NIH-Funded Workforce Program'' budget is planned to 
average approximately $50 million per year. The majority of these funds 
are intended to go towards the BUILD initiative.
    All anticipated award budgets are contingent upon the availability 
of funds and the receipt of a sufficient number of meritorious 
applications.
    Question. Could you please provide additional details beyond those 
provided in the Funding Opportunity Announcement, related to the 
expected collaboration between the Primary, Pipeline, Research and 
Graduate/Medical Partner institutions? (OD/Common Fund)
    Answer. NIH intends for BUILD Primary Institutions to be 
encouraged, but not required, to partner with Pipeline Partners, 
Research Partners, and/or Graduate/Medical Partner Institutions. The 
intent of encouraging these partnerships is to provide the best 
research training environment for students involved in the BUILD 
program. Partnerships with Research Partners would allow students from 
under-resourced institutions to participate in robust research 
experiences that are unavailable at their home institutions. 
Participation in mentored research experiences is a critical factor in 
determining whether undergraduate students choose to pursue a research 
career; therefore, engaging students from underrepresented backgrounds 
in meaningful research experiences is anticipated to have a major 
impact on the diversity of the biomedical research workforce. Primary 
Institutions and Research Partners are intended to also work together 
to develop novel curricula, and faculty from Primary Institutions are 
intended to have the opportunity to pursue sabbatical activities at 
Research Partner Institutions. Partnering with Pipeline Partner 
Institutions will enrich the pool of students eligible to participate 
in the BUILD programs, so that students at 2- or 4-year colleges (such 
as community colleges) can benefit from research training experiences 
not available at their home institutions. Similarly, partnerships with 
Graduate/Medical Partner Institutions are intended to also expand the 
pool of BUILD-eligible scholars by providing additional research 
experiences to doctoral-level students at these institutions. NIH 
intends for Graduate/Medical Partner Institutions to include 
Historically Black Medical/Graduate Schools, which have a rich history 
of training students from underrepresented backgrounds and have a 
robust pool of students who may benefit from BUILD activities.
    Question. Dr. Collins, you stated at the hearing that while the 
Administration has proposed an overall goal of mapping the human brain, 
there are no specific scientific details or timeline you can put 
forward at this time. While I understand that you expect fiscal year 
2014 to be a scientific planning year, it is critical that the 
Appropriations Committee has a full understanding of the goals and 
timeframe of this project before funding is appropriated. Therefore, 
can you please provide the subcommittee with the following information:
    The BRAIN Initiative has no clearly defined goals or endpoint. When 
do you expect to have a scientific framework in place to answer these 
critical questions?
    Answer. NIH is undertaking a rigorous scientific planning process 
to determine the scientific aims of the NIH component of the Brain 
Research Through Advancing Innovative Neurotechnologies (BRAIN) 
Initiative, which is anticipated to include a plan for timetables and 
milestones. As part of this process, members will consult the 
scientific community, patient advocates, and the general public to 
ensure that this plan is informed by a broad and inclusive input. Final 
recommendations are anticipated in the summer of 2014, at which time 
the NIH will be able to comment on the scientific framework.
    Question. How long do you estimate mapping the human brain will 
take?
    Answer. The goal of the BRAIN Initiative is not actually to map the 
brain, per se, but rather to accelerate the development and application 
of new technologies that will enable researchers to produce dynamic 
pictures of the brain that show how individual brain cells and complex 
neural circuits interact at the speed of thought. These technologies 
will open new doors to explore how the brain records, processes, uses, 
stores, and retrieves vast quantities of information, and shed light on 
the complex links between brain function and behavior. The group 
advising the NIH on the scientific framework for the BRAIN Initiative 
has been asked to articulate the short, mid, and long term objectives 
required for achieving these aims.
    Question. What goals do you expect to accomplish in 1, 3, and 5 
years?
    Answer. It is premature to speculate on the accomplishments in the 
absence of a strategic plan outlining the scientific goals of the 
Initiative.
    Question. Do you expect the Department of Defense and the National 
Science Foundation to continue to financially support this project for 
the duration?
    Answer. NIH cannot comment on the financial commitments of the 
other agencies. However, given the different perspectives and strengths 
of each agency, NIH sees much benefit in having other agencies 
involved.
    Question. What specific role will each Federal agency contribute to 
this project?
    Answer. In general, NIH will develop new tools, training 
opportunities, and other resources. The Defense Advanced Research 
Projects Agency (DARPA) intends to explore applications--such as a new 
generation of information processing systems and restoration 
mechanisms--that dramatically improve the way we diagnose and treat 
soldiers suffering from post-traumatic stress, brain injury, and memory 
loss. The National Science Foundation (NSF) has expressed a commitment 
to supporting research that spans physical, biological, social, and 
behavioral sciences. Moving forward the agencies will work in close 
collaboration to ensure that their efforts are complementary and 
leverage the unique missions of each; ultimately catalyzing an 
interdisciplinary effort of unprecedented scope.
    Question. It has been reported that the first several years of the 
program will emphasize the development of technologies. However, this 
approach has been criticized and some neuroscientists have said that 
money would be better spent by first figuring out what needs to be 
measured and then determining the best means to measure them. How do 
you respond to this critique?
    Answer. The group advising the NIH on the scientific framework for 
the BRAIN Initiative has been asked to review the neuroscience 
landscape in order to determine the opportunities, challenges, and 
impediments in neuroscience research. It is precisely through this 
analysis that they will indeed assess what needs to be measured or what 
is missing in order to focus the investment in promising areas of 
research.
    Question. The European Union (EU) has a similar initiative called 
the Human Brain Project. How is the BRAIN Initiative different than the 
EU program?
    Answer. The EU's Human Brain Project and the BRAIN Initiative share 
the broad goal of advancing the understanding of the brain and its 
diseases. They also both recognize that technological opportunities are 
emerging to accelerate progress toward that goal. However, the two 
initiatives differ in their emphasis. The European Project emphasizes 
the development of informatics and computer infrastructure to 
systematically integrate all available data into unifying models of the 
brain. The BRAIN Initiative will focus on the development of tools that 
will transform our ability to gather new data, heretofore impossible to 
acquire, that will advance understanding of how millions of brain cells 
work together in circuits that enable us to think, act, and sense the 
world. That said, it is important to emphasize that the EU Project is 
new, multi-faceted, and will develop over time, and the BRAIN 
Initiative is in its early formative stages. As the BRAIN Initiative 
Working Group develops plans for the BRAIN Initiative, including how to 
analyze and disseminate the data it generates, the group is building 
bridges to the EU Project and to other projects outside of the U.S. 
government to take advantage of all possible opportunities for synergy.
    Question. Do you expect collaboration with the EU on the ultimate 
goal of mapping the brain in its entirety?
    Answer. As part of the working group's charge, they have been asked 
to identify areas in which collaboration with others (i.e. foundations, 
industry, other agencies) would result in either complementary 
activities or the leveraging of efforts. EU efforts will be considered 
in this analysis.
                                 ______
                                 
             Questions Submitted by Senator Lamar Alexander

    Question. You testified that sequestration caused the National 
Institutes of Health (NIH) to cut 700 extramural grants. Was intramural 
grant funding similarly affected? If so, are extramural and intramural 
on the same ``playing field?'' It is my understanding that extramural 
grants must go through a competitive peer-review process, which might 
not be the case for intramural grants.
    Answer. The NIH Intramural Research Program has been subjected to 
similar cuts due to sequestration as extramural grants. The cuts in 
intramural and extramural research similarly affect hiring, purchase of 
equipment and supplies, scientific travel, etc. In addition, some 
clinical trials conducted through extramural research are being 
delayed, and reductions in intramural research will cause approximately 
750 fewer new patients to be admitted to study protocols at the NIH 
Clinical Center. All NIH intramural principal investigators undergo 
rigorous peer review at least once every 4 years by outside scientific 
experts whose advice affects the resources allocated to them. These 
experts are members of the scientific community who receive extramural 
grants, and they are thus in a position to compare the intramural 
research with research that is funded by extramural grants. Intramural 
scientists do not, however, receive actual grants but rather compete 
for and receive internal funding and resources for scientific programs 
and projects, thus making direct comparisons in numbers of grants 
difficult.
    Question. According to your testimony, an average of 15-16 percent 
of grant applications to NIH submitted actually receive funding.
    Are all grant applications submitted included as part of this 
statistic or do are only those grants that pass a minimal standard 
initial screening process included?
    Answer. The National Institutes of Health (NIH) reports success 
rate statistics http://report.nih.gov/NIHDatabook/Charts/
Default.aspx?showm=Y&chartId=124&cat
Id=13 on the RePORT Web sites for various grant application types. The 
success rate in fiscal year 2012 for research project grants was 18 
percent, and it is projected that the success rate for fiscal year 2013 
will decline. Decreases in the Success rates are tied to availability 
of funding and the number of applications received, thus the overall 
growth in the number of applications reduces the success rate.
    The success rate describes the percentage of grant applications 
accepted for peer-review that were subsequently funded. A small 
fraction of applications submitted to NIH are not accepted for review 
for various reasons, and thus, are not included in the success rate 
calculation. Examples would include if the applicant institution is 
ineligible for the funding program for which it has applied, or does 
not have active registrations in the United States System for Award 
Management and/or NIH's Electronic Research Administration (eRA) 
Commons. Some applications are not accepted because they are missing 
required information or violate application formatting requirements. 
Finally, a small number of applications are submitted that describe 
research projects that are virtually identical to applications 
previously reviewed, or do not fall within NIH's mission, and are not 
accepted for review.
    Question. Of the total number of grant application submitted, what 
percentage are such that, even with unlimited funding, would not be 
worthy of funding? For what reasons would they be excluded?
    Answer. Most grant applications submitted to the NIH are from 
recognized scientific experts and many are worthy of funding. 
Nevertheless, it is desirable to maintain a highly competitive process 
to identify the best science to support with the resources available. 
As part of the initial peer review process, reviewers have the ability 
to identify a particular application as Not Recommended for Further 
Consideration, if it lacks significant and substantial merit; presents 
serious ethical problems in the protection of human subjects from 
research risks; or presents serious ethical problems in the use of 
vertebrate animals, biohazards, and/or select agents. Applications 
designated as NRFC do not proceed to the second level of peer review 
(National Advisory Council/Board) because they cannot be funded. This 
is a very rare event, and all other applications are considered to have 
been recommended by the initial review group as eligible for funding. 
The Institutes and Centers typically regard applications that have been 
assigned Overall Impact Scores better than the 33 percentile to be 
worthy of consideration for funding. However, each NIH Institute and 
Center (IC) may fund applications that do not meet this threshold, if 
they can establish high program relevance. Indeed, the success rate for 
Research Project grants reached 32 percent during 1999 to 2001; 
however, the high success rate is tied to the relatively low number of 
applications received. For example, in 1999, NIH received about 26,000 
applications, compared to the over 50,000 received in 2012.
    Question. How is NIH working with private foundations regarding 
young investigator awards? What percent of young investigator awards 
are being funded by NIH?
    Answer. NIH identifies New Investigators as those who have not 
previously competed successfully as the Project Director or Principal 
Investigator for a substantial NIH independent research award, e.g., an 
investigator-initiated R01 Equivalent Grant (R01, DP2 or R37). It is 
the goal of NIH to support New Investigators on new, R01 equivalent 
awards at success rates comparable to those of established 
investigators submitting new or Type 1 applications. In fiscal year 
2012, NIH awarded 1,286 competing R01 equivalent grants to New 
Investigators, for a success rate of 13 percent. There were 2,429 
comparable awards made to established investigators, for a success rate 
of 15 percent.
    NIH has a novel program for intramural scientists that is 
coordinated collaboratively with the Lasker Foundation. The Lasker 
Clinical Research Scholars Program supports a small number of 
exceptional clinical researchers in the early stages of their careers 
to promote their development as independent investigators. Scholars 
receive 5 to 7 years of support as an independent principal 
investigator in the NIH Intramural Research Program, followed by the 
competitive opportunity for additional years of financial support, 
either at the NIH or at an extramural research institution.
    Question. The National Cancer Institute (NCI) assembled a list of 
24 questions that should engage scientific community in debate and 
further advancements in cancer research. What is the timeline for 
measurable outcomes for the NCI Provocative Questions program?
    Answer. The Provocative Questions Initiative (PQI) has lofty goals 
but it is less than 2 years old, so the outcomes that can be measured 
now are largely procedural and subjective. The PQI was designed to 
engage the scientific community in efforts to identify important and 
often long-standing questions in cancer research--e.g., how obesity 
contributes to the development of cancers or why some cancers respond 
to specific drugs when others do not--and to address them 
experimentally, using new methods and new information. Part of the 
motivation was to encourage the research community to take risks and 
address important problems, even in this time of limited funding and 
low success rates. The ultimately desired outcomes of the PQI will be 
answers to at least some of the questions and applications of the 
answers to the ways in which cancers are prevented, diagnosed, and 
treated. But such outcomes cannot be expected for at least 5 to 10 
years.
    Other aspects of the PQI--its attractions for the cancer research 
community and its capacity to generate interest and exciting ideas--can 
be measured, however, even at this early stage. For instance, the PQI 
was designed to stir imaginative, inter-disciplinary thinking by asking 
working scientists, rather than NCI program directors, to develop the 
Provocative Questions. As measures of the enthusiasm generated by this 
project, we have kept track of the many PQI workshops that the NCI has 
conducted throughout the country, bringing scientists from different 
disciplines together to propose and discuss questions; and we have 
observed the heavy traffic on our PQI Web site, where questions are 
posted and debated. When we selected twenty-four questions to be 
addressed in the first round of competition for grants, we received 
over 750 applications, indicating a high level of interest and we 
funded slightly more than fifty of the best applications. The NCI is 
currently evaluating a second set of applications received in response 
to Provocative Questions.
    Question. Please address any overlap between the NIH Common Fund 
and the NIH National Center for Advancing Translational Sciences. How 
are these two areas coordinating efforts?
    Answer. By design, the Common Fund is not separate from the ICs. 
Scientific oversight for each Common Fund Program is provided by two or 
three IC Directors who serve as co-chairs. Requests for applications 
(RFAs) are issued from the IC of one of the co-chairs and day-to-day 
and long-term program oversight is provided by staff from the co-
chairs' ICs. In addition, each program has a trans-IC Working Group 
composed of program staff from as many ICs as are interested in 
participating. Successful coordination of this distributed management 
model is the responsibility of the Office of Strategic Coordination in 
the Division of Program Coordination, Planning, and Strategic 
Initiatives (DPCPSI), NIH Office of the Director (OD). There are 
several programs within the National Center for Advancing Translational 
Sciences (NCATS) that originated from, and are currently being funded, 
either fully or partially, by the Common Fund. These include the 
Bridging Interventional Development Gaps (BrIDGs) program; the NIH 
Chemical Genomics Center (NCGC), which is part of the Common Fund's 
Molecular Libraries and Imaging program; the Tissue Chips for Drug 
Screening program and the Discovering New Therapeutic Uses for Existing 
Molecules program, which are both part of the Common Fund's Regulatory 
Science program; and the Extracellular RNA Communication program. For 
all of these initiatives, there is ongoing coordination between NCATS 
and Common Fund staff, with guidance from trans-NIH working groups. 
Complementarity between the Common Fund and NCATS in how these programs 
are currently conceptualized, managed, and led on behalf of the trans-
NIH community.
    The fiscal year 2014 President's budget requests additional funding 
for NCATS so that support for several of these programs can be shifted 
from the Common Fund to NCATS.
    Question. One of the newest entities within the NIH is the NCATS. 
Could you provide the committee with an update on some of NCATS' 
current activities and planned expenditures in fiscal year 2014? I am 
especially interested in the Clinical Translational Science Awards 
(CTSAs) program, which I believe the Institutes of Medicine is 
currently reviewing at NIH's request. Vanderbilt University in 
Nashville is the coordinating center for the 60 research institutions 
linked by this program, which supports local and national research 
communities to improve the quality and efficiency of all phases of 
translational research. Going forward, how do you envision building on 
the work of CTSA recipients to complement other NIH initiatives in 
translational science? How do you see the CTSA program working with 
Foundations, patient advocacy groups and industry?
    Answer. To bring the benefits of science more quickly into patient 
care, the NCATS was formed with the mission to catalyze the generation 
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. 
NCATS' mission includes strengthening the entire spectrum of 
translational research--defined broadly to include the early steps 
necessary to develop new therapeutics, devices and diagnostics from 
basic discoveries, the steps necessary to establish real world 
efficacy, and the research needed to improve the practical 
implementation and dissemination of improved approaches to care.
    NCATS will utilize a number of programs to accomplish its mission 
across this translational spectrum. Extending the success of the CTSA 
program in transforming the local and regional environment for 
translational research to, in turn, transform the national environment 
for translation will be a central component. In order to accomplish 
this transformation across a broad spectrum of diseases and conditions, 
NCATS will focus on collaboration in and across all of its programs. 
Key partners will include, but are not limited to, other NIH 
Institutes, Federal agencies, patient advocacy groups, professional 
societies, foundations, healthcare systems, and a wide range of 
commercial entities. NCATS will leverage and build on existing 
relationships with many foundations, patient advocacy groups and 
industry, as collaborators, advisors, committee members and program 
partners.
    NCATS engaged the Institute of Medicine (IOM) to review the CTSA 
program and provide recommendations for any changes needed in the 
program. The report was released at the end of June and NCATS is 
reviewing the recommendations of this group as we work to evolve the 
CTSA program within NCATS.
                                 ______
                                 
                Questions Submitted by Senator Mark Kirk

    Question. BrainGate is a promising technology. How does the 
National Institutes of Health (NIH) plan to integrate promising 
technologies like BrainGate--and other existing stroke research 
priorities--with the proposed Brain Research through Advancing 
Innovative Neurotechnologies (BRAIN) Initiative?
    Answer. The BrainGate neural interface system is a promising type 
of brain-computer interface intended to put prosthetic arms and other 
assistive technologies under the control of people who are disabled 
because of a stroke or other neurological disorder. Using BrainGate in 
a controlled laboratory setting, a paralyzed woman was able to move a 
robotic arm and take a sip of coffee on her own for the first time 
since she had been paralyzed more than 14 years earlier. BrainGate 
consists of sensors implanted in the brain that monitor signals from 
nerve cells in a brain area that controls movement, and computer 
software and hardware that translate these signals into digital 
commands for assistive devices. A clinical trial, funded in part by the 
NIH, is evaluating the safety and feasibility of this device.
    The BRAIN initiative will advance the prospects for more effective 
brain computer interface devices in two ways. First, BRAIN will develop 
tools that will transform researchers' capabilities to monitor larger 
numbers of brain cells, in a less invasive manner, more stably over 
time. This addresses major limitations of the current generation of 
brain computer interfaces, which monitor relatively few cells and rely 
upon invasive electrodes that often do not maintain a stable signal 
over time. Second, with the tools from BRAIN in hand, researchers will 
learn to better understand the ``neural code'' by which brain circuits 
control movement and perceive the environment. This will enable the 
design of devices that interface with brain circuits more effectively 
to provide precise and natural movement control and sensory feedback.
    The potential for extraordinary long-term benefits of the BRAIN 
Initiative is tantalizing, with transformative technologies for 
recording nerve cells now in use or on the horizon, including those 
that rely on optical signals. However, these technologies are currently 
not suitable for use in humans, and laboratory research in animals, 
including those with much simpler brains, will initially be a focus of 
BRAIN. NIH is continuing to support the near-term development of brain 
computer interfaces, such as BrainGate, as we also invest through the 
BRAIN Initiative in research that will revolutionize the understanding 
of the brain and its disorders in the future.
    Question. Rehabilitation research is cross-cutting within NIH. What 
is NIH doing to prevent duplication in research?
    Answer. NIH's rehabilitation research efforts include a range of 
studies from developing next generation prostheses and assistive 
devices, to optimizing physical, cognitive, and combination drug 
therapies. A number of NIH Institutes and Centers (ICs) support 
extensive research related to medical rehabilitation.
    Although multiple ICs are involved, they proactively work to 
coordinate their activities and prevent duplication of efforts. For 
example, the Eunice Kennedy Shriver National Institute of Child Health 
and Human Development's National Center for Medical Rehabilitation 
Research (NCMRR) supports research needed to enhance the health, 
productivity, independence, and quality-of-life of people with 
disabilities. The Center's role includes coordination of medical 
rehabilitation research, and promoting research specific to the health 
related problems of people with disabilities in order to capitalize on 
advances occurring in the biological, behavioral, and engineering 
sciences. The Center's work has been aided by a blue ribbon panel 
formed in 2011 to focus on medical rehabilitation research at NIH. The 
panel conducted an analysis of rehabilitation science activities within 
the NCMRR and across the NIH to identify the most promising research 
opportunities which was reported to the National Advisory Child Health 
and Human Development Council.
    In addition, NIH has an established record of identifying 
scientific areas of potential overlap and developing trans-NIH 
programs, activities, and policies to optimize the strengths and 
expertise within each of the ICs and to ensure the complementarity of 
their programs and activities. The Division of Program Coordination, 
Planning, and Strategic Initiatives (DPCPSI) in the Office of the 
Director works closely with the NIH Institutes and Centers (ICs) to 
plan and coordinate trans-NIH research cross-cutting activities. As 
part of this process, DPCPSI will work with all relevant ICs to conduct 
a portfolio analysis designed to identify scientific gaps and areas of 
sufficient investment.
    DPCPSI's Office of Portfolio Analysis provides consultation and 
training to NIH program staff in the use of portfolio analysis tools 
that allow IC staff to identify gaps in specific research portfolios 
and areas that are adequately funded across ICs. Such evaluation tools 
provide data to enhance prioritization efforts of current and emerging 
areas of research, and also prevent unnecessary overlaps and 
duplication of effort.
    Administrative processes are also in place to monitor for 
scientific overlaps in funding opportunity announcements (FOAs) and in 
grant applications. At the FOA stage, the new Guide Publishing System 
allows ICs to review of funding opportunity announcements prior to 
publication. When grant applications are received, duplicative 
proposals can be identified at the receipt and referral stage and at 
the peer review stage. After review, meritorious applications are 
checked for other sources of support, including all existing and 
pending financial resources, whether Federal, non-Federal, commercial 
or organizational, to determine whether there may be budgetary, 
scientific, or commitment overlap. This step is key to identifying and 
eliminating duplicative proposals.
                                 ______
                                 
               Questions Submitted to Dr. Story C. Landis
                Question Submitted by Senator Tom Harkin

    Question. Dr. Landis, when you add up the contributions from your 
private sector partners--the Allen Institute for Brain Science (at 
least $60 million/year), the Howard Hughes Medical Institute (at least 
$30 million/year), and others--they're planning to contribute 
approximately the same amount or more as the President is requesting. 
Do you expect the same situation in future years of the initiative?
    Answer. Each partner has a long-standing commitment to neuroscience 
research and we do not anticipate that their contributions to the Brain 
Research through Advancing Innovative Neurotechnologies (BRAIN) 
Initiative will be a one-time event. However, details of the initiative 
are still under development as part of a rigorous scientific planning 
process, for which final recommendations are anticipated in the summer 
of 2014. This plan will be widely shared with both the public and with 
our BRAIN Initiative partners.
                                 ______
                                 
              Questions Submitted to Dr. Richard J. Hodes
               Questions Submitted by Senator Jerry Moran

    Question. Dr. Hodes, the RAND Corporation recently released a 
report that found that the cost of caring for all Americans with 
dementia in 2010 was between $157 billion and $215 billion. By 2030, 
the number of Americans with dementia is expected to more than double. 
A few statistics:
  --Medicaid payments alone are 9 times higher for those with 
        Alzheimer's compared to those without the disease.
  --64 percent of Medicare beneficiaries in nursing homes over 65 years 
        old have Alzheimer's disease or other dementia and Medicare 
        pays approximately $11 billion a year for their care.
  --Each dementia case costs between $41,000-$56,000 a year.
    We know that these numbers will only increase as our population 
ages. I support the National Institutes of Health (NIH) for many 
reasons--the impact to health being paramount. But another key 
component of my support is that I believe if we can find effective 
treatments for diseases like Alzheimer's and dementia, we can not only 
extend quality of life for patients, but reduce the cost of caring for 
these patients in years to come. Could you discuss some of the research 
projects the National Institute on Aging will fund if this proposal is 
approved and the impact these projects could have on our Nation's 
healthcare costs?
    Answer. Pending availability of funds, the ongoing Alzheimer's 
disease (AD) research supported by the National Institute on Aging 
(NIA) will continue in 2014, along with several recently launched 
efforts made possible with increased funding. These include:
  --Whole genome sequencing to identify new genetic variants that 
        either increase risk (risk factors) or reduce risk (protective 
        factors) for AD (in collaboration with the National Human 
        Genome Research Institute).
  --A treatment trial to test the effectiveness of intranasal insulin 
        in individuals with mild cognitive impairment or mild 
        Alzheimer's dementia on cognition and daily functioning.
  --A 5-year prevention trial to test the ability of an antibody called 
        crenezumab to bind to and clear away abnormal amounts of 
        amyloid protein in the brain and prevent cognitive decline in 
        people with early-onset AD.
  --Research to be funded in fiscal year 2013 and fiscal year 2014 
        under four 2012 Funding Opportunity Announcements supporting 
        drug discovery, development, and preclinical and clinical 
        testing for the treatment and prevention of Alzheimer's disease 
        and dementia.
    In addition, recent scientific advancement suggests that some new 
activities may be feasible. If so, we anticipate new activities in the 
following areas in fiscal year 2014:
  --Additional Drug Development and Testing.--This will include support 
        for drug repurposing and combination therapy, phase 2 (proof of 
        concept) drug trials for agents against currently known 
        therapeutic targets, and studies of possible agents against 
        not-yet-known therapeutic targets for AD.
  --Non-Pharmacological Intervention Development.--We will focus on 
        advancing non-pharmacological interventions for the cognitive 
        and behavioral symptoms of AD and the design of approaches that 
        combine pharmacological and non-pharmacological treatments.
  --Biomarkers of Disease Progression to Measure the Effects of 
        Potential Treatments.--We will test imaging and fluid 
        biomarkers for the assessment of disease-related pathology, 
        work to develop and validate sensitive measures to detect and 
        track the earliest clinical changes of AD, and develop and test 
        methods for the standardization of neuroimaging procedures and 
        data collection.
    The issue of the impact of this research on healthcare costs is 
highly complex. Alzheimer's disease treatment and care place an 
enormous financial and economic burden on patients, their families, and 
the healthcare system, as illustrated by the NIA-supported study from 
the Rand Foundation noting that the costs of caring for people with 
dementia in the United States in 2010 were between $159 billion and 
$215 billion, and could double by 2040. Estimates of cost savings 
resulting from an effective therapy need to account for a number of 
factors, including the cost of the therapy itself, which could be 
significant, or savings offset by other costs of providing care to 
those surviving patients.
    Question. Many diseases are increasingly common with older age. 
What efforts is NIH making to understand the aging process and its 
relationship to these diseases?
    Answer. Age is a primary risk factor for many disabling diseases 
and conditions, and NIH supports a robust program of research aimed at 
understanding the relationship between aging and disease and 
disability. Ongoing initiatives include:
  --NIH Geroscience Interest Group.--The NIH Geroscience Interest Group 
        (GSIG) was established in 2012 to accelerate and coordinate 
        efforts to promote further discoveries on the common risks and 
        mechanisms behind age-related diseases and conditions by 
        developing a framework that includes multiple NIH Institutes. 
        By pooling resources and expertise, the GSIG identifies major 
        cross-cutting areas of research and proposes coordinated 
        approaches to identify hurdles and envision solutions. In 
        September 2012, the GSIG sponsored a workshop on inflammation 
        and age-related diseases, and this activity has led to a 
        Funding Opportunity Announcement on the subject, co-sponsored 
        by several NIH Institutes. As a way of gaining further input 
        from the research community, a larger-scale workshop titled 
        ``Geroscience: Foundations for Delaying Chronic Disease and 
        Increasing Healthspan'' is planned for fall 2013. This two and 
        a half day forum will bring together 53 leaders from the fields 
        of aging and major chronic diseases.
  --Nathan Shock Centers on the Basic Biology of Aging.--NIH supports 
        five Nathan Shock Centers on the Basic Biology of Aging. These 
        Centers provide leadership in the pursuit of basic research 
        into the biology of aging through a Research Development Core 
        which administers small start-up funds locally, and organizes 
        national annual meetings to highlight specific areas of 
        research. In addition, each Nathan Shock Center has several 
        specialized cores that provide services to other investigators. 
        The cores are different in each Center, depending on the 
        strengths of each Institution. Funding for the Nathan Shock 
        Centers is slated for renewal in fiscal year 2015.
  --Interventions Testing Program (ITP).--This ongoing program, which 
        began in 2003, supports the testing of compounds with the 
        potential to extend the lifespan and delay disease and 
        dysfunction in a mouse model of aging. A number of 
        interventions, including foods, diets, drugs, and hormones, are 
        tested through the ITP, and some compounds, such as rapamycin, 
        have been found to increase not only lifespan, but health as 
        well. Further research is ongoing, and a parallel program has 
        been established to test interventions in the worm model 
        ``Caenorhabditis elegans''.
    Question. How might this understanding allow better treatment or 
prevention?
    Answer. A better understanding of the basic biochemical, genetic, 
and physiological mechanisms underlying the process of aging and age-
related changes will provide insight as to how these changes become 
risk factors for (or accompany) age-related disease and disability. 
This, in turn, will suggest interventions that may increase both 
lifespan and health span in older adults.
    An example of basic discovery that may suggest pathways for 
prevention of disease and disability is the exciting research being 
conducted around cellular senescence and aging. Senescent cells no 
longer divide but still function within the organism and until recently 
scientists believed that they were very rare in living organisms and 
would not play an active role in aging. However, NIH-supported 
investigators recently found that high levels of senescent cells 
actually do accumulate in many tissues in aged mice, and may be an 
early marker of cancer--in fact, the earliest marker of cancer 
described to date. In a separate study, removal of senescent cells in 
mice delayed the onset of disease-related changes in skeletal muscle, 
fat, and eye tissues. In addition, removing senescent cells later in 
the life of the mice slowed the progression of already established age-
related disorders. While research on cell cultures has long suggested 
that senescent cells have a role in aging, the nature of this 
connection in live animals was less clear. The new finding suggests 
that cell senescence may be a fundamental mechanism that drives aging, 
and provides a clear target for interventions to prevent age-related 
damage to cells and tissues.
    Question. Dr. Hodes, as a nation, we invest a significant amount of 
funding towards healthcare. What is the NIA doing--and what should the 
NIA do--to expand and translate research on prevention and wellness for 
our rapidly aging population?
    Answer. Recent NIA-supported studies conducted by the National 
Academy of Sciences have shown that although the United States spends 
more on healthcare than any other nation, Americans are in poorer 
health and live shorter lives than people in many other high-income 
countries. This health disadvantage exists across the lifespan, from 
birth to age 75. Many of the reasons behind these disparities appear to 
be behavioral and social--for example, Americans are more likely to 
engage in certain unhealthy behaviors, such as heavy caloric intake and 
behaviors that increase the risk of fatal injuries. However, even 
Americans who have health insurance, college educations, and higher 
incomes who adopt healthy behaviors appear to be sicker than their 
peers in other wealthy nations. The reasons for these disparities 
remain unclear. NIA continues to support research to determine the 
factors that contribute to premature mortality and lower disability 
adjusted life years in the United States, as well as the prospects for 
modifying such risk factors.
    In addition, NIA supports a number of studies of interventions to 
prevent disease and disability. For example, the ongoing Lifestyle 
Interventions and Independence for Elders (LIFE) Study, a major 
clinical trial comparing the effects of a moderate-intensity physical 
activity program to a health education program on prevention of 
mobility loss disability in older Americans, began in 2010. In 
addition, NIA supports a number of studies exploring the effects of 
exercise and physical activity on everything from mobility to mood and 
cognition. NIA also supports studies of a variety of interventions for 
health conditions common to old age. Ongoing studies include: the 
ASPirin in Reducing Events in the Elderly (ASPREE) trial, designed to 
determine whether the benefits of aspirin outweigh the risks in people 
over age 70; testosterone supplementation to delay or prevent frailty 
in older men; and an array of interventions for menopausal symptoms.
    Translation of research findings related to healthy aging is an 
important priority for the NIA. For example, we support 13 Edward R. 
Roybal Centers for Translational Research in the Behavioral and Social 
Sciences of Aging, which stimulate broadly based multidisciplinary 
research that improves the health, wellbeing, and productivity of older 
adults. The Roybal Centers focus on diverse topics including health and 
mobility, disease and pain management, and decisionmaking and behavior 
change.
    NIA also supports a successful program of communication and health 
education for older adults, their caregivers, and healthcare providers. 
For example, recognizing the value of exercise, the NIA partnered with 
the U.S. Surgeon General to launch its nationwide ``Go4Life'' campaign. 
This program is designed to motivate older Americans to engage in 
physical activity and exercise by becoming active for the first time, 
returning to exercise after a break in their routines, or building 
activity into daily routines. Go4Life offers exercises, motivational 
tips, and free resources to help participants get ready, start 
exercising, and keep going. The Go4Life campaign centers on an 
interactive Web site (www.nia.nih.gov/go4life), which features an 
evidence-based exercise guide in English and Spanish, exercise videos, 
and more. The initial partners include a diverse group of public and 
private Go4Life Team Members from major health and aging organizations 
and agencies, and the Institute intensified program activities in 2012.
    Further, NIA produces informative, evidence-based educational 
materials for older adults, including ``Age Pages'' in English and 
Spanish on a wide variety of topics of interest, as well as more in-
depth documents providing information and advice on an array of topics, 
including healthy nutrition, planning for retirement, and end-of-life 
care. Finally, NIA and the National Library of Medicine have created 
NIHSeniorHealth.gov, a health information Web site tailored to the 
specific cognitive and information needs of older Americans.
                                 ______
                                 
              Questions Submitted to Dr. Harold E. Varmus
               Questions Submitted by Senator Jerry Moran

    Question. Dr. Varmus, I have read several news articles about the 
impressive results being generated by the Cancer Genome Atlas project.
    What is being done to ensure that the new information being 
discovered about cancer genomes will have direct benefits for patients?
    Answer. The unprecedented wealth of data generated by the Cancer 
Genome Atlas (TCGA) is dramatically increasing our knowledge of the 
range and combination of abnormalities that may be found in cancer and 
refining our understanding of molecular pathways that control its 
malignant behavior. With the long-term goal of improving diagnostic 
precision and treatment outcomes for cancer patients, TCGA data are 
being applied to an array of projects and programs in the U.S. and 
abroad. For example, the National Cancer Institute (NCI) Cancer Target 
Discovery and Development (CTD2) Network, which is a consortium of 
investigators from many research institutions in the U.S., is 
elucidating new targets for therapeutic attack in cancer and developing 
means to inhibit these targets. TCGA data are also being used to 
explore the relationship between germline genetic variation and the 
molecular features of tumors that arise in various tissues.
    TCGA data are widely available to qualified researchers through 
public databases designed to protect patient privacy, and we are 
continually striving to improve our management of these extremely large 
datasets through enhanced computational methods. The TCGA team provides 
extensive support to researchers who access TCGA data, including step-
by-step protocols for how to locate and apply TCGA data, as well as 
preliminary data analysis to those who need assistance with 
manipulating the raw data, in an effort to maximize the efficient and 
effective use of the data. The large number of publications that use 
TCGA data (almost 400 since 2008) and the number of grant applications 
that include TCGA data (to date, more than 800) reflect the widespread 
availability and broad utilization of TCGA data by the cancer research 
community. In addition, the NCI is expanding its computational power in 
various ways to cope more effectively with the rapidly growing data 
sets from TCGA and other endeavors in cancer genomics.
    Pursuing the genetic foundations of many cancers is a vital element 
of NCI's current research, comprising a substantial proportion of the 
institute's research portfolio. A principal task in the years ahead, 
for NCI and for the entire cancer research enterprise, will be to 
capitalize on the information developed through TCGA by supporting 
additional studies that validate and extend our understanding of--and 
ability to use to diagnostic, prognostic, and therapeutic advantage--
the critical roles for specific genomic changes in tumors. Ultimately, 
these efforts can be expected to lead to more precise classification of 
cancers and more effective interventions that improve outcomes for 
patients.
    Question. For example, are the data and the methods being 
incorporated into the design of NCI's clinical trials?
    Answer. NCI has recently consolidated a number of its genomics 
initiatives--including TCGA and several pediatric cancer initiatives, 
most notably TARGET (Therapeutically Applicable Research to Generate 
Effective Treatments), as well as CTD2--into a single Center for Cancer 
Genomics. The new Center is working with other components of NCI and 
with other investigators in addition to those directly involved in TCGA 
to ensure that research findings are applied to developing new 
diagnostics and therapeutics that can be integrated into medical 
practice. For example, new therapeutic studies are now being designed 
by our clinical trials groups in conjunction with TCGA staff to match 
the genotypes of advancing cancers with targeted drugs and to seek 
genomic explanations for unexpectedly good responses to existing drugs 
or to not yet approved agents used in clinical trials; these studies 
will use methodology developed in conjunction with TCGA projects. In 
addition, several clinical trials have already been established based 
directly on TCGA data, and we expect additional trials to be initiated 
as TCGA continues to generate new information about potential targets 
for cancer treatment strategies.
    We anticipate that our growing understanding of the molecular 
events that drive cancer development and distinguish one cancer type 
from another will have a marked effect on the way future clinical 
trials are designed. The new knowledge should enable the NCI 
cooperative groups that do most of our clinical trials to run smaller, 
more precise clinical trials with greater likelihood of therapeutic 
success. In addition, we can expect an increasing number of clinical 
trials that are somewhat tumor site-agnostic: directed at molecular 
vulnerabilities that are common to cancers that may arise in different 
tissues.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby

    Question. Dr. Varmus, last year you expressed concerns about 
legislation that originally would have required the National Cancer 
Institute to spend $887.8 million of its budget on pancreatic cancer 
research. I share the concern about earmarking disease specific 
research. I believe science should dictate funding and a legislative 
mandate on disease specific research would lead to a slippery slope of 
Congress moving into the driver seat of determining how the National 
Institutes of Health (NIH) research funding is spent. That said, the 
current Administration has attempted to earmark NIH funding in the past 
for both cancer and Alzheimer's disease research.
    How can it be wrong for Congress to direct funding, but not for the 
Administration to do so?
    Answer. NIH is comprised of 27 institutes and centers (IC) mostly 
organized by specific diseases, organs, and stages of life. These 
entities come together to seek the fundamental knowledge about the 
nature and behavior of living systems and the application of that 
knowledge to enhance health, lengthen life, and reduce illness and 
disability.
    Historically, Congress has given NIH the flexibility to drive 
research and this flexibility has nurtured scientific advances and 
development of means to prevent and treat diseases more effectively. A 
baby born today can look forward to an average lifespan of nearly 79 
years, nearly three decades longer than a baby born in 1900. For 
example, U.S. cancer death rates are falling more than 1 percent each 
year. and age-adjusted death rates from heart disease and stroke have 
fallen more than 60 percent in the last half-century. Thanks to anti-
viral therapies developed by NIH funded researchers, HIV-infected 
people in their 20s can expect to live to age 70 and beyond.
    NIH will continue invest research funds based on scientific 
opportunities and public health needs. As part of the Executive Branch, 
the NIH works closely with the Administration to plan future research 
efforts. The Administration's past interest in increased spending on 
cancer research and more recent interest in Alzheimer's disease (AD) 
research both came at a time of enhanced scientific opportunity and 
public health need for progress against these devastating and common 
diseases. About half of men and a third of women in the U.S. will have 
a cancer diagnosis in their lifetimes, and cancer is the second most 
common cause of death. Moreover, research over the past three decades 
has transformed our conception of the disease, creating opportunities 
for rapid advances Thus we have learned that cancer is a disease of the 
genome, that it's not just one but many diseases, and that investments 
to use the new tools of genomics are likely to lead to rapid progress 
in the diagnosis and treatment of those several diseases. For example, 
as drugs are developed that target certain mutations, doctors will be 
able to use information about the molecular profile of a patient's 
tumor to assess whether a given drug is likely to be effective. Genomic 
knowledge can also be used to decide against a particular treatment, if 
the appropriate target mutations are not in play, thus sparing a 
patient the costs, waste of time, and side effects of a drug that is 
not likely to help them.
    The number of individuals with AD is expected to increase 
dramatically as the population ages. The U.S. Census Bureau estimates 
that the people 65 years and older will double to about 72 million 
during the next 20 years. As the population ages, the medical and 
treatment expenses associated with AD will continue to increase and 
impose a significant economic burden to society and the government. At 
the time the Administration announced the additional funding for AD, 
NIH seized the opportunities to expand on several AD advances. NIH 
supported researchers discovered that higher amounts of the brain 
amyloid deposits in dementia-free individuals were associated with an 
increased risk of developing dementia over time, making it a possible 
preclinical sign of disease even among individuals who appear mentally 
normal. In addition, NIH supported researchers developed a method of 
testing for the known biomarkers for AD in the cerebrospinal fluid. 
With these discoveries, NIH hopes to help diagnosis individuals with AD 
in order to initiate treatment efforts early and delay the progression 
of AD.
    Question. It is my understanding that you had numerous concerns 
about authorizing legislation proposed last year that would have 
specified an amount of funding for pancreatic cancer. Can you discuss 
some of those concerns?
    Answer. The National Cancer Institute (NCI) raised serious 
objections last year to a legislative proposal (a version of H.R. 733, 
filed originally on February 16, 2011, ``to provide for a Pancreatic 
Cancer Initiative''). However, our objections were directed largely 
against a new methodology that would have altered how NCI funds grant 
applications.
    In this instance, the legislation would have required that the 
Secretary of Health and Human Services convene a group, composed almost 
entirely of pancreatic cancer researchers, to recommend which grant 
applications should be funded. This would have created an unfortunate 
precedent for many groups to ask for similar privileges, a situation 
that would have been unworkable and damaging. Fortunately, this and 
several other objectionable elements were removed from H.R. 733 before 
its eventual approval as the Recalcitrant Cancers Act.
    Although we objected to the bill in question largely on other 
grounds, the NCI generally disapproves of mandates to spend specific 
amounts of money on individual cancers. This is so for several reasons. 
First, it is difficult to determine an exact number for disease-
specific spending: some studies address multiple cancers; many are 
aimed at fundamental cell processes that are relevant to most or all 
cancers; and some grants support training, technology development, and 
other infrastructural issues that cannot be classified. More 
importantly, history has supported the argument for supporting the best 
science, rather than meeting a fiscal quota for each disease type. It 
is common for studies of one type of cancer to provide unanticipated 
insights into another type or for studies of the basic features of 
cancer to illuminate our understanding of a variety of cancers. For 
example, investment in a rare disease, retinoblastoma, was critical for 
the discovery of tumor suppressor genes, a class of genes that is 
affected in essentially every cancer type. Similarly, work on an animal 
model of neuroblastoma led to the discovery of an oncogene, HER2, which 
is targeted by antibodies now widely used in the treatment of breast 
cancer. What has worked best is the support of experiments that pursue 
the most inviting scientific opportunities. Of course, the NCI is 
attentive to its patterns of spending on many types of cancer, 
especially with regard to clinical research; but rigid prescriptions 
for funding levels limit the Institute's capacity to support the most 
productive work and respond quickly to new developments in cancer 
science.

                          SUBCOMMITTEE RECESS

    Senator Harkin. The hearing of the Labor, Health and Human 
Services Subcommittee is adjourned. Thank you again all very 
much.
    [Whereupon, at 4:20 p.m., Wednesday, May 15, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]
