[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, APRIL 2, 2014

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10 a.m., in room SD-192, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Durbin, Mikulski, Moran, Cochran, 
Shelby, and Kirk.

                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
        HAROLD E. VARMUS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
        GARY H. GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG AND BLOOD 
            INSTITUTE
        STORY C. LANDIS, PH.D., DIRECTOR, NATIONAL INSTITUTE OF 
            NEUROLOGICAL DISORDERS AND STROKE
        CHRISTOPHER P. AUSTIN, M.D., DIRECTOR, NATIONAL CENTER FOR 
            ADVANCING TRANSLATIONAL SCIENCES


                opening statement of senator tom harkin


    Senator Harkin. The Appropriations Subcommittee on Labor, 
Health and Human Services, and Education, and Related Agencies 
will come to order. Good morning, everyone, and welcome. Sorry 
we are a little late. We had a vote at 10--that is all.
    Well, today will be my final Appropriations budget hearing 
for the NIH (National Institutes of Health) as the chair of 
this subcommittee. I took over this subcommittee from Senator 
Lawton Chiles in 1989. That is a long time ago it seems, a 
quarter century. I am so proud of all that we have done--all of 
us here--often on a bipartisan basis, to transform the National 
Institutes of Health into truly the jewel and the crown of 
biomedical research not only in the United States, but 
globally.
    On Tuesday, as many of you know, I was on the NIH campus to 
help dedicate the new John Porter Neurosciences building. I was 
struck as I drove around the campus by the growth and 
modernization that has taken place there in the last 25 years. 
But that physical transformation has been more than matched by 
the transformational science and discovery that has sprung from 
that campus.
    If you do not mind, a little bit of reminiscences. My first 
year as chair was the first year that we invested NIH dollars 
in an exciting new project to map the human genome, 1989. I 
will never forget. I had taken over this subcommittee and I was 
visited by Dr. James Watson, whom I had never met before, but 
of course I had read about him--the famous Nobel Prize winner--
Watson and Crick, discoverers of the double helix. And so, I 
was quite full of myself when as a freshman Senator I was 
visited by this great scientist who wanted to talk to me about 
investing in mapping and sequencing the human gene. I had no 
idea what he was even talking about at that time, but he 
brought me along a little bit, and so we were able to put a 
little bit of money into that.
    Thanks again to all that initial work. And thanks to the 
work of Dr. Collins and his colleagues at NIH. We can now 
sequence the human genome at a fraction of the cost that it 
required, and in a shorter timeframe. I might just add, there 
was a study done by the Battelle Institute. It came out last 
year and said that the U.S. Federal Government's $3.8 billion 
funding of the Human Genome Project between 1988--actually it's 
1989, but that is okay--between 1988 and 2003 drove $796 
billion in U.S. economic impact due to the growth of the 
genomics technology industry and the use of genomics in 
healthcare, energy, agriculture, and other sectors--quite a 
rate of return on investment.
    And consider this: In 1989--I remember it well in the 
1980s--HIV (human immunodeficiency virus) was a death sentence. 
Today, thanks in large part to the leadership of Dr. Anthony 
Fauci, HIV is a manageable chronic disease, and we know how to 
prevent it. Since 1989, the proportion of older people with 
chronic disabilities has dropped by nearly one-third. Cancer 
death rates in the U.S. are now falling at a rate of nearly 1 
percent each year. And each 1-percent decline saves our Nation 
nearly $500 billion. There has been near miraculous progress in 
the fight against childhood cancers with the 5-year survival 
rate for the most common type, acute lymphocytic leukemia, now 
rising to a 90-percent cure rate. That is fantastic.
    Two of our witnesses here today direct centers that did not 
exist, that were not part of NIH in 1989. The National 
Institute of Mental Health moved from SAMHSA (Substance Abuse 
and Mental Health Services Administration) to NIH in 1992, and 
this subcommittee created the National Center for Advancing 
Translational Sciences (NCATS) in 2011. And although the 
directors are not here today, I am particularly proud to have 
authored the bill that created the National Institute on 
Deafness and Communication Disorders in 1988. Again, as I said, 
we worked to elevate the Genome Research Office at that time to 
a center in 1989, and we created the National Center for 
Complementary and Alternative Medicine in fiscal year 1992. 
Looking back to 1989, my notes tell me that in 1989 a Yale 
scientist named Francis Collins led a research team to discover 
the gene for cystic fibrosis.
    How far the NIH has come in 25 years. So many Nobel Prizes. 
So many life-saving discoveries. This subcommittee has had no 
higher priority than to support NIH and the scientists all 
across America dedicated to reducing suffering and improving 
public health. So this is a bittersweet moment for me and for 
all of us who revere the work of NIH because these great 
achievements are in the past. The future leadership of NIH is 
threatened by penny wise, pound foolish thinking by too many 
here in the Congress. Most in Congress are obsessed by budget 
deficits. I am more concerned by our deficits of vision and 
ambition and leadership.
    I am proud to say that since 1989, I have either chaired or 
been the ranking member of this subcommittee. Most of that time 
with Senator Arlen Specter. We kept changing back and forth as 
the leadership of the Senate would change, more recently with 
both Senator Shelby and now Senator Moran on this committee. So 
it has been, for me, an enlightening experience, through all 
these years. I do not have a science background, a bit of an 
engineering background, but not much of science. So for me it 
has just been eye opening to see what has happened with NIH 
through all these years.
    As our Government charts a course of stagnation and 
disinvestment in biomedical research, other countries are 
surging ahead. China's government pledged to increase its basic 
research investment by a staggering 26 percent just in the last 
year and will invest more than $300 billion in biotechnology 
over the next 5 years, twice what we are planning on doing.
    So this is the context in which we consider the proposed 
funding levels for fiscal year 2015. The Murray-Ryan budget 
deal partially replaced the sequester for the coming year, and 
while I am pleased that the subcommittee has a solid top line 
figure to work with, these austere budget caps are wreaking 
havoc on NIH and other national priorities.
    With a non-defense cap that increases by $583 million this 
year, it is mathematically impossible to fully replace the 
remaining NIH sequester and provide just an inflationary 
increase to NIH without forcing additional cuts to education, 
and job training, and other priorities.
    By not replacing the sequester this year, we are foregoing 
$56 billion that could be invested in programs to grow our 
economy, programs like NIH. The President proposed a fully 
offset opportunity growth and security initiative that 
represents the $56 billion in lost--that was lost to sequester. 
That initiative would allow for investing an additional $900 
million in NIH, enough to bring NIH back to the pre-sequester 
level and then provide a small increase. That is what we are 
losing by clinging to this devastating policy of sequester. 
Make no mistake: Keeping the sequester in place will mean a 
steady, destructive erosion in our NIH investment. It is no 
longer a question of politics; it is just a question of math.
    So I look forward to the discussion today about the 
exciting work that NIH is doing in the face of these budget 
problems, and in the hopes that we can all work together to 
support this vital institution, and to maintain America's 
leadership in our biomedical sciences. With that, I will yield 
to Senator Moran for his opening statement.


                    statement of senator jerry moran


    Senator Moran. Mr. Chairman, thank you. I look forward to 
continuing to work with you during the remainder of your term 
as chairman of this subcommittee along with Senator Shelby, the 
ranking member, and Chairwoman Mikulski to see that we 
accomplish some of the goals that you outlined in your 
statement.
    And I do appreciate Dr. Collins and his colleagues being 
with us today to discuss the National Institutes of Health. In 
my view, NIH represents hope for millions of patients suffering 
from conditions from Alzheimer's disease to cancer. NIH-funded 
research has raised life expectancy, improved the quality of 
life, and is an economic engine helping to sustain America's 
competitiveness.
    Over the past year, cutting-edge NIH-supported research 
discovered a blood test to predict if a healthy person will 
develop dementia or Alzheimer's disease, uncovered a set of 
rare mutations to a gene that provides protection against type 
2 diabetes, and used targeted immunotherapy to induce remission 
in leukemia. What wonderful developments. A continued 
commitment to NIH is essential to address our Nation's growing 
health concerns, spur medical innovation, sustain American 
competitiveness, and reduce healthcare costs.
    I think NIH is at a critical juncture. We have spent years 
focusing on doubling the NIH budget, and now a decade later the 
NIH budget is falling victim to an Administration's budget that 
does not prioritize biomedical research. The fiscal year 2015 
budget touts an increase of $200 million, or 0.7 percent, 
seven-tenths of a percent. However, with the use of, really, a 
budget gimmick, the increase is all but eliminated with the 
President's proposal to increase the evaluation set-aside. 
Under the President's proposal, $142 million of the $200 
million increase would be transferred to other programs within 
the Department of Health and Human Services, leaving NIH with 
only a $58 million increase.
    Without a consistent commitment to funding our premiere 
medical research agency, the future of biomedical research in 
the United States is in jeopardy. Grant success rates are at an 
all-time low. The average age of a first-time R01 grantee is 42 
years old, up from 38 years old in 1980. I looked out across 
the list of the panel of witnesses and discovered that you all 
remain very young, so perhaps that is defeating the point I am 
trying to make. But our researchers are becoming older as we 
continue this process. In fact, our principal investigators who 
are 65 or older receive more than twice as many R01 grants than 
those 36 and under. Young scientists, which we desperately 
need, will be discouraged by these statistics, and many have 
fled research fields or left for opportunities in other 
countries, putting our Nation at a serious risk for losing our 
global competitiveness in the biomedical research field and 
reducing the chances that we find cures and treatments.
    Dr. Collins has consistently raised this concern about what 
he calls ``deep long-term damage'' to biomedical research, and 
we should all pay attention to his warnings. We cannot let 
these research opportunities slip away. We cannot lose the 
brilliant scientists, the scientific minds that will make 
future ground-breaking discoveries in biomedical research to 
alternative careers or other countries. And we must not 
squander the scientific capacity that we have developed.
    I believe funding decisions represent more than just 
dollars. They reflect our Nation's priorities. And this 
Congress faces unprecedented challenges to reduce Government 
spending. Now is the time to reevaluate our funding priorities 
and invest after evaluating those priorities in biomedical 
research. This is the time of promise in research, and the 
United States should be at the forefront in this area. To do 
so, we must commit to pay for the research. We must accomplish 
this. And I thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Moran. Well, again, Dr. 
Collins and colleagues, welcome again to our subcommittee. I 
got your statement. I read it. It will be a part of the record 
in its entirety. And, Dr. Collins, we will recognize you. Just 
proceed as you so desire for 10 minutes or so, or whatever it 
takes you to get it done. Welcome back, Dr. Collins.


              summary statement of dr. francis s. collins


    Dr. Collins. Well, thank you, and good morning, Chairman 
Harkin, Ranking Member Moran, and members of the subcommittee. 
Let me introduce the folks at the table who are here with me: 
Over to your right, my left, Dr. Harold Varmus, the Director of 
the National Cancer Institute (NCI), formerly the director of 
the NIH; next to him, Dr. Gary Gibbons, Director of the 
National Heart, Lung, and Blood Institute; and immediately to 
my left, Dr. Christopher Austin, Director of the new National 
Center for Advancing Translational Sciences, NCATS; to my 
right, Dr. Story Landis, the Director of the National Institute 
of Neurological Disorders and Stroke; and finally as already 
mentioned, Dr. Anthony Fauci, Director of the National 
Institute of Allergy and Infectious Diseases. And they are here 
to answer your questions, as am I.
    Well, it is a great honor for us to be here to appear 
before you and present the Administration's fiscal year 2015 
budget request, and to provide an overview of our Agency's 
critical role in enhancing the Nation's health through 
scientific discovery. But before I begin today, I would be 
remiss if I did not take a moment to thank you, Mr. Chairman, 
for your extraordinary leadership on this subcommittee over 
these 25 years. You have been a remarkable--I would say even 
historic--advocate for biomedical research and for the NIH. We 
are all very grateful for your service, and will truly miss you 
on this subcommittee in the years to come.
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                 national institutes of health mission


    Dr. Collins. NIH has been advancing our understanding of 
health and disease for more than a century. Scientific and 
technological breakthroughs generated by NIH-supported research 
are behind many of the gains that you can see in this image of 
how our country has enjoyed gains in longevity and in health. 
For example, over the last 60 years, deaths from heart disease 
have fallen by more than 70 percent. Meanwhile, cancer death 
rates, as you have already cited, have been dropping about 1 
percent annually for the last 15 years, life expectancy gains 
that have saved our Nation trillions of dollars. Likewise, HIV/
AIDS treatments have greatly extended lives, and prevention 
strategies are enabling us to envision the first AIDS-free 
generation since this virus emerged more than 30 years ago.
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    Dr. Collins. But none of these advances could have happened 
without the strong support of the Administration and the U.S. 
Congress, and specifically of this subcommittee. This 
subcommittee came together in a bipartisan way, and I want to 
thank you for that, to make it possible in the fiscal year 2014 
omnibus appropriation to turn a corner.


                           budget challenges


    To be honest, the previous year was quite challenging for 
us. Sequestration applied damaging cuts to ground-breaking 
medical research and affected the morale of the scientific 
community. That impact was further exacerbated by the 
Government shutdown, which forced me to send 12,000 scientists 
home for 16 long days, and required us to turn patients away 
from the NIH Clinical Center.
    With the fiscal year 2014 omnibus, we are optimistic that a 
corner has been turned after a difficult decade during which 
NIH has lost more than 20 percent of its purchasing power for 
medical research, 20 percent down from where we were in 2003. 
The Administration now proposes a fiscal year 2015 budget 
request that is $211 million, or .7 percent, above the fiscal 
year 2014 level. This budget request reflects the President's 
and the Secretary's commitment to improving the health of the 
Nation and to maintaining our leadership in the life sciences 
while remaining within the constraints of the Murray-Ryan 
budget envelope. It allocates resources to areas with the most 
extraordinary promise for medical research, while maintaining 
the flexibility to pursue unexpected scientific opportunities, 
and to address unforeseen public health needs.
    Within the Administration's fiscal year 2015 budget, NIH 
will increase our primary funding mechanism for investigator-
initiated research, the research project grants, or RPGs. And 
this is a critical priority. In fiscal year 2013, our grant 
success rate, as you can see in this graph, reached an all-time 
low of 16.8 percent, a number that desperately needs to rise 
again.
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    Dr. Collins. By careful stewardship of resources, we expect 
to support 9,326 new and competing RPGs next fiscal year, which 
will be an increase of 329 over fiscal year 2014 levels, 
although the total number of grants we support will remain 
approximately the same.
    But now, let me turn to some of the exciting scientific 
opportunities that NIH is pursuing today.
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                     future of biomedical research


    Dr. Collins. I can assure you the future of biomedical 
research has never been brighter. Basic science, for which the 
Federal Government serves as the main source of support in the 
U.S., had led the way. Advances in genomics, proteomics, stem 
cells, imagine, the microbiome, and other technologies have led 
to phenomenal advances in our understanding of how life works, 
and also the discovery of more than a thousand new risk factors 
for disease.
    NIH will continue to spend a little more than half of our 
budget on these basic science advances. But as you know, we are 
also deeply committed to catalyzing the translation of these 
discoveries into clinical advances. And this can be quite 
challenging to the dismay of researchers, drug companies, and 
especially patients. We face a situation today where the vast 
majority of drugs entering the development pipeline fall by the 
wayside.
    The most distressing failures, as you see here, occur when 
a drug is found to be ineffective in the later stages of 
development, in phase two or phase three clinical trials, after 
years of work and millions of dollars have already been spent.
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                   accelerating medicines partnership


    Dr. Collins. A major reason for such failures is that 
scientists often have not had enough information to choose the 
right biological targets, and if a drug is aimed at the wrong 
target, it will not be effective against the disease it was 
intended to treat, and a failure will occur.
    So to this end, we were particularly thrilled to announce 
the launch of the Accelerating Medicines Partnership, AMP, just 
6 weeks ago.
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    Dr. Collins. This pre-competitive partnership, which will 
share all data openly, will initially focus on three disease 
areas that are ripe for drug discovery: Alzheimer's disease, 
type 2 diabetes, and the autoimmune disorders lupus and 
rheumatoid arthritis.
    Besides NIH, the partners in AMP include the FDA and 10 
biopharmaceutical firms, listed here, and a number of non-
profits, including patient advocacy groups.
    [The graphic follows:]

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                         universal flu vaccine


    Dr. Collins. This unprecedented public/private 
collaboration will use cutting-edge scientific approaches to 
sift through a long list of potential therapeutic targets and 
choose those most likely to lead to success, with the cost 
being shared evenly by NIH and industry.
    But we are not stopping there. Influenza is another area 
where we are poised for rapid progress. In fact, NIH-funded 
scientists are well on their way to developing a universal 
vaccine. The outside of the flu virus, shown here, is coated 
with tiny mushroom-shaped proteins, and each of these proteins 
has a head and a stem.
    [The graphic follows:]

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    Dr. Collins. Current vaccines target the head of that 
mushroom, but this mutates over time. Here you can see in 
yellow the changes that occurred in three different flu 
viruses.
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    Dr. Collins. These changes, primarily in the head, are 
happening all the time. To keep up, a new vaccine must be 
produced every year.
    On the other hand, you can see here the stem of the viral 
protein remains almost entirely unaltered over time. A 
universal flu vaccine that targets the relatively stable stem 
would not only eliminate the need for an annual flu shot, but 
would also provide protection against outbreaks like the H5N1 
and H7N9 events in Southeast Asia that are causing considerable 
worldwide concern right now.


                            brain initiative


    Another major challenge is exploring what has been called 
the most complex structure in the known universe, the human 
brain. As you know, NIH is leading the new Brain Research 
through Advancing Innovative Neurotechnologies, B-R-A-I-N, 
BRAIN Initiative, and we are grateful for your support.
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    Dr. Collins. This initiative will provide a foundational 
platform for major advances in Alzheimer's disease, autism, 
schizophrenia, traumatic brain injury, epilepsy, and many other 
brain disorders.
    But a final area of scientific opportunity that I want to 
highlight today involves one of our Nation's biggest and most 
feared killers, cancer. Until recently, our weapons for 
attacking cancer have been surgery, radiation, and 
chemotherapy, all of which can be effective, but carry risks. 
Recent advances have given us insights into the intricate 
workings of the cancer cell, and a whole new generation of 
targeted therapeutics is emerging, ushering in an era of 
individualized precision medicine.
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                    opportunities in cancer research


    Dr. Collins. This image on the left shows a dramatic 
example of just how effective such targeted therapies can be 
because on the left is a scan of a melanoma patient who carries 
a mutation and a gene that codes a protein called B-Raf. Now, 
B-Raf is implicated when mutated in the development of cancer. 
The hot spots that you see all over this individual's body 
indicate dividing cancer cells that have spread throughout. 
After treatment with a new drug targeted to block the effects 
of mutant RAF, those hot spots almost vanish. The promise of 
targeted therapy is apparent.
    But now, there is a new powerful weapon in the arsenal, 
cancer immunotherapy, a revolutionary new approach that Science 
magazine named its 2013 breakthrough of the year.
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    Dr. Collins. This involves harnessing the body's own immune 
system to fight this dreaded disease. In one of those new 
approaches, certain types of immune cells called T-cells--you 
can see them here--are collected from cancer patients and 
engineered to produce special proteins on their surface. When 
these engineered T-cells are infused back into patients, they 
have the power to seek and destroy cancer cells.
    And in this video, you can see one of those modified T-
cells doing just that, actually obliterating the cancer cell.
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    Dr. Collins. Knowing how to turn T-cells into little Ninja 
warriors required big investments in basic biomedical research 
over more than a decade, but the consequences are starting to 
be amazing.
    I would like to share this story, in closing, of Emily 
Whitehead.
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    Dr. Collins. Nearly 2 years ago, this brave little girl 
became the first pediatric patient to be treated with a new 
kind of cancer immunotherapy. Emily was suffering from acute 
lymphoblastic leukemia, a disease that, as was pointed out by 
Senator Moran, now we cure 90 percent of the time with 
chemotherapy. But distressingly, Emily was in the 10 percent 
where that fails.
    Her parents decided to enroll her in a pioneering cancer 
immunotherapy trial at the Children's Hospital of Philadelphia. 
Emily's T-cells were collected from her blood and re-engineered 
in the lab to recognize a protein found only on the surface of 
her leukemia cells. Those T-cells were then infused back into 
Emily's blood where they circulated throughout her body on a 
mission to seek and destroy leukemia. Just 28 days after 
treatment, she was cancer free, and she remains so to this day.
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    Dr. Collins. Here is Emily today, a happy, healthy third 
grader who is looking forward to celebrating her ninth birthday 
next month. As her mom, Kerry, puts it, ``If you didn't know 
what happened to her and you saw her now, you would have no 
idea what she has been through.'' A wonderful story of success.


                          prepared statements


    And, Senators, I believe there are a great many more Emilys 
on the horizon. Our Nation has never witnessed a time of 
greater promise for advances in medicine. With your support, we 
can realize our vision of accelerating discovery across the 
vast landscape of biomedical research. From basic scientific 
inquiry to human clinical trials, the National Institutes of 
Hope is ready to move forward.
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    Dr. Collins. Thank you, Mr. Chairman, for your support of 
NIH. My colleagues and I welcome your questions.
    [The statements follows:]
         Prepared Statement of Francis S. Collins, M.D., Ph.D.
    Good morning, Mr. Chairman and distinguished members of the 
subcommittee. I am Francis S. Collins, M.D., Ph.D., Director of the 
National Institutes of Health (NIH). It is an honor to appear before 
you today to present the Administration's fiscal year 2015 budget 
request for the NIH and provide an overview of our critical role in 
enhancing our Nation's health through scientific discovery.
    As the Nation's biomedical research agency, 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 
this mission.
    Before I discuss the tremendous strides we have made and the 
exciting scientific opportunities on the horizon, I want to thank you, 
Mr. Chairman, and Ranking Member Moran, as well as your colleagues, for 
the recent fiscal year 2014 Omnibus Appropriation bill. The 
subcommittee came together in a bipartisan way to increase funding for 
NIH and we are truly grateful for your action. The past year has been 
challenging for us: The sequester reduced funding for groundbreaking 
medical research and affected the morale of the scientific community. 
This impact was further exacerbated by the shutdown.
    There is much good news to report about the science that we 
support. NIH has been advancing our understanding of health and disease 
for more than a century; scientific and technological breakthroughs 
generated by NIH-supported research are behind much of the gains our 
country has enjoyed in health and longevity. For example, deaths from 
heart disease have been reduced by more than 70 percent from 1950 to 
2008. Cancer death rates have been dropping about 1 percent annually 
for the past 15 years--life expectancy gains that save the Nation 
billions of dollars. HIV/AIDS treatment and prevention now enable us to 
envision the first AIDS-free generation since this virus emerged more 
than 30 years ago. NIH research also has given us vaccines to protect 
against an array of life-threatening diseases, including 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 significantly better chance of living a long and 
healthy life.
    These statistics tell you how far we have come--but our aim is to 
go even further, faster. To this end, the Administration's fiscal year 
2015 budget request for the NIH is $30.362 billion, $211 million, or 
0.7 percent, above the fiscal year 2014 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 2015 budget request will enhance NIH's ability to 
support cutting-edge research and training of the scientific workforce. 
Within the Administration's fiscal year 2015 budget, we will continue 
to increase Research Project Grants (RPGs), NIH's funding mechanism for 
investigator-initiated research. NIH expects to support 9,326 new and 
competing RPGs in fiscal year 2015, an increase of 329 over fiscal year 
2014 levels. For fiscal year 2015, NIH anticipates funding a total of 
34,197 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.
    While we are very grateful for any budget increase, the fully paid 
$56 billion Opportunity, Growth, and Security Initiative (OGSI), a 
program included in the President's budget, would provide an additional 
$970 million investment in NIH programs that would allow NIH to fund or 
expand a host of other cutting-edge initiatives, speeding the 
development of vaccines and cures, and restoring sequestration cuts to 
the number of research project grants.
    Let me describe a few of the many areas in which NIH-supported 
research is opening up extraordinary opportunities to improve the 
health of the American public.
    A major program that began this year is the Brain Research through 
Advancing Innovative Neurotechnologies (BRAIN) Initiative, for which 
thanks are due to this subcommittee for its fiscal year 2014 support. 
NIH is a major player in this pioneering multiagency venture that will 
enable the creation of new tools capable of examining the activity of 
billions 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 decode sensory experience and, potentially, 
even memory, emotion, and thought. Successful pursuit of the BRAIN 
Initiative will revolutionize neuroscience, providing a foundational 
platform for major advances in Alzheimer's disease, autism, 
schizophrenia, epilepsy, traumatic brain injury, and many other brain 
disorders.
    As technology allows us to tackle mind-boggling tasks like 
recording the activity of billions of nerve cells in the brain or 
determining the DNA sequence of tens of thousands of human genomes, 
researchers are generating enormous quantities of data at an 
unprecedented pace. The challenge posed by this revolution is how to 
store, retrieve, integrate, and analyze this mountain of complex data--
and transform it into knowledge that can improve human health. To 
address this challenge that affects virtually all areas of biomedical 
research, we have just launched the Big Data to Knowledge (BD2K) 
initiative. The goals of BD2K are to develop and disseminate new 
analytical methods and software, enhance training of data scientists, 
and facilitate broad use and sharing of complex biomedical datasets. 
With sustained investment and effort, we will overcome the challenges 
associated with Big Data to accelerate real-world applications of basic 
science discoveries.
    We are also excited about another area of intense interest: the 
development of therapeutics. Recent advances in genomics, proteomics, 
imaging, and other technologies have led to the recent discovery of 
more than a thousand risk factors for disease--biological insights that 
ought to hold promise as targets for drugs. But drug development is a 
terribly difficult and failure-prone business. To the dismay of 
researchers, drug companies, and patients, the vast majority of drugs 
entering the development pipeline fall by the wayside. The most 
distressing failures occur when a drug is found to be ineffective in 
the later stages of development--in Phase II or Phase III clinical 
studies--after years of work and millions of dollars have already been 
spent. A major reason for such failures is that scientists often have 
not had enough information to choose the right biological targets. If a 
drug is aimed at the wrong target, it won't work against the disease it 
was intended to treat.
    With that challenge in mind, we were thrilled last month to launch 
the Accelerating Medicines Partnership (AMP). This unprecedented 
public-private effort will use cutting-edge scientific approaches to 
sift through a very long list of potential therapeutic targets, and 
choose those most likely to lead to success. Besides NIH, the AMP 
partners include the FDA, 10 biopharmaceutical firms and a number of 
nonprofits, including patient advocacy groups. This precompetitive 
partnership, which will share all data openly, will initially focus on 
three disease areas that are ripe for discovery: Alzheimer's disease, 
type 2 diabetes, and the autoimmune disorders, lupus and rheumatoid 
arthritis. Through this team effort, we believe we can reach our shared 
goals of treating and curing disease faster.
    Preventing disease is another top priority, and influenza is one 
area of prevention in which we are poised for rapid progress. 
Currently, to provide protection against the rapidly evolving influenza 
virus, a new vaccine must be produced each year and we all need to get 
an annual flu shot. Also, despite best efforts, the vaccine isn't 
always ideal. In an average year, the flu claims up to 49,000 American 
lives and costs the U.S. economy about $87 billion. But it does not 
have to be that way. NIH-funded researchers are now working on a 
universal flu vaccine--designed to protect people against virtually all 
strains of the flu for extended periods of time and, thus, potentially 
reduce the need for annual flu shots. Of critical importance, such a 
vaccine could also protect against a future global flu pandemic.
    While we are several years away from having a universal flu vaccine 
available to the public, our researchers have already demonstrated 
proof of concept and are testing a number of approaches, including two-
stage ``prime boost'' vaccines and ferritin nanoparticles. Clearly, the 
prospect of a universal flu vaccine is not science fiction. Early 
clinical studies are already underway. With sustained investment, the 
United States may be a few years away from realizing its potential to 
benefit our health and our economy.
    As impressive as a universal flu vaccine would be, it is not the 
only trick we are teaching our immune systems. We are also aiming to 
harness the body's own immune system to fight cancer. Until recently, 
our weapons for attacking cancer have been largely limited to surgery, 
radiation, and chemotherapy--treatments that carry risks and cause 
adverse side effects. Now, after years of intense basic and 
translational research, we have an exciting new possibility: Cancer 
immunotherapy.
    Researchers have long been puzzled by the uncanny ability of cancer 
cells to evade the immune response. What stops the body from waging its 
own ``war on cancer?'' As it turns out, our bodies have built-in 
checkpoints to prevent our immune systems from going into overdrive and 
killing healthy cells. Now, NIH-funded researchers have discovered a 
way to genetically modify certain white blood cells called T-cells--the 
soldiers of the immune system--to attack tumor cells. In this new 
approach, T-cells are collected from cancer patients and engineered in 
the lab to produce special proteins on their surface, called chimeric 
antigen receptors (CARs). When the modified cells are infused back into 
patients, they multiply and, with guidance from their newly engineered 
receptors, seek and destroy tumor cells. Promising results in patients 
with leukemia prompted Science magazine to name this its 2013 
Breakthrough of the Year.
    Today, I have provided a very brief overview of NIH's past 
successes and continuing commitment to basic, translational, and 
clinical research. Our Nation has never witnessed a time of greater 
promise for advances in medicine. With your support, we can anticipate 
a future of accelerating discovery across NIH's broad research 
landscape, from fundamental scientific inquiry to human clinical 
trials. The ``National Institutes of Hope'' is ready to move forward.
    This concludes my testimony, Mr. Chairman. I look forward to your 
questions.
                                 ______
                                 
              Prepared Statement of Anthony S. Fauci, M.D.
    Mr. Chairman and Members of the Committee: I am pleased to discuss 
current and future plans for biomedical research at the National 
Institute of Allergy and Infectious Diseases (NIAID) of the National 
Institutes of Health (NIH). The President's fiscal year 2015 NIAID 
budget request of $4,423,357,000 billion is approximately $31 million 
more than the fiscal year 2014 funding level ($4,392,670,000).
    NIAID conducts, supports, and translates basic and clinical 
research into the development of diagnostics, therapeutics, and 
vaccines to detect, treat, and prevent infectious and immune-mediated 
diseases. NIAID has a dual mandate that balances research addressing 
current biomedical challenges with the capacity to rapidly respond to 
new threats from emerging and re-emerging infectious diseases and 
bioterrorism.
                      infectious diseases research
    HIV/AIDS.--NIAID is leading transformational progress in basic and 
clinical research on HIV/AIDS. The decades-long NIAID investment in 
HIV/AIDS research has made the goal of an AIDS-free generation a 
possibility with sustained effort. NIAID continues to improve and 
refine HIV prevention and treatment tools, including antiretroviral 
therapies to effectively manage disease and reduce HIV transmission, 
and pre-exposure prophylaxis to protect against HIV. NIAID also is 
advancing research toward the development of an effective HIV vaccine 
to complement existing prevention strategies. HIV vaccine development 
will be informed by NIAID efforts to identify immunological markers in 
the subset of people protected against HIV infection in the RV144 
trial, the first HIV vaccine trial to show modest efficacy. The NIAID 
Vaccine Research Center together with several NIAID grantees are making 
rapid progress on ways to generate broadly neutralizing antibodies to 
protect against multiple strains of HIV, research that may translate to 
vaccines and therapeutics of global public health significance.
    Years of NIAID-supported research on HIV pathogenesis and the role 
of HIV reservoirs have suggested the feasibility of curing some HIV-
infected individuals. NIAID will investigate promising reports of a 
handful of infants who were born HIV-positive but now test negative for 
the virus following aggressive antiretroviral treatment initiated 
shortly after birth by supporting a clinical trial to determine if this 
strategy is safe and effective for other infants. NIAID also will play 
a major role in implementing the President's $100 million HIV/AIDS cure 
research initiative. As part of this effort, NIAID will support 
additional research on HIV latency and persistence. Understanding these 
processes may reveal new strategies toward a cure.
    NIAID recently restructured its HIV/AIDS Clinical Trials Networks 
to capitalize on the growing body of promising HIV research findings 
and to better address current research questions. The Networks will 
focus on improved ways to prevent and treat HIV, tuberculosis and 
hepatitis C co-infections, and on research toward development of a 
vaccine, microbicides, and a cure.
    Tuberculosis.--Tuberculosis (TB) remains a significant cause of 
illness and death throughout the world, especially among those also 
infected with HIV. NIAID recently launched a genome sequencing project 
that will examine the genetic diversity of TB bacteria and patterns of 
drug resistance to understand TB pathogenesis and to identify new drug 
targets and molecular mechanisms of resistance. This research will be 
particularly important to address the emergence of multi- and 
extensively drug-resistant TB. NIAID-supported scientists also are 
working to modify the existing antibiotic spectinomycin to bypass 
mechanisms of resistance to this drug. These efforts have shown promise 
in TB animal models.
    Malaria.--NIAID continues to progress toward its goal to control, 
eliminate, and ultimately eradicate malaria worldwide. The development 
of vaccines is a critical part of this endeavor. NIAID researchers and 
grantees recently completed an early-stage clinical trial that showed a 
novel vaccine composed of weakened malaria sporozoites was safe and 
protected against malaria. NIAID has developed two new tests to rapidly 
and inexpensively detect resistance to artemisinin, a first-line 
antimalarial drug. NIAID also is exploring innovative methods to 
control the spread of malaria. For example, NIAID-funded researchers 
have established a bacterial infection that passes from female 
mosquitoes to their offspring and kills malaria parasites within the 
mosquitoes before they can infect humans.
    Other Infectious Diseases of Domestic and Global Health 
Importance.--NIAID is committed to research on infectious diseases 
affecting global health. Influenza is among the most important 
infectious diseases of domestic and global concern. NIAID research 
addresses the challenge of seasonal influenza and prepares for the 
threat of an emerging pandemic. NIAID is developing and evaluating 
vaccines against the avian influenza strains H5N1 and H7N9 to deploy if 
needed to prevent further spread among humans. NIAID also is examining 
these vaccines paired with adjuvants--components that enhance the 
immune response--to provide the greatest protection with the smallest 
dose possible. NIAID investigators and grantees are making significant 
progress toward the development of a universal influenza vaccine that 
could generate durable protection over a period of years against a wide 
range of seasonal and pandemic influenza strains. Studies conducted by 
NIAID scientists at the NIAID Special Clinical Studies Unit in the NIH 
Clinical Center are providing important clues into the susceptibility 
and immune response of patients to influenza infection. Future studies 
will examine the effectiveness of new vaccines and therapeutics.
    Respiratory syncytial virus (RSV) is a serious respiratory 
infection primarily of young children that causes significant illness 
and hospitalizations in the U.S. and thousands of deaths worldwide. 
There is no vaccine to protect infants and children against RSV. 
Researchers at the NIAID Vaccine Research Center recently determined 
the structure of a key RSV protein bound to a broadly neutralizing 
human RSV antibody and used it to design an experimental RSV vaccine 
that is effective in animal models. NIAID has advanced this 
groundbreaking RSV vaccine into early-stage clinical trials in humans. 
Science magazine highlighted this discovery among the top 10 scientific 
breakthroughs in 2013.
    Hepatitis C virus (HCV) is a significant cause of chronic liver 
disease and cancer, and often co-infects people with HIV. Traditional 
HCV therapies frequently have severe side effects and may not be 
successful in many patients. NIAID and NIH Clinical Center 
investigators recently led a Phase II trial of a new HCV drug, 
sofosbuvir. The trial demonstrated that sofosbuvir, combined with the 
antiviral drug ribavirin, was highly effective and well tolerated even 
in patients predicted to have poor outcomes with traditional HCV 
treatments. Sofosbuvir and similar therapies for the treatment of HCV 
have recently been approved, potentially revolutionizing treatment 
outcomes.
    Antimicrobial resistance is a significant public health challenge 
and an NIAID priority. NIAID recently reassessed research needs for 
this important issue and established a Leadership Group to design, 
implement, and manage the clinical research agenda for a new 
antibacterial resistance research network. NIAID provides resources to 
lower the investment risk for industry, academia, and non-profit 
organizations to facilitate a robust pipeline of diagnostics, vaccines, 
and therapeutics for resistant microbes.
          research on immunology and immune-mediated disorders
    NIAID's commitment to research on basic and clinical immunology 
continues to foster important insights that ultimately will help to 
better treat and prevent immune-mediated disorders, including food 
allergy. NIAID-funded investigators recently demonstrated that female 
sex hormones affect the gut microbiome and promote development of 
autoimmunity in an animal model, providing clues into why women are 
more likely to be affected by autoimmune diseases. NIAID-supported 
researchers have made progress in understanding how exposure to certain 
microbes in early life, especially those found in homes with dogs, may 
protect against the development of asthma and other allergies. NIAID 
grantees also developed two urine tests to diagnose and predict 
rejection of a transplanted kidney. These simple tests could one day 
replace the invasive procedure currently used to detect organ rejection 
and particularly would benefit African Americans, who are 
disproportionately affected by organ transplant rejection.
                               conclusion
    For more than 60 years, basic and clinical research conducted and 
supported by NIAID on infectious and immune-mediated diseases has 
spurred the development of vaccines, therapeutics, and diagnostics to 
improve the health of millions around the world. NIAID will continue to 
perform the basic, clinical, and translational research critical to 
advancing the health of our Nation and the world.
                                 ______
                                 
              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 2015 NCI 
budget of $4,930,715,000 includes an increase of $7,944,000, or 0.2 
percent, compared to the fiscal year 2014 level of $4,922,771,000.
                  overview of nci research priorities
    This is an era of remarkable opportunity in cancer research. Armed 
with broad knowledge about how various cancers arise and with powerful 
new research tools, the NCI is well equipped to accelerate progress 
towards preventing, diagnosing, and treating cancer more effectively. 
This era of opportunity is due in significant part to the 
subcommittee's consistent support for biomedical research at NCI and 
NIH.
    The resources that you provide allow NCI to address an ambitious 
challenge: reducing the incidence, morbidity, and mortality for all of 
the many types of cancer, with tangible benefits for all Americans. The 
fiscal year 2015 budget will allow the NCI to build on the tremendous 
progress in many areas of cancer research, with the aim of improving 
outcomes for patients with all types of cancer.
    I will summarize some recent accomplishments and highlight new 
opportunities in five areas of NCI-supported research--genomics, cancer 
immunology, targeted therapeutics, bioinformatics, and prevention--to 
illustrate the breadth and pace of NCI's progress.
    The Cancer Genomics research that NCI supports has dramatically 
altered our understanding of how cancer develops, identified the 
molecular signatures that can be used to diagnose and categorize cancer 
more precisely, and provided new targets for therapeutic intervention. 
For example, two major initiatives--TCGA (The Cancer Genome Atlas) and 
TARGET (Therapeutically Applicable Research to Generate Effective 
Treatments)--have addressed nearly twenty common adult cancers and 
several less common cancers that occur in adults and children, 
revealing both tissue-specific patterns of genetic changes and changes 
that are common to several types of cancers. TCGA is a joint initiative 
of the NCI and the Human Genome Research Institute. During the past 
year, TCGA published comprehensive characterizations of acute myeloid 
leukemia, endometrial cancer, and clear cell renal carcinoma, among 
others. While every cancer is distinct genetically, many changes in the 
genome are shared among a wide array of cancer types, and each type of 
cancer has distinct patterns that often reflect exposure to 
carcinogenic agents, such as tobacco smoke and ultraviolet radiation. 
As these massive surveys come to conclusion, the NCI's Center for 
Cancer Genomics is leading efforts to make full use of the TCGA 
results, including the best ways to incorporate genomic findings into 
the design of clinical trials.
    Some of the surprising findings from the TCGA and TARGET projects--
such as the involvement of genes that govern the chemistry of 
chromosomal proteins, that influence cell metabolism, and that guide 
the processing of RNAs and proteins--are influencing the study of 
cancer biology throughout the NCI's programs. TCGA and TARGET will 
certainly enlarge our understanding of carcinogenesis and will likely 
open new frontiers for preventing, diagnosing, and treating cancers.
    Cancer immunology is a rapidly advancing field that, in just the 
past few years, has dramatically altered our understanding of host 
defenses in response to cancers. It has also produced new and well-
validated methods for treating cancer using antibodies that attach to 
proteins on cancer cell surfaces and using methods that modulate the 
complex behavior of the immune system to attack cancer cells.
    For several years, monoclonal antibodies against cancer cell 
proteins have been used to treat blood cancers, such as certain 
lymphomas and leukemias, and subsets of several types of solid tumors, 
such as breast and colorectal cancer. More recently, immunotoxins have 
been created by genetic engineering to fuse antibodies with parts of 
bacterial toxins to selectively kill cancer cells. For example, such 
immunotoxins developed in the NCI intramural program have induced 
remissions in late stage cases of mesothelioma, ovarian cancer, triple-
negative breast cancer, drug-resistant hairy cell leukemia, and 
childhood acute lymphoblastic leukemia.
    There is also great optimism within the science community about 
modulating the immune system by introducing novel antigen receptors 
into cancer-killing T cells and especially by infusing antibodies that 
interfere with a system that impedes the immune response to cancer 
cells. These ``immune-modulating'' antibodies have recently received 
FDA approval, and other antibodies that bond other immune cell 
regulators may soon follow. In 2011, FDA approved a monoclonal 
antibody, called ipilimumab, to treat advanced melanoma. Some patients 
with metastatic melanoma being treated with ipilimumab are still alive 
several years after completing treatment. In 2013, another promising 
antibody to treat melanoma--lambrolizumab--received ``breakthrough'' 
designation by the FDA, helping expedite its development and further 
use in clinical trials, with the possibility of an expedited FDA 
review. In recognition of these and other recent achievements in the 
field of immunology, and the promise of further developments, ``cancer 
immunotherapy'' was named this year's Breakthrough of the Year by 
Science magazine.
    Targeted therapies, based on the use of drugs that inhibit specific 
proteins implicated in the behavior of cancer cells, are now being 
developed and tested for their effects in patients with many types of 
cancer. Over the past decade, FDA has approved several drugs that rely 
on this therapeutic approach to treat cancers of blood cells, lung 
cancer, melanoma, and other cancers, and many more are in development. 
This activity has accelerated because of discoveries in genomics, cell 
signaling pathways, chemistry, and structural biology, and with the 
identification of new ways to inhibit proteins that are required for 
the integrity of cancer cells.
    Mutant RAS proteins are perhaps the most prominent potential 
targets for new therapies that the academic and commercial research 
sectors have thus far failed to target with inhibitory drugs. The 
importance of the RAS gene family in cancer has been clear for over 30 
years; one family member, K-RAS, is mutated in more than 90 percent of 
pancreatic adenocarcinomas, about 40 percent of colorectal cancers, and 
about 25 percent of lung adenocarcinomas. For this reason, the NCI 
recently launched the RAS Project, a large-scale collaboration between 
investigators at the NCI's Frederick National Laboratory for Cancer 
Research and those in NCI's intramural and extramural communities. The 
RAS Project is motivated in part by new developments in the study of 
RAS proteins, including new information about their structural 
properties, binding of mutant RAS proteins to mutant-specific 
inhibitors, interactions with other cellular proteins required for 
function, and new tests for genes required to allow RAS mutants to 
exert their effects.
    Still, while pursuing a path that leads to ``precision medicine,'' 
the NCI must also maintain its capacity to test new ways to deploy the 
currently dominant means of therapy. For instance, a recent study of 
patients with metastatic prostate cancer showed markedly increased 
survival in men who received chemotherapy when starting anti-androgenic 
hormone therapy, a result that is likely to change clinical practice 
for a cancer that continues to kill about 30,000 American men annually.
    Drug resistance commonly emerges in cancers being treated with 
either traditional chemotherapies or novel targeted therapies, allowing 
disease to progress. Over the past decade, NCI-supported studies have 
revealed several mechanisms by which resistance occurs, including 
additional mutations affecting the target molecules, mutations in 
related genes, and changes in gene expression. In some cases, 
especially chronic myeloid leukemias, drugs that overcome resistance 
have been identified, developed and FDA-approved. But in other 
situations, resistance to targeted drugs remains a major impediment to 
success, and the NCI is making major investments to study this problem.
    Bioinformatics, the management of enormous sets of molecular and 
clinical data is a critical component of NCI's toolkit to study cancer 
in all of its manifestations. In work that ranges from cancer genomics, 
to cell signaling, and to clinical trials, the proper collection, 
analysis, storage, retrieval, and distribution of ``big data'' are 
critical elements of the Institute's charge. The NCI's Center for 
Bioinformatics and Information Technology (CBIIT) is addressing these 
responsibilities, in conjunction with NCI divisions. Part of the 
current effort requires the costly development of ``cloud computing'' 
to work with the vast (petabyte) amounts of genomic data generated by 
TCGA, TARGET, and other projects, and to assemble and ultimately 
integrate clinical data with genomic data in manageable forms to 
promote further discovery and improve cancer care.
    Prevention of cancer remains NCI's most desired goal. While 
complete avoidance of cancer may be impossible, since cancers often 
arise through spontaneous mutations, the control of tobacco use, 
vaccination against cancer-causing viruses (human hepatitis B virus and 
human papillomaviruses), sunlight avoidance, and regulation of dietary 
and carcinogenic substances (such as asbestos) have already reduced the 
incidence and the mortality rates of many cancers. For instance, 
between 2001 and 2010, largely due to the earlier reductions in tobacco 
use, there was a 25 percent decrease in male death rates and an 8 
percent decrease in female death rates due to lung cancer, the major 
cause of death from cancer in the United States. Likewise, vaccination 
with current HPV vaccines can drastically reduce the incidence and 
mortality of several types of cancer, including cervical, anal, and 
oropharyngeal cancers that are caused by infection with certain strains 
of HPV.
    Still, NCI recognizes that these successes are incomplete, and 
therefore invests heavily in efforts to address several pertinent 
behavioral and biological questions. For instance, despite dramatic 
declines in the use of tobacco, about 18 percent of Americans continue 
to smoke. New approaches are needed to convince young people not to use 
tobacco and to convince current smokers to quit. Use of HPV vaccines 
remains far from the desired levels among adolescent girls and boys in 
the United States, as the February 2014 report from the President's 
Cancer Panel emphasized. Better methods to promote the use of these 
potentially lifesaving vaccines are needed, at the same time as the 
dosing schedules and the protective breadth of the vaccines are 
improved.
                               conclusion
    An important measure of the overall success of NCI's work is the 
annual ``Report to the Nation,'' which describes trends in the 
incidence and death rates in the United States for many types of 
cancer. As has now been true for over a decade, the most reliable 
indicator--death rates from all cancers combined for men, women, and 
children--continues to decline by about one and a half percent per 
year. This reduction represents the savings of an enormous number of 
years of life and can be ascribed in large measure to the work of the 
NCI to prevent and treat cancers more effectively.
    Still, although mortality rates have been decreasing for most 
cancers, progress has not occurred as rapidly as desired, and for some 
cancers the numbers have not improved--or have worsened. Thus, much 
work remains. But the overall success apparent from both the public 
health data and recent achievements in the laboratory and clinical 
sciences inspires the NCI's conviction that expanded efforts on all 
frontiers of cancer research will produce better health in the United 
States and around the globe.
                                 ______
                                 
              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 2015 budget of $2,987,685,000 includes an 
increase of $4,948,000 over the fiscal year 2014 enacted level of 
$2,982,737,000.
    NHLBI's highest priorities for research investment are conditions 
that contribute substantially to the global burden of disease. Heart 
and lung diseases are the leading causes of death, disability, and 
rising healthcare costs from non-communicable diseases in the United 
States and worldwide. Research supported by the NHLBI has contributed 
to dramatic improvements in longevity, quality of life, and the wealth 
of the Nation. Deaths from cardiovascular disease, for example, have 
dropped by 70 percent in the past 40 years. This success reflects a 
balanced approach to supporting discovery science that spans basic, 
clinical, and population research. As accountable stewards seeking to 
maximize the public's return-on-investment, we are committed to 
continually improving our approach to strategic priority-setting and 
systematic evaluation of our portfolio to ensure the highest possible 
impact on science and health.
    Reflecting upon the NHLBI's legacy of success, many of the previous 
advances involved interventions at the latter stages of chronic 
disease. The fiscal year 2015 budget envisions a research agenda that 
elucidates the underlying mechanisms of disease such that clinicians 
can more accurately predict at-risk individuals and tailor preventive 
interventions for disease long before symptoms and irreversible damage 
occur. Our strategic vision is guided by the breathtaking scientific 
opportunities at hand and public health needs, in consultation with 
domain-experts at the leading edge of discovery science. The fiscal 
year 2015 budget continues a journey toward predictive, preventive 
precision medicine that holds promise for turning research-to-results, 
continuing the dramatic decline in the burden of chronic disease in our 
Nation.
                 unprecedented scientific opportunities
    Sustained investments in fundamental discovery science have led to 
new tools and technologies that stand to revolutionize medical research 
and clinical practice. Biomedical advances in congenital heart disease 
(CHD), the most common structural birth defect, have led to dramatic 
improvements in infant survival over the past 50 years, now with more 
adults living with CHD than children. However, current palliative 
approaches that repair birth defects have limitations that compromise 
the length and quality of life. Recent NHLBI-supported research, 
applying the latest genomic technologies, has identified spontaneous 
genetic mutations that increase the risk of CHD. This breakthrough 
finding is beginning to unlock the mysteries of CHD, helping to define 
what goes awry during the formation of the heart and lay the foundation 
for preventing or fixing defects in the womb. To that end, NHLBI is 
investing in regenerative medicine research to enhance the capacity of 
the heart to repair itself. The 2012 Nobel Laureate, Shinya Yamanaka, 
is part of a large inter-institutional team of NHLBI-funded 
investigators studying how to use a child's own cells to repair a 
congenital defect or create a tissue graft that could grow as a child 
ages.
    NHLBI investments in reparative biology and tissue bioengineering 
may also hold promise for accelerating new drug development platforms 
in partnership with the private sector. For example, NHLBI-funded 
investigators at Stanford University are using stem cells derived from 
adult tissue in a laboratory to create heart cells and model diseases 
such as those that perturb the electrical system of the heart in atrial 
fibrillation. These models are being used to more efficiently screen 
many novel drugs to determine efficacy as well as potential toxicities, 
augmenting the discovery pipeline.
               preempting and preventing chronic disease
    New scientific discoveries hold promise for making public health 
inroads to halt chronic diseases before they become debilitating. In 
sickle cell disease (SCD), for example, we have made great strides in 
reducing complications from the disease, such as penicillin to prevent 
fatal infections in infants, transfusions to reduce stroke risk, and 
hydroxyurea to reduce pain and hospital admissions. While these 
advances have extended lifespans from childhood into the sixth decade 
of life, they target complications not the disease itself--a disease 
that disproportionately affects African Americans (about 1 in 500 
births). We recently funded a new program that we hope will lead to the 
next generation of SCD treatments. Particularly exciting are studies 
that are attempting to raise fetal hemoglobin levels (the most powerful 
known modifier of SCD severity) through modulation of a gene called 
Bcl11A that is involved in the switch from fetal to adult hemoglobin 
during development. These studies open the door to potential treatments 
that can reactivate the fetal hemoglobin gene to inhibit the sickle 
cell shape change of red blood cells, which could preempt disease 
progression.
    Chronic obstructive pulmonary disease (COPD), the third leading 
cause of death, is a prime example of a chronic disease in which 
biomedical research advances have ameliorated symptoms; yet most 
interventions fail to dramatically alter the natural course of the 
disease. There is a critical need to identify at-risk individuals 
earlier in the disease process to prevent disease progression. NHLBI's 
COPDgene study is integrating genetics and imaging studies to 
characterize pre-clinical subtypes of COPD. Such characterization can 
enable clinicians to detect subtle changes in lung function and 
structure long before symptoms develop, conventional clinical tests 
show abnormalities, or progressive lung damage occurs. This leading-
edge research points to a horizon of individualized, precision medicine 
to preempt chronic lung disease.
           translating discoveries into public health impact
    While basic science is the cornerstone of scientific discovery, it 
is the beginning of a long path to public health impact. NHLBI has been 
a leader in traversing this road. Noted research initiatives like the 
Framingham Heart Study first identified the cardiovascular disease risk 
factors now addressed in routine physicals, which led to basic research 
that won Brown and Goldstein the Nobel Prize for their research on 
cholesterol metabolism--setting the stage for the development of statin 
drugs.
    We are currently amidst the unfolding of a similar story. The 
recent discovery of a mutation in the gene PCSK9 among a family with 
very low LDL cholesterol levels and reduced risk of heart attack has 
led to basic science discoveries and the rapid development of PCSK9 
inhibitors. This public-private partnership is moving toward potential 
widespread clinical use as the next generation of cholesterol lowering 
drugs.
    We now know, however, that we must look beyond one-size-fits-all 
treatments. Population science and genetics research have clearly 
demonstrated individual differences not only in predisposition to 
disease but also in treatment response. For example, 26 million 
Americans currently suffer from asthma--the leading cause of missed 
school days for children and a driver of preventable hospitalizations 
and emergency room visits. Asthma disproportionately affects African 
Americans; African American children are twice as likely to have asthma 
as white children and, as adults, are two to three times more likely to 
die of asthma than any other racial or ethnic group. While effective 
treatments exist, they do not reach all of those in need. NHLBI will be 
seeking applications focused on identifying barriers and testing 
strategies to enhance the implementation of evidence-based practices in 
diverse communities across the Nation. Beyond the current treatments, 
next generation therapies should target these differences to achieve 
maximal benefit. NHLBI's multi-center clinical trial network, 
AsthmaNet, is beginning the Best African American Response to Asthma 
Drugs (BARD) study to compare the effectiveness of different treatments 
on the management of asthma in African Americans. BARD will also assess 
how genetics may influence an individual's response to the treatments, 
which could be a paradigm shift in addressing challenges like 
disparities in asthma care.
                               conclusion
    We are in the midst of a very exciting period in science in which 
the capacity to enhance human health has never been greater. New tools 
and technologies are daring us to envision a future that is unburdened 
by chronic heart, lung, and blood diseases--not only ensuring wellness 
but also increasing economic productivity and reducing healthcare 
costs. For example, research shows that treating patients at moderate 
risk for cardiovascular disease with statin drugs to lower cholesterol 
can reduce annual medical spending by up to $430 million. Imagine how 
much can be saved by preventive interventions earlier in the disease 
course before symptoms begin and the costs of treatment rise 
dramatically. By achieving that goal, the return-on-investment of 
biomedical research will strengthen both the health and the wealth of 
the Nation.
                                 ______
                                 
              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 2015 NINDS budget of $1,608,461,000 
includes an increase of $22,664,000 over the comparable fiscal year 
2014 level of $1,585,797,000. NINDS supports research to reduce the 
burden of neurological disorders, from basic studies of the normal 
brain through clinical trials of prevention and treatment 
interventions. Today, I will make four points: (1) the burden of 
neurological disorders is enormous; (2) past NINDS research has paid 
off; (3) opportunities for future progress are extraordinary; and (4) 
we have well informed plans to exploit these opportunities.
                    burden of neurological disorders
    Nearly 800,000 Americans experience a stroke each year, and 15 to 
30 percent of the 6.8 million stroke survivors alive today suffer 
permanent disability.\1\ 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. 
In the United States, 2.5 million people receive emergency care for a 
TBI each year, and millions more suffer mild TBI (concussions). 
Epilepsy affects 2.3 million Americans, including 1 in 26 people at 
some time in their lives. Alzheimer's disease is receiving increasing 
attention, but most people are less aware that frontotemporal dementia 
(FTD) is the most common dementia in people under age 60, and vascular 
dementia, which affects blood vessels in the brain, is the second most 
common dementia overall and is so closely intertwined with Alzheimer's 
disease that most dementia patients have a combination of the two. 
Parkinson's disease, spinal cord injury, cerebral palsy, multiple 
sclerosis, and hundreds of rare diseases that affect children and 
adults add to the immeasurable human and economic burden.
---------------------------------------------------------------------------
    \1\ Statistics for stroke, TBI, and epilepsy from U.S. Centers from 
Disease Control and Prevention www.cdc.gov
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                   progress for patients and families
    NINDS research drives progress directly, and indirectly catalyzes 
private sector advances. NINDS studies on risk factors and prevention 
contributed to a decline in the age-adjusted stroke death rate by 35.8 
percent from 2000 to 2010; the actual number of stroke deaths fell 22.8 
percent.\2\ NINDS research developed the only approved emergency drug 
therapy that restores blood flow to the brain following stroke, 
increasing likelihood of recovery with little or no disability by 30 
percent. Research has also demonstrated, defying conventional wisdom, a 
wider window of opportunity for stroke rehabilitation--even patients 
who start rehabilitation as late as 6 months after a stroke can 
improve, and patients can continue to improve 1 year after a stroke. 
For people with epilepsy, an implantable device approved this year 
senses impending seizures and delivers electrical pulses to stop them. 
Long-term NINDS research provided the essential foundation for private 
sector development of this device. Similarly, NINDS research directly 
and indirectly contributed to deep brain stimulation (DBS) therapies 
now in use for Parkinson's, essential tremor, and dystonia and under 
clinical testing for many other disorders, as well as to development of 
drugs for multiple sclerosis--10 are now on the market, including the 
first oral drugs. Overall, the private sector has nearly 450 medicines 
in development for neurological disorders, which would not be possible 
without the foundation of NIH research.\3\
---------------------------------------------------------------------------
    \2\ Circulation 2014; 129:e28-e292
    \3\ 2013 Report: Medicines in Development for Neurological 
Disorders, Pharmaceutical Researchers and Manufacturers of America 
http://www.phrma.org/innovation/meds-in-development
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                      extraordinary opportunities
    Science and technology are opening unprecedented opportunities for 
progress against neurological disorders. Studies on the normal brain 
build the foundation. Notable recent advances, for example, revealed 
how the brain clears out debris during sleep, how molecular structures 
called ion channels control electrical activity, and the first human 
``connectome'' maps, providing astonishing views of the basic wiring 
diagram of living, thinking human brains. Advances in stem cell biology 
now enable researchers to reproduce in cell culture key steps in 
amyotrophic lateral sclerosis (ALS) and other disorders using brain 
cells derived from patients' own skin cells. Basic science has led to 
new insights that explain how chronic pain is wired in the brain, what 
happens in the brain following a concussion, and how cell-to-cell 
propagation of abnormally folded proteins could drive progression of 
Parkinson's, Alzheimer's, and other neurodegenerative disorders. New 
gene sequencing methods and high throughput gene silencing technologies 
have accelerated the discovery of genes that cause epilepsy and 
revealed potential new drug targets for Parkinson's disease. In a few 
dramatic cases, gene discoveries have led directly to treatments that 
help patients with rare disorders, including subtypes of dystonia and 
childhood neurodegenerative disease, but more often painstaking 
translational research is required to advance genetic and other 
discoveries toward therapies. Among the many examples, promising 
reports in laboratory animals this year demonstrated a drug therapy 
that prevented the development of epilepsy, cell transplants that 
controlled seizures, natural growth factor rescue of neonatal brain 
injury, therapies that improved cognition in Down syndrome, and a hand 
neuroprosthesis that restored touch sensation as well as movement.
                        programs and priorities
    NINDS relies heavily upon the wisdom and ingenuity of researchers 
throughout the United States to propose and evaluate the best 
scientific opportunities. Complementing investigator-initiated 
programs, NINDS initiatives target unmet opportunities or public health 
needs. Institute priorities reflect strategic and disease-specific 
planning that engages the scientific community and the public, and 
rigorous evaluation of programs, closing those that have met their 
goals or are no longer appropriate for today's science. Recent plans 
focused on stroke, epilepsy, Parkinson's disease, and Alzheimer's 
Disease-Related Dementias. Among recent initiatives:
  --the Stroke Trials Network will determine more quickly and at less 
        cost what treatment, prevention, and rehabilitation strategies 
        work best.
  --new Epilepsy Centers without Walls will target Sudden Unexplained 
        Death in Epilepsy (SUDEP) and disease modification or 
        prevention.
  --the Parkinson's Disease Biomarkers Program is developing assessment 
        tools that will overcome roadblocks to more effective clinical 
        trials.
  --the International TBI Research Initiative, coordinated with the 
        European Union and the Canadian Institute of Health Research, 
        will answer questions on care and classification of TBI that 
        have confounded development of interventions.
  --two major cooperative studies are investigating the long-term 
        changes in the brain years after a single TBI or multiple 
        concussions, coordinated via the Foundation for NIH's Sports 
        and Health Research Program, which was established with a 
        donation from the National Football League.
  --the NeuroBioBank, NINDS Human Genetics Repository, Federal 
        Interagency TBI Research database, Common Data Elements 
        Program, and an epilepsy clinical genetics data repository are 
        examples of new and continuing resource initiatives that 
        empower individual investigators and promote data sharing.
    Finally, and most ambitiously, the President's Brain Research 
through Advancing Innovative Neurotechnologies (BRAIN) Initiative will 
dramatically improve tools to understand heretofore unapproachable 
questions about how networks, or circuits, of brain cells enable us to 
perceive, think, and act. There are many reasons for confidence that 
this basic research initiative will ultimately advance progress against 
disease. Autism, dystonia, and epilepsy, for example, are fundamentally 
disorders of brain circuitry, and stroke, Parkinson's, and Alzheimer's 
disease disrupt brain circuits as nerve cells die. Even with our 
limited understanding of brain circuits and imprecise technologies for 
altering them, interventions that compensate for malfunctioning brain 
circuits already produce remarkable results. For example, DBS reverses 
symptoms for many people with Parkinson's disease and dystonia, and 
paralyzed people have controlled a robotic arm by signals directly 
monitored from their brains' movement control circuits. It is perhaps 
obvious that better understanding of brain circuits and tools to 
influence their activity would greatly improve these interventions, but 
history teaches that the most important payoffs of the BRAIN 
Initiative, as for basic research generally, may be entirely 
unforeseen.
                                 ______
                                 
           Prepared Statement of Christopher P. Austin, M.D.
    Mr. Chairman, Ranking Member, and Members of the Committee: Thank 
you for the opportunity to present to you the President's budget 
request for the National Center for Advancing Translational Sciences 
(NCATS) for fiscal year 2015. The fiscal year 2015 budget for NCATS is 
$657,471,000, which represents an increase of $25,075,000 over the 
fiscal year 2014 level of $632,396,000. The request includes 
$471,719,000 for the Clinical and Translational Science Awards (CTSA) 
program and $29,810,000 for the Cures Acceleration Network (CAN).
                         translational research
    In recent years, biomedical research has led to significant 
advances in our understanding of human biology. We have sequenced the 
human genome, explored the potential of stem cells, and discovered RNA 
interference. All of these advances have been celebrated as holding 
enormous promise for improving human health, but the road from promise 
to tangible improvements in public health has been long, complex and 
full of obstacles. NCATS aims to turn these game-changing discoveries 
into treatments for patients by addressing the ``translational 
sciences'' needed to close the gap. Translational sciences comprise the 
process of turning observations in the laboratory and clinic into 
effective interventions that improve the health of individuals and the 
public--from diagnostics and therapeutics to medical procedures and 
behavioral changes.
    NCATS takes a system-wide approach to diseases and the 
translational science process. It serves as an ``adaptor'' to connect 
basic, clinical and public health research and as a ``convener'' for 
disparate organizations that play roles in the process of turning 
discoveries into health improvements. Every NCATS initiative is a 
collaboration with partners in the public, private, government or 
nonprofit sector. The Center is committed to developing technologies 
and paradigms that improve the efficiency and effectiveness of one or 
more steps in the translational process, demonstrating that these 
innovations work in specific use cases, and disseminating the 
translational advances widely to catalyze improvements in all 
translational efforts with the ultimate and critically important goal 
of improving health.
                          mission into action
    One NCATS initiative that exemplifies these goals is the 
Discovering New Therapeutic Uses for Existing Molecules program. This 
program matches academic research groups with pharmaceutical companies 
to explore new disease indications for investigational compounds that 
are no longer being pursued by the pharmaceutical companies. The aim is 
to address several challenges in the translation process: the need for 
treatments for the several thousand diseases that have no effective 
therapy, the complicated process of negotiating agreements between 
parties who want to work together, and the largely ad hoc process by 
which academic and pharmaceutical researchers develop collaborative 
projects. In fiscal year 2013, NCATS funded nine projects covering 
eight disease areas, including Alzheimer's disease, Duchenne muscular 
dystrophy and schizophrenia. The program already has resulted in 
positive outcomes. Within 3 months of the grantees receiving funds, 
three compounds were being tested in humans for new uses--two to treat 
schizophrenia and one to treat Alzheimer's disease. In addition, the 
time to establish collaborations between industry and academics has 
been shortened to only 13 weeks from the more typical 9 months to a 
year. NCATS will solicit a second group of projects in fiscal year 
2014.
    The NCATS emphasis on innovation is central to its collaboration 
with the National Eye Institute and Organovo (which makes 3-D tissue 
printers) to develop 3-D, architecturally accurate eye tissue. Such 
tissues have the potential to accelerate the drug discovery process--
enabling treatments to be developed faster and at a lower cost--by 
giving researchers a more accurate view of how drugs will behave in 
human cells before those drugs ever enter clinical trials.
    NCATS serves as a catalyst to increase the efficiency of the 
translational ecosystem, as illustrated by the formation of a research 
team that included scientists from the Johns Hopkins School of Medicine 
and the NCATS Assay Development and Screening Technology Laboratory. 
This team developed new methods to overcome several translational 
roadblocks and was able to demonstrate their effectiveness by 
identifying a promising new compound that prevents the death of cells 
in the eye from glaucoma, a disease that can lead to blindness. Working 
together, the collaborators were able to solve a problem that none of 
them could address alone.
                    translational research spectrum
    Strengthening and supporting the entire spectrum of translational 
research with the ultimate aim of improved public health is a top 
priority for NCATS, and the CTSA program is crucial for these efforts. 
The CTSA program develops new technologies, methods, resources and 
operational paradigms that catalyze clinical research progress, and 
supports the training and career development of translational 
researchers. In June 2013, the Institute of Medicine (IOM) issued a 
report following a review of the CTSA program. The report recommended 
that NCATS take a more active role in the program's governance and 
direction, formalize the evaluation processes of the program, advance 
innovation in education and training programs, and ensure that the 
patient community participates in all phases of research. Since the 
publication of the report, the Center has increased programmatic and 
fiscal management of the grants that support the CTSA program and has 
streamlined the governance of the consortium, consulting closely with 
the CTSA Principal Investigators. A Working Group of the NCATS Advisory 
Council was established in December 2013 to provide input on measurable 
objectives for the program. The Working Group will submit its report to 
the NCATS Advisory Council in May 2014.
                         focus on rare diseases
    NCATS is deeply committed to developing treatments for rare 
diseases, which are defined in the U.S. as affecting fewer than 200,000 
individuals. There are approximately 6,500 rare diseases, but only 250 
have treatments. The NCATS Therapeutics for Rare and Neglected Diseases 
(TRND) program advances potential treatments for rare and neglected 
diseases to first-in-human trials, an approach known as ``de-risking.'' 
This strategy makes new drugs more commercially attractive to 
biopharmaceutical companies, despite the small patient population that 
is characteristic of these diseases. For example, in 2013, a clinical 
trial was started to evaluate a drug candidate called cyclodextrin as a 
possible treatment for Niemann-Pick disease type C1 (NPC1), a rare and 
fatal genetic brain disease affecting children. A TRND-led team of more 
than 20 investigators from NIH, academia, a pharmaceutical company, and 
patient groups developed cyclodextrin as a treatment as well as an NPC 
biomarker to guide its clinical development. An Investigational New 
Drug application for cyclodextrin was approved by the FDA, and a Phase 
I clinical trial currently is ongoing.
                       cures acceleration network
    CAN was authorized to advance the development of high-need cures 
and reduce significant barriers between research discovery and clinical 
trials. At NCATS, CAN is intended to advance initiatives designed to 
address scientific and technical challenges that impede translational 
research.
    Currently, CAN supports the Tissue Chip for Drug Screening Program, 
which is a partnership with the Defense Advanced Research Projects 
Agency (DARPA) and the FDA to develop 3-D human tissue chips that 
accurately model the structure and function of human organs, such as 
the lung, liver and heart. These devices will enable researchers to 
predict harmful health effects of new drugs more accurately, thus 
addressing one of the main reasons that drug studies often fail.
    NCATS has had success moving projects forward with its rare disease 
therapeutics program, but there are significantly fewer groups working 
on developing medical devices, for which there is a great need. NCATS 
could launch a comprehensive collaborative effort to accelerate device 
development as part of the next phase in the CAN program.
                               conclusion
    These projects are just a few examples of the exciting and 
innovative activities underway at NCATS. Though the Center is still 
relatively new, early successes demonstrate how its distinctive 
approaches can help solve some of the most challenging problems in 
translational science. We will build on our accomplishments over the 
past 2 years to accelerate our programs further in fiscal year 2015. I 
look forward to sharing more of our achievements with you as NCATS 
continues to evolve.

    [Clerk's note.--The following Institutes of the National 
Institutes of Health did not appear before the subcommittee 
this year. Chairman Harkin requested these Institutes to submit 
testimony in support of their fiscal year 2015 budget request. 
Those statements follow:]

    Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S.
    Mr. Chairman and Members of the Subcommittee: 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 2015 NIEHS budget of $665,080,000 
includes an increase of $556,000 from the comparable fiscal year 2014 
level of $664,524,000. The NIEHS Strategic Plan, Advancing Science, 
Improving Health continues to guide efforts toward fulfilling our 
mission to discover how the environment affects people in order to 
prevent both acute and chronic illness.
                             breast cancer
    NIEHS continues its robust investment into environmental factors 
affecting breast cancer, with the goal of learning how we can prevent 
this widespread disease. NIEHS and the National Cancer Institute (NCI) 
collaborated to support the Interagency Breast Cancer and Environmental 
Research Coordinating Committee, whose report, Prioritizing Prevention, 
recommends strategies to mitigate the environmental causes of breast 
cancer. NIEHS supports several major epidemiological and translational 
breast cancer initiatives. The Breast Cancer and the Environment 
Research Program is a transdisciplinary initiative cosponsored by NCI 
and NIEHS, in which basic scientists, epidemiologists, clinicians, and 
community partners work together to examine the effects of 
environmental exposures that may predispose a woman to breast cancer 
throughout her life, including exposures during puberty, menopause, 
pregnancy, and other ``windows of susceptibility.'' The NIEHS Sister 
Study has recruited a cohort of 50,884 U.S. and Puerto Rican women with 
a sister diagnosed with breast cancer, to prospectively study 
environmental and genetic factors that influence breast cancer risk and 
survival. More than 1,500 incident breast cancers have been diagnosed 
to date. A May 2013 publication from these researchers showed that DNA 
methylation profiling in blood samples may hold promise for breast 
cancer detection and disease risk prediction. The Agricultural Health 
Study, a collaborative effort by NCI, NIEHS, the National Institute for 
Occupational Safety and Health (NIOSH), and the Environmental 
Protection Agency (EPA), includes a comprehensive evaluation of many 
commonly used herbicides and pesticides and their potential impact on 
risk of breast cancer among 32,000 women who are married to pesticide 
applicators (primarily farmers).
                      environment and autoimmunity
    NIEHS supports scientists who are exploring how environmental 
exposures can cause immune system dysfunction. There is evidence that 
autoimmune diseases likely involve an environmental component. 
Therefore, the Environmental Autoimmunity Group in the Clinical 
Research Program at NIEHS is looking at the relationship between 
environmental factors and autoimmune disease. Autoimmune diseases 
result from an immune response directed against the body's own tissues 
and they collectively afflict approximately 24.5 million Americans, 
with women disproportionately affected. The cause(s) of autoimmune 
disorders remain largely unknown and are likely multifactorial 
involving both genetic and environmental influences. In 2013, NIEHS 
released a Funding Opportunity Announcement (FOA) to enable a better 
understanding of the links between exposures and autoimmune disease.
    NIEHS continues to support autoimmune disease research in the 
underserved community of Libby, Montana where the population has been 
exposed to asbestos minerals as a byproduct of vermiculite ore mining. 
Of particular concern is early childhood exposure, since susceptibility 
may be increased during this life stage. Recent efforts to characterize 
children's exposure in Libby estimated up to 15 times higher levels of 
airborne asbestos concentrations during outdoor activities and 73 
percent of the study participants indicated these activities occurred 
in the presence of children.\1\ NIEHS grantees are investigating 
whether childhood asbestos exposures in Libby are associated with 
pulmonary disease later in life.
---------------------------------------------------------------------------
    \1\ Ryan PH et al. Childhood exposure to Libby amphibole during 
outdoor activities. May 22, 2013. J. Expo. Sci. Environ. Epidemiol. 
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/
?term=PMID%3A+23695492
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                 environment and neurological disorders
    Evidence indicates there is both an environmental and genetic 
component in neurological disorders. NIEHS funds research to advance 
the understanding of environmental factors and gene-environment 
interactions related to neurodegenerative diseases and to help create 
new prevention and treatment approaches. At the NIEHS Centers for 
Neurodegeneration Science (CNS) and in partnerships with the National 
Institute of Neurological Disorders and Stroke (NINDS) and National 
Institute on Aging (NIA), teams of top scientists from different 
disciplines collaborate to examine the root causes of neurodegenerative 
diseases. CNS researchers study how exposure to pesticides, metals 
(e.g. arsenic, lead), and other chemicals affect the development of 
neurodegenerative diseases such as Parkinson's and Alzheimer's disease. 
NIEHS recently published two Funding Opportunity Announcements to 
expand neurological research: one on environmental exposures and 
Alzheimer's disease, and the other on environmental exposures and 
neurodegenerative disease.
    Autism is a highly variable neurodevelopmental disorder, which is 
likely influenced by environmental exposures. NIEHS-funded researchers 
have published work indicating prenatal vitamins might reduce the risk 
of having children with autism.\2\ Exposure to air pollution during 
pregnancy and during the first year of life was also associated with 
autism.\3\ \4\ \5\ NIEHS funds two key autism studies: the Childhood 
Autism Risks from Genetics and the Environment (CHARGE) study, and the 
Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) study. 
In April 2014, NIEHS hosted a community virtual forum on autism and the 
environment that was webcast live and featured a panel of autism 
research experts.
---------------------------------------------------------------------------
    \2\ Int J Epidemiol. 2014 Feb 11. [Epub ahead of print] Maternal 
lifestyle and environmental risk factors for autism spectrum disorders. 
Lyall K1, Schmidt RJ, Hertz-Picciotto I.
    \3\ Epidemiology. 2014 Jan;25(1):44-7. Autism spectrum disorder: 
interaction of air pollution with the MET receptor tyrosine kinase 
gene. Volk HE1, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R, 
Campbell DB.
    \4\ JAMA Psychiatry. 2013 Jan;70(1):71-7. doi: 10.1001/
jamapsychiatry.2013.266. Traffic-related air pollution, particulate 
matter, and autism. Volk HE1, Lurmann F, Penfold B, Hertz-Picciotto I, 
McConnell R.
    \5\ Autism Res. 2013 Aug;6(4):248-57. doi: 10.1002/aur.1287. Epub 
2013 Mar 11. Prenatal and early-life exposure to high-level diesel 
exhaust particles leads to increased locomotor activity and repetitive 
behaviors in mice. Thirtamara Rajamani K1, Doherty-Lyons S, Bolden C, 
Willis D, Hoffman C, Zelikoff J, Chen LC, Gu H.
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                research update on endocrine disruptors
    NIEHS is the leading government agency funding research on the 
human health effects of exposure to endocrine disrupting chemicals 
(EDCs). EDCs have the potential to interfere with a host of 
physiological functions, contributing to the development of costly and 
devastating illnesses such as obesity, diabetes, attention deficit 
hyperactivity disorder (ADHD) and behavioral disorders, asthma, 
endometriosis and uterine fibroids, reproductive disorders and 
infertility, and breast, uterine, and prostate cancers. Exposures to 
EDCs have been documented across the population, with fetuses and young 
children at greater risk due to their stages of rapid development. 
NIEHS is currently funding over 100 grants examining effects of EDCs 
including bisphenol A (BPA), arsenic, pesticides, flame retardants, and 
others.
    NIEHS has focused particular efforts on BPA, in part due to its 
ubiquity, that results in daily exposures for most people, mainly 
through diet. The Consortium Linking Academic and Regulatory Insights 
on BPA Toxicity (CLARITY--BPA) research program is a collaborative 
effort of the NIEHS, the National Toxicology Program (NTP), the Food 
and Drug Administration's National Center for Toxicological Research, 
and academic researchers studying a range of health endpoints, while 
also establishing new testing standards and methodologies. A recent 
study of another EDC, phthalates, shows that levels of some 
plasticizers have fallen since a Federal ban on their use in children's 
products and voluntary removal from many consumer goods.\6\ However, 
research at Brown University suggests that replacement chemicals may be 
just as damaging to the reproductive development of boys.\7\
---------------------------------------------------------------------------
    \6\ Zota AR, Calafat AM, Woodruff TJ. 2014. Temporal trends in 
phthalate exposures: findings from the National Health and Nutrition 
Examination Survey, 2001-2010. Environ Health Perspect; http://
www.ncbi.nlm.nih.gov/pubmed/24425099.
    \7\ Saffarini CM, Heger NE, Yamasaki H; Liu T, Hall SJ, Boekelheide 
K. 2012. Induction and persistence of abnormal testicular germ cells 
following gestational exposure to di-(n-butyl) phthalate in p53-null 
mice. J Andrology; 33(3):505-513. http://www.ncbi.nlm.nih.gov/pmc/
articles/PMC3607946
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                   research update on gulf oil spill
    The release of millions of gallons of crude oil following the 2010 
Deepwater Horizon (DWH) disaster posed unpredictable risk to over 
130,000 workers trained and potentially involved in various remediation 
activities and to the people living along the Gulf Coast. To date, 
there have been limited studies on the human health effects of oil 
spills, especially long-term effects. The NIEHS Gulf Long-term Follow-
up Study (GuLF STUDY), funded in part by the NIH Common Fund, is 
investigating potential short- and long-term health effects associated 
with oil spill cleanup activities. The GuLF STUDY has enrolled 32,786 
individuals and has completed home visits for 11,200 participants, 
during which clinical measurements were taken and biospecimens were 
collected for future research.
     NIEHS leads the DWH Research Consortia that funds a network of 
academic and community partners to study health effects in people 
residing in regions affected by the disaster. These studies are 
examining resilience at the individual and community levels, 
perceptions of risk among women and children, and the potential 
contamination of seafood in the Gulf (Strategic Plan Goals 4-6). While 
NTP is conducting research to increase our understanding of the 
toxicology of crude oil, NIEHS grantees have preliminary results that 
suggest increased depression and anxiety among Gulf Coast residents, 
but also suggest strong community networks promote resilience.
                                 ______
                                 
            Prepared Statement of Josephine P. Briggs, M.D.
    Mr. Chairman and Members of the Committee: As the Director of the 
National Center for Complementary and Alternative Medicine (NCCAM) of 
the National Institutes of Health (NIH), I am pleased to present the 
President's fiscal year 2015 budget request for NCCAM. The fiscal year 
2015 budget includes $124,509,000, which is $384,000 more than the 
comparable fiscal year 2014 appropriation of $124,125,000.
    The National Center for Complementary and Alternative Medicine 
(NCCAM) is the Federal Government's lead agency for supporting 
scientific research on complementary practices and integrative health 
interventions. NCCAM's mission is to define, through rigorous 
scientific investigation, the usefulness and safety of such practices 
and their roles in improving health and healthcare.
               complementary and integrative health care
    Complementary and integrative health practices are defined as 
having origins outside of mainstream conventional medicine and include 
both self-care practices like meditation, yoga, and dietary 
supplements, as well as healthcare provider administered care such as 
acupuncture, chiropractic, osteopathic and naturopathic medicine. As 
these modalities are increasingly integrated into mainstream 
healthcare, NCCAM is committed to developing the scientific evidence 
needed by the public, healthcare professionals and health policymakers 
to make informed decisions about the use and integration of these 
various practices.
            use of complementary and integrative health care
    For the past decade, some 30 to 40 percent of Americans have used 
complementary and integrative health practices, according to data from 
the National Health Interview Survey (NHIS) conducted by the Centers 
for Disease Control and Prevention (CDC). The NHIS data shows that 
Americans are willing to pay for these services, spending some $34 
billion in 2007, which represented 1.5 percent of total health 
expenditures and 11 percent of out-of-pocket costs. NCCAM has worked 
with the CDC since 2002, to develop the questions on complementary 
healthcare that are included in the NHIS every 5 years (2002, 2007, and 
2012). Results from the latest survey are currently being analyzed for 
publication later this spring. Analysis will include, for the first 
time, a comparison of regional variations in use of complementary 
health practices by adults in the United States. We also look forward 
to the first detailed look at integration of complementary 
interventions into private medical practice when the results of the 
2012 National Ambulatory Medical Care Survey, which involved interviews 
of 30,000 physicians, are analyzed. NCCAM worked closely with the CDC 
to develop the questions used in this survey, as well.
                        impact on public health
    NCCAM's approach to setting priorities and investment in research 
is guided by the need for rigorous evidence that ultimately may have a 
significant impact on public health. One example of this approach 
involves a major clinical trial supported jointly by NCCAM and the 
National Heart, Lung, and Blood Institute examining the efficacy of 
using EDTA-based chelation therapy to reduce cardiovascular disease and 
prevent heart attacks. The trial, which involved 1,700 patients, showed 
a modest reduction in cardiovascular events for adults aged 50 and 
older who had suffered a prior heart attack. However, the results from 
a secondary analysis of the trial data suggest that the chelation 
treatments produced a marked reduction in cardiovascular events and 
death in patients with diabetes but not in those without diabetes. 
Addressing cardiovascular disease in diabetics is an important public 
health challenge, and better treatment options are required. As this 
study was not designed to discover how or why chelation might benefit 
patients with diabetes, further investigation is needed. Thus, NCCAM is 
exploring the possibility of a follow-up study in collaboration with 
several other NIH Institutes.
             reducing pain and improving symptom management
    According to the Institute of Medicine, pain is a major public 
health problem affecting more than 100 million Americans and costing 
the Nation over $600 billion in medical costs and lost productivity. 
Pain is also the most common reason Americans turn to complementary and 
integrative health practices, as conventional medicine often provides 
incomplete relief. Therefore, pain research is a top priority for 
NCCAM. As such, we continue to invest in research on several promising 
approaches for treating pain, such as spinal manipulation, massage, 
yoga, meditation, and acupuncture. We are particularly interested in 
understanding how these interventions work, for what type of pain 
condition, and for determining the optimal method of practice and 
delivery. Toward this end, NCCAM partners with others in supporting 
research initiatives, participates in the NIH Pain Consortium, and 
leads an NIH Task Force to improve standards for research on chronic 
low back pain (cLBP). The cLBP Task Force has developed common 
standards, measures, and other tools for clinical research on cLBP, and 
a report is expected to be published in The Journal of Pain later this 
year.
    Another important collaborative effort is our partnership with the 
National Institute on Drug Abuse and the Department of Veterans Affairs 
to foster research on complementary and integrative approaches to 
managing pain and other symptoms experienced by military personnel and 
veterans. A number of grant applications were submitted in response to 
our joint solicitation, and we anticipate funding multiple studies 
later this fall.
    One area of particular interest is the means by which complementary 
health practices affect the perception of pain by the brain. 
Specifically, we seek to understand the mechanisms by which emotions, 
attention, and context modulate pain. Using neuroimaging and cutting-
edge technologies, our intramural research program (IRP) is exploring 
the central mechanisms of pain and its modulation, with the long-term 
goal of improving clinical management of chronic pain through the 
integration of pharmacological and non-pharmacological complementary 
health approaches. NCCAM's IRP engages and leverages the exceptional 
basic and clinical neuroscience efforts across NIH.
                 advancing research on natural products
    Another important area of emphasis for NCCAM is research on natural 
products. In addition to exploring the underlying biological effects 
and mechanisms of natural products, such as dietary supplements, herbs, 
botanicals, and probiotics, we are concerned about their safety. While 
there is widespread use of these products by the public, there is 
limited scientific evidence about their effectiveness and safety. In 
addition to gaining greater understanding of whether natural products 
are effective or safe when used alone, there is a need to study how 
they interact with prescription medications. This is very important 
because many patients taking prescription medications also use natural 
products, such as dietary supplements, herbs and probiotics. To 
investigate these issues, NCCAM will launch an initiative to develop 
rigorous methods to evaluate potential interactions between natural 
products and medications. The ultimate goal is to ensure that 
consumers, healthcare providers, and health policymakers are better 
informed of the potential risks and/or benefits associated with the use 
of natural products in combination with medications.
    To propel needed innovations in technology and methodology for 
research on natural products, NCCAM and the NIH Office of Dietary 
Supplements are supporting the establishment of a Center for Advancing 
Natural Products Technology and Innovation. The Center is expected to 
better support the needs of the natural products community while 
reducing resource redundancies.
               providing useful information to the public
    NCCAM provides objective, evidence-based information to scientists, 
healthcare providers, and the general public through a variety of 
approaches, including emerging technology and platforms (i.e., video, 
social media, and mobile applications) and an information-rich Web site 
(www.nccam.nih.gov). Through these approaches, science-based 
information on the safety and efficacy of complementary and integrative 
health practices--already in wide public use--is made available to a 
broad audience.
                               conclusion
    NCCAM continues to support research, collaborate with others, and 
leverage partnerships to build the scientific evidence needed by 
consumers, healthcare professionals, and health policymakers regarding 
the safety and value of complementary and integrative health practices.
                                 ______
                                 
           Prepared Statement of Roger I. Glass, M.D., Ph.D.
    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 2015 
FIC budget of $67.776 million includes an increase of $0.292 million 
more than the fiscal year 2014 enacted level of $67.484 million.
    The United States and the NIH have historically been at the 
forefront of major scientific discoveries that have improved health 
here at home and around the world. Building on these successes, 
ambitious health targets for the future now seem possible--such as a 
decrease in the overall mortality rate of children under the age of 5, 
to 20 deaths per 1,000 over the next two decades and an AIDS-free 
generation. Reductions in morbidity and mortality from non-communicable 
diseases have also begun to affect populations worldwide. At this 
critical juncture, the Fogarty International Center mission and 
investments will continue to accelerate the pace and progress of 
research, engage the best and brightest minds by building capacity at 
research institutions across the globe, and develop the evidence needed 
to confront health challenges wherever they occur. By continuing to 
invest in training outstanding early-career investigators and 
developing future global health research leaders, Fogarty will advance 
the goals and sustain the leadership of the NIH and the U.S. Government 
in biomedical research, while improving the health of Americans and 
populations worldwide.
           today's basic science for tomorrow's breakthroughs
    Non-communicable diseases and disorders (NCDs) are rapidly becoming 
the dominant causes of poor health in all low and middle-income country 
(LMIC) regions \1\ except sub-Saharan Africa, where they are second 
only to HIV/AIDS. For example, World Health Organization data suggest 
that one billion people worldwide suffer from some type of mental, 
neurological or substance abuse disorder.
---------------------------------------------------------------------------
    \1\ LMIC is a World Bank designation for the classification of 
economies, based on Gross National Income (GNI) per capita. Low income 
countries have a GNI per capita of $1,035 or less, and middle income 
countries have a GNI per capita of $1,036-$12,615.
---------------------------------------------------------------------------
    In collaboration with eight NIH Institutes and Centers (ICs), 
Fogarty's Brain Disorders in the Developing World: Research Across the 
Lifespan program supports cutting-edge basic science research in LMICs 
on the nervous system. This research could lead to important new 
diagnostics, prevention and treatment strategies, and interventions of 
direct relevance to both LMIC and U.S. populations. For example, 
Argentinian scientists, in collaboration with Northwestern University, 
are studying neuroprotective gene therapy in a preclinical trial. This 
team demonstrated that a unique vector gene delivery system using two 
powerful neuroprotective molecules could be effectively injected over 
time restoring neuronal function. Future studies will use magnetic 
nanoparticles to perform targeted gene therapy with the goal of 
treating neurodegenerative disease such as Parkinson's, the second-most 
common neurological disease in the United States, affecting 
approximately 1 million Americans (National Parkinson Foundation).
                    nurturing talent and innovation
    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, enabling them to effectively collaborate with foreign 
partners in diverse, low-resource international settings to confront 
global health challenges. Fogarty supports these hands-on, clinical 
research training experiences in LMICs in close partnership with a 
number of NIH ICs, providing experiences that encourage U.S. 
investigators to creatively approach problems under constraints that 
may not exist in high-income settings. Scientists trained with Fogarty 
support have conducted research on cardiovascular disease in Kenya, 
surgical capacity in Rwanda, mental health impacts of slum-dwelling in 
India, and the link between breast cancer and osteoporosis in China.
    Solving many of today's complex public health problems requires the 
engagement of investigators from a wide variety of fields. Fogarty's 
Framework Programs for Global Health Innovation awards support efforts 
to bring biomedical scientists together with students from various 
disciplines-- such as engineering, nutrition, business, law, 
environmental science, social sciences, agriculture and public health--
to develop research training initiatives that encourage innovative, 
health-related products, processes and policies. This program supports: 
scientists at Michigan State University studying interactions between 
agriculture, water resource utilization and malaria in Malawi; grantees 
at Northwestern University, Chicago, and the University of Cape Town, 
South Africa training researchers in developing healthcare technologies 
in Nigeria; and scientists at Tufts University School of Medicine, 
Boston, and Christian Medical College, Vellore, India developing a 
training program in translational research related to non-communicable 
and infectious diseases. These international teams are identifying 
critical health needs and conducting the research needed to develop and 
test novel solutions.
the path forward: addressing dual burdens of disease and harnessing the 
 information and communication technology revolution for global health 
                                research
    For over 25 years, Fogarty has contributed to the U.S. Government 
fight against HIV, training and supporting some of the world's foremost 
vaccine and biomedical researchers. As the global burden of disease 
shifts to a greater level of NCDs, Fogarty programs will continue 
critical work in HIV research training while also responding to both 
the NCD epidemic through research and training programs and the nexus 
between the HIV and NCD epidemics, represented by NCD co-morbidities of 
HIV infection and treatment. As scientific priorities evolve to match 
the changing burden of disease, Fogarty research and research training 
programs will train the best and brightest researchers around the world 
and facilitate scientific collaboration that meets new priorities while 
building on existing capacity and infrastructure.
    The information and communication technology (ICT) revolution 
presents exceptional opportunities and new tools for global health 
research and research education. ICT is a broad term that encompasses 
communication devices, applications, and services, such as cell phones, 
computers, radios, videoconferencing and distance learning. Fogarty 
will expand its support of innovation in the use of ICT to generate 
knowledge, scientific exchange, and research education in the hope of 
stimulating the capacity to develop and evaluate different models of 
distance learning and other ICT strategies, as well as adapt various 
ICT platforms for the needs of research and research educational 
communities. This will enable professionals in LMIC institutions to 
determine what works best for their particular settings as they develop 
novel education tools. Students and faculty will access, teach, and 
share information in creative and transformative ways, enabling new 
approaches to collaborative learning and problem solving in partnership 
with colleagues next door and across continents.
    The enormous potential for mobile technology to impact healthcare 
and research has led to the rapid development of new health-related 
phone applications. Rigorous evaluation of health outcomes after 
implementation of these interventions are often lacking. New emphases 
are being pursued to develop mobile technologies tailored to LMIC 
settings, assess their impact on health and determine how they can be 
effectively scaled up in diverse, low-resource settings. Significantly, 
this evidence base is not only critical for LMIC populations, but can 
also be applied to healthcare in the U.S.
    These are indeed exciting times for global health with new 
opportunities for partnership within and outside the NIH, the 
introduction of transformative technologies and mutual scientific 
priorities based on a shared burden of disease across high-income and 
LMIC. Capitalizing on these developments demands a multidisciplinary 
research workforce that can function across cultures and borders to 
solve common health problems. Fogarty will continue to invest in 
training the next generation of leaders in global health research at 
home and abroad to ensure that the U.S. will continue to play a key 
role in confronting the global health challenges of today.
                                 ______
                                 
        Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2015 budget request for the National 
Institute of Nursing Research (NINR) of the National Institutes of 
Health (NIH). The fiscal year 2015 NINR budget is $140,452,000 which is 
$128,000 more than the comparable fiscal year 2014 appropriation of 
$140,324,000.
    I appreciate the opportunity to share with you a brief summary of 
some of the exciting areas of research and future scientific directions 
of NINR. The mission of NINR is to promote and improve the health of 
individuals, families, and communities. We fulfill this mission by 
supporting clinical and basic research to build the scientific 
foundation for clinical practice, prevent disease and disability, 
manage and eliminate symptoms caused by illness, enhance end-of-life 
and palliative care, and train the next generation of nurse scientists. 
Today, I offer an overview of NINR's efforts and accomplishments in 
five key scientific areas and provide examples of how the research we 
support improves quality of life, health, and wellness across the 
lifespan.
       symptom science: promoting personalized health strategies
    NINR is committed to finding new and better ways to treat the 
symptoms of chronic and acute illnesses which can cause significant 
suffering for individuals and families. While we still have much to 
learn about the unique ways people experience symptoms and respond to 
treatments, recent advances in genomics are providing new opportunities 
to develop improved, personalized strategies to address adverse 
symptoms of illness, such as pain, fatigue, and disordered sleep. By 
providing a better understanding of the basic underlying biological and 
genetic mechanisms of symptoms, NINR-supported researchers are making 
important contributions to improving health and quality of life. For 
example, one NINR-supported project found that, for pregnant women with 
depression, poor sleep was associated with higher levels of 
inflammatory chemicals in the body known as cytokines, as well as 
adverse pregnancy outcomes such as preterm birth. Other NINR-supported 
scientists identified pro- and anti-inflammatory biomarkers that 
predict how patients experience pain at different stages of breast 
cancer treatment, drawing a new link between pain and inflammation. 
Discoveries such as these pave the way for the development of 
personalized and effective treatments for adverse symptoms of illness.
                   self-management of chronic illness
    According to the Centers for Disease Control (CDC), chronic illness 
accounts for more than 75 percent of healthcare costs in the U.S., and 
often requires long-term management of illness among individuals, 
families, and healthcare providers. Learning how to manage chronic 
illness presents challenges to individuals of any age as well as their 
family members, from children remembering to bring their asthma 
medication with them to school to older adults maintaining daily 
activities as they face multiple chronic conditions, such as arthritis 
and heart disease. To address such challenges, NINR supports research 
that enables individuals with chronic illness and their caregivers to 
take an active role in understanding and managing their condition, and 
improving their quality of life. One current NINR-led initiative aims 
to equip families with effective strategies for improving self-
management of chronic illness in children and adolescents, enabling 
them to follow treatment regimens and make healthy lifestyle choices 
while still allowing ``kids to be kids.'' Another initiative emphasizes 
family-centered self-management that integrates family members as 
partners in care while promoting self-management for individuals of any 
age; this initiative has the potential to strengthen the ability of 
family members to work together to make treatment decisions, manage 
symptoms, and navigate the healthcare system. Through efforts like 
these, NINR's investment in self-management research contributes to 
helping people live active and healthy lives in the face of chronic 
illness.
           wellness: promoting health and preventing illness
    Another area of emphasis at NINR is on wellness research, which 
seeks to understand the physical, social, behavioral, and environmental 
causes of illness, identify healthy lifestyle behaviors, and develop 
interventions to promote health and prevent illness across the lifespan 
and in diverse communities. One study supported by NINR is refining and 
examining the effectiveness of a home-based sensor system for older 
adults, which monitors pulse, breathing, and restlessness while 
sleeping, and alerts healthcare providers to potential illness so that 
they can intervene early. Such warning systems may allow older adults 
to stay active and remain in their homes longer. In another project, 
researchers developed a teacher-delivered healthy lifestyles 
intervention that improved health behaviors and academic outcomes in 
high school adolescents. NINR also maintains its commitment to 
promoting wellness in vulnerable groups who are disproportionately 
affected by chronic illness. We currently lead an initiative to reduce 
health disparities in minority and underserved children through the 
development of culturally-appropriate, multifaceted interventions.
               enhancing end-of-life and palliative care
    Addressing the needs of patients with life-limiting illness through 
high-quality, effective end-of-life and palliative care continues to be 
a critical focus of NINR. As the lead NIH Institute for end-of-life 
research, NINR supports research to ease symptoms and support patients 
and their caregivers in coping with advanced illness, while also 
addressing the challenges of planning for end-of-life decisions. As an 
example, NINR-supported scientists recently found that pain continues 
to be underdiagnosed and undertreated for hospitalized patients at the 
end of life, suggesting that more work is needed to better understand 
the needs of individuals facing life-threatening illnesses. Recognizing 
that palliative care is a critical component of maintaining quality of 
life at any age and at any stage of illness, not just at the end of 
life, NINR supports initiatives to enhance palliative care. Given that 
a diagnosis of serious illness in a child is particularly difficult for 
families, NINR launched the Palliative Care: Conversations 
MatterTM campaign to raise awareness of pediatric palliative 
care and to provide evidence-based materials to help healthcare 
providers initiate often difficult conversations with pediatric 
patients and their families. NINR also continues to support a 
palliative care research cooperative to enhance the evidence base for 
palliative care interventions. A new NINR initiative to promote use of 
and long-term sustainability of the cooperative will encourage 
researchers across the country to capitalize on the existing resources 
and expertise and streamline the research process.
              looking toward the future: nurse scientists
    A primary goal of NINR is to prepare the next generation of nurse 
scientists to address health challenges and to contribute to an 
innovative, multidisciplinary, and diverse scientific workforce. NINR 
funds training and career development grants and programs to prepare 
nurse scientists to conduct research to build the scientific foundation 
for clinical practice. NINR's Summer Genetics Institute is an intensive 
training program on molecular genetics designed to improve research and 
clinical practice among graduate students and faculty. This year, our 
week-long Methodologies Boot Camp focuses on using Big Data in symptom 
research, and provides a research intensive program for participants to 
learn new state-of-the-art methodologies from nationally and 
internationally known scientists. By training nurse scientists to use 
new, innovative scientific methodologies, NINR advances nursing science 
to improve health.
    In closing, thank you for the opportunity to share with the 
Committee some of the ways the science we support impacts the health of 
the Nation. In fiscal year 2015, NINR will continue our mission to 
improve quality of life by advancing nursing science and by supporting 
research to inform high-quality and effective clinical care.
                                 ______
                                 
              Prepared Statement of Eric Green, M.D., Ph.D
    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2015 President's budget request for the National Human 
Genome Research Institute (NHGRI). The fiscal year 2015 budget of 
$498,451,000 reflects an increase of $1,323,000 above the enacted 
fiscal year 2014 level of $497,128,000.
    The research funded and conducted by NHGRI in fiscal year 2015 will 
continue to unlock the secrets of life's DNA code. We still have much 
to discover with regard to how the three billion DNA bases of the human 
genome influence our physical and biochemical characteristics--and, in 
turn, our health. While we continue to reveal all the information 
encoded by DNA, we have started pursuing clinical applications of 
genomic knowledge and implementing genomic medicine.
    Understanding how the structure and function of the human genome 
relates to health and disease will be essential for the implementation 
of genomic medicine. Among the knowledge to be gained is how the 
:20,000 genes in the human genome are turned on and off at the 
appropriate times and in the appropriate places; this is largely the 
role of regulatory elements within the genome that act like ``dimmer 
switches'' controlling lights. Through the Institute's Encyclopedia of 
DNA Elements (ENCODE) Project, a more detailed inventory of these 
regulatory elements is emerging. In fiscal year 2015, the Genomics of 
Gene Regulation (GGR) initiative will begin to investigate the 
choreography of these different elements in different cells and 
tissues. Many of the elements that ENCODE has identified and GGR will 
characterize play a role in human diseases and traits, underscoring the 
foundational value of these projects.
    More than 25 million Americans suffer from rare diseases, 
cumulatively more than those afflicted with cancer. While the genomic 
bases for just over 5,000 rare diseases have been established--the 
majority of those established since the end of the Human Genome 
Project--the causal genes for an estimated 2,000-4,000 additional rare 
diseases remain to be identified. To investigate the latter, NHGRI's 
Centers for Mendelian Genomics Program is harnessing powerful DNA-
sequencing technologies to analyze patients' genomes on an 
unprecedented scale en route to establishing the genomic underpinnings 
of these remaining rare disorders. The resulting discoveries offer the 
promise of ending the diagnostic odyssey of afflicted patients as well 
as insights about the diseases that may lead to new therapeutic 
approaches.
    In fiscal year 2015, NHGRI will also focus on more common, but more 
genomically complex, diseases--those diseases that reflect great public 
health burdens. One such disease, cancer, is fundamentally a disease of 
the genome. Hence, NHGRI has been collaborating with the National 
Cancer Institute in developing The Cancer Genome Atlas (TCGA) since 
2006, studying the genomes of different types of tumors and cataloging 
the discovered genomic aberrations. In fiscal year 2015, TCGA will 
reach the milestone of analyzing 10,000 tumor samples, revealing many 
new insights about cancer.
    Similarly, NHGRI has partnered with the National Institute on Aging 
to pursue the largest genomics study of Alzheimer's disease to date. 
The Alzheimer's Disease Sequencing Project (ADSP) is sequencing and 
analyzing the genomes of several hundred Alzheimer's patients to help 
identify the genomic factors contributing to this complex disease, 
which affects as many as 5 million Americans aged 65 and older.
    Investigators throughout the biomedical research enterprise--well 
beyond the study of genetic diseases--are now incorporating genomic 
analyses into their research. A major catalyst for this dissemination 
has been NHGRI's unparalleled Advanced DNA Sequencing Technology 
Program, the successes of which have led to a phenomenal drop in the 
cost of DNA sequencing,\1\ enabling many more investigators to 
incorporate genomic analyses into their research. However, these 
researchers have a widespread and urgent need for improved analytical 
tools for analyzing DNA sequence data. To address this, NHGRI has 
created the Genome Sequencing Informatics Tools (GS-IT) program. Like 
the Institute's development of cutting-edge innovations in DNA 
sequencing, GS-IT is creating pioneering robust data-analysis tools for 
studying genomes.
---------------------------------------------------------------------------
    \1\ Nature 507, 294-295 (20 March 2014) http://www.nature.com/news/
technology-the-1-000-genome-1.14901
---------------------------------------------------------------------------
    To become a reality, genomic medicine needs refined approaches for 
using genomic information to improve health outcomes. For instance, in 
fiscal year 2015, the Implementing Genomics Into Clinical Practice 
(IGNITE) Network will test methods for disseminating genomic medicine 
strategies more widely. IGNITE investigators will be initially studying 
the use of genomic risk information for treating kidney disease, the 
utility of family health history, and the use of genomic information 
for selecting appropriate medications. In another effort, NHGRI is 
partnering with the Eunice Kennedy Shriver National Institute of Child 
Health and Human Development to support the Newborn Sequencing in 
Genomic Medicine and Public Health (NSIGHT) Program, which is examining 
the potential for genome sequencing to improve the care of newborns.
    Pilot programs such as IGNITE and NSIGHT, in addition to other 
large genomics projects, are only valuable if the generated knowledge 
diffuses through the medical establishment. To help healthcare 
professionals become competent with genomic information in delivering 
patient care, NHGRI is working with the National Center for 
Biotechnology Information to develop the Clinical Genome Resource 
(ClinGen), which will provide a curated knowledgebase of clinically 
relevant genomic variants. ClinGen will be freely available to 
clinicians, researchers, and professional organizations developing 
clinical practice guidelines, helping to usher in larger-scale 
implementation of genomic medicine.
    To capitalize on the genomics research funded by NHGRI and other 
NIH institutes for medicine, the next generation of scientists and 
clinicians must be equipped with the skills to lead their fields during 
the 21st century. In fiscal year 2015, new institutional training 
programs and individual career awards in genomics research and in 
genomic medicine will develop leaders in those respective fields, 
including the provision of cross-training in associated disciplines 
such as bioethics and data science.
    Another of NHGRI's educational efforts targets the general public. 
The Institute collaborated with the Smithsonian Institution's National 
Museum of Natural History to create the exhibition Genome: Unlocking 
Life's Code. Privately funded, this widely acclaimed exhibition is 
expected to be visited by more than 3.5 million people before the end 
of fiscal year 2015. In addition, a series of nine public engagement 
programs are being produced; these events will remain accessible via 
the web to complement the exhibition as it travels North America over 
the next 5 years.
    As described above, NHGRI's genome sciences portfolio will continue 
to explain the role of the genome in human traits and disease, while 
its genomic medicine portfolio will apply that knowledge to improve 
human health. The Institute will ensure that information about genomic 
advances is disseminated to scientists and healthcare professionals as 
well as the general public, and that the technologies and generated 
knowledgebase will continue to be a growth engine for our economy.\2\
---------------------------------------------------------------------------
    \2\ http://www.unitedformedicalresearch.com/advocacy_reports/the-
impact-of-genomics-on-the-u-s-economy/
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                                 ______
                                 
             Prepared Statement of Alan E. Guttmacher, M.D.
    Mr. Chairman and Members of the Committee, I am pleased to present 
the fiscal year 2015 President's budget request for the Eunice Kennedy 
Shriver National Institute of Child Health and Human Development 
(NICHD) of $1,283,487,000. This reflects an increase of $2,657,000 over 
the fiscal year 2014 level of $1,280,830,000.
    Understanding human development, both normative and atypical, 
comprises the core of NICHD's mission. The Institute supports a broad 
range of research, conducted largely at academic institutions across 
the country, ranging from efforts to increase understanding of basic 
biological mechanisms to testing health interventions aimed at 
improving the lives of children, women, families, and those with 
disabilities. NICHD-supported research contributes to knowledge about 
our health, from the earliest stages through maturity.
                      pregnancy and birth outcomes
    Based on NICHD-supported research showing less than optimal health 
outcomes for infants born at 37 and 38 weeks of pregnancy (previously 
considered full-term), leading professional societies announced in the 
past year a new policy that pregnancy would now be considered full-term 
only after 39 weeks. This change should lead to improved standards of 
care and better health outcomes for mothers and infants.
    While previous studies had found that alcohol and illegal drug use 
during pregnancy frequently produce poorer infant health outcomes, a 
NICHD-funded network study has now provided evidence that smoking 
(including secondhand smoke), prescription painkillers, and illegal 
drugs used during pregnancy can double or triple the risk of 
stillbirth. These findings provide women and their clinicians important 
information about healthy behaviors in pregnancy.
    Through our Hunter Kelly Newborn Screening Research Program, NICHD 
has long provided the evidence base for determining whether a health 
condition can be detected in newborns, and whether it can be cured or 
treated. Currently, most states screen newborns for a panel of 29 
conditions, thus preventing extensive disease and disability. Now NICHD 
is partnering with the National Human Genome Research Institute on a 
major study to explore the possibilities for early diagnosis of a much 
larger number of disorders by sequencing newborns' genomes, while also 
exploring technical, clinical, and ethical questions raised by this new 
technology. Researchers also plan to develop a tool to help parents 
understand sequencing results, placing special emphasis on the needs of 
families from diverse cultures and their clinicians.
                  pediatric and adolescent development
    For many conditions, the earlier they are identified and treatment 
begun, the better the outcome. One of the goals of the NICHD-led 
National Children's Study is to amass an unprecedented amount of 
information about children's health, development, and environment to 
understand and improve health. Recently, researchers supported by NICHD 
have developed an updated screening tool, administered to parents, to 
help determine if a child between 18 months and 2 years old has autism, 
much earlier than the current average age of diagnosis of 4 years. 
Previous research has shown that earlier interventions can help improve 
developmental outcomes for children with autism. This tool is now 
widely available online, in 45 different languages.
    Since variations in nutrition and environment so heavily influence 
children's growth and development, NICHD engages in international 
studies to increase knowledge about optimal health in childhood. In 
some nutrient-deficient areas, children receive iron supplements to 
enhance development and prevent anemia; yet, recently, public health 
officials have become concerned that these supplements may increase 
children's risk for malaria. To test this theory, NICHD-supported 
researchers conducted a randomized clinical trial combining iron 
supplementation with prevention efforts (such as sleeping nets) in a 
malaria-prone area of Ghana, finding that the incidence of malaria was 
no higher for children who received the supplements than for those who 
did not, and assuring that beneficial iron supplementation could 
continue.
    Understanding human development in adolescence, with that period's 
substantial physical, mental, and behavioral changes, poses a 
particular challenge for researchers. While there is increased emphasis 
on encouraging young people to be physically active to reduce 
overweight and increase health, engaging in some physical activities 
may pose risks. Concerns have been raised about the potential long-term 
effects of repeated concussions in children, especially young athletes. 
Recently, NICHD partnered with other NIH ICs and the National Football 
League on eight research projects to help understand the effects of 
head injuries and improve the diagnosis of concussions. Although 
awareness is increasing that young people who may have had a concussion 
should not immediately return to play, these studies will help us 
understand the brain's healing process and what is required to prevent 
permanent damage to this vital organ, leading to such advances as more 
precise return to play policies.
    Parents of teenagers will not be surprised that adolescents often 
engage in risk-taking behaviors. They may, however, be surprised that 
informed parental supervision can have an impact on adolescent 
behaviors and even on potential injury or death. An intramural NICHD 
study on teen driving behaviors collected data from a nationally 
representative sample of 10th graders, finding that adolescents who 
reported being exposed to riding with an intoxicated driver in the 10th 
grade were considerably more likely to report driving while intoxicated 
in the 12th grade. The study indicates the importance of parents' not 
only monitoring their own children's driving behaviors, but also that 
of other young drivers with whom their children may be riding.
                             women's health
    One result of NICHD's 2012 ``Scientific Visioning'' process, which 
took a fresh look at what the Institute might accomplish across its 
broad mission over the next decade, was the establishment of the new 
extramural Gynecologic Health and Disease Branch. Researchers supported 
by the branch recently shed light on the relative success and safety of 
two surgical treatments for pelvic organ prolapse (a form of pelvic 
hernia). Previous research supported by NICHD suggested about 3 percent 
of U.S. women experience prolapse in a given year, most commonly older 
women and those who have given birth several times. The study found no 
statistically significant difference between the two types of surgery, 
providing critical information for surgeons and the 300,000 U.S. women 
who have this surgery each year.
                     individuals with special needs
    NICHD has long supported research on the causes and effects of 
intellectual and developmental disabilities, and on identifying 
effective therapies for these conditions. By working closely with 
leading researchers, clinicians, self-advocates, and families, 
Institute scientists identify the scientific resources most critical to 
ongoing progress on these conditions. In September 2013, NICHD, with 
the support of the NIH Down Syndrome Working Group and the Down 
Syndrome Consortium, launched DS-ConnectTM: The Down 
Syndrome Registry. DS-ConnectTM, which already includes over 
1,500 registrants, is a web-based, voluntary, secure health registry 
serving the Down syndrome community, providing anonymized information 
to families and clinicians, and facilitating connections between 
researchers and potential clinical research participants. In addition, 
the Down syndrome community recently provided extensive input on a 
revised NIH Research Plan on Down Syndrome, which will be available 
mid-2014.
    Another pressing need for scientists conducting research on 
cognition and brain disorders is the availability of sufficient brain 
tissue specimens. While NIH historically has funded investigator-
initiated, disease-specific brain banks, it is now taking a new 
approach to providing these scarce research resources by supporting a 
tissue-sharing collaboration among five brain banks. This new 
``NeuroBioBank'' will increase availability of biospecimens and 
establish a standardized resource for the research community.
                    embracing research opportunities
    Increasingly, biomedical and biobehavioral researchers need to work 
in transdisciplinary teams, manage massive amounts of data, and acquire 
new and diverse skill sets. For example, the medical rehabilitation 
needs of those with physical disabilities require a wide range of 
research, from improving our understanding of neurological repair to 
developing new generations of prostheses and assistive devices. In 
2012, a Blue Ribbon Panel made a series of recommendations to NICHD to 
bolster rehabilitation research at NICHD's National Center for Medical 
Rehabilitation Research (NCMRR) and across NIH. NICHD is implementing 
an innovative new operating model for NCMRR that is intended to greatly 
increase coordination of rehabilitation research among the many ICs 
that support it.
    NICHD is excited to launch the Human Placenta Project, a 
coordinated international initiative to understand in real time the 
structure and function of the human placenta, arguably the least 
understood human organ. The placenta is not only critical for both 
maternal and fetal health, but also has substantial implications for 
conditions that arise later in life in both the mother and child, such 
as cardiovascular disease. The Project's goals include understanding 
placental development in normal and abnormal pregnancies, developing 
biomarkers to help predict adverse pregnancy outcomes, and developing 
interventions to prevent abnormal placental and fetal development. The 
currently projected span of the project is a decade, beginning with a 
workshop in May 2014 to develop a research plan.
    Thank you for the opportunity to submit some of NICHD's 
accomplishments over the last year and a few of its many exciting plans 
for the immediate future.
                                 ______
                                 
              Prepared Statement of Richard J. Hodes, M.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2015 budget request for the National 
Institute on Aging (NIA) of the National Institutes of Health (NIH). 
The fiscal year 2015 budget includes $1,170,880,000, which is 
$1,453,000 more than the comparable fiscal year 2014 level of 
$1,169,427,000.
    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 retirement age and 
beyond, profound changes will occur in our economic, healthcare, and 
social systems.
    The NIA leads the national effort to understand aging and to 
develop interventions that will help older adults enjoy robust health 
and independence, 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 support training of the next generation of researchers.
              understanding aging at its most basic level
    NIA-supported studies in the emerging field of geroscience, which 
explores the basic mechanisms underlying age-related changes, including 
those which could lead to increased disease susceptibility, will 
provide needed insight into ways to address aging-related diseases and 
disorders. The NIA-led NIH GeroScience Interest Group (GSIG) involves 
active participation by 20 NIH Institutes and is leading the effort to 
accelerate and coordinate efforts to promote further discoveries on the 
common risks and mechanisms behind age-related diseases and conditions. 
In October 2013, the GSIG and private-sector partners convened a 
national Summit, ``Advances in Geroscience: Impact on Healthspan and 
Chronic Disease,'' which drew more than 500 expert participants from 
around the world. We expect its outcomes to further energize this 
field.
    An increasingly important research area is the identification of 
genes and gene variants related to aging and age-related disease. Such 
research will be accelerated by the addition of data on more than 
78,000 older individuals from one of the Nation's largest and most 
diverse genomics projects, Genetic Epidemiology Research on Aging, to 
the NIH database of Genotypes and Phenotypes (dbGAP). These data will 
be widely available to qualified investigators.
         improving the health and well-being of older americans
    NIH-supported investigators are testing 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 70; testosterone supplementation to delay or prevent frailty in 
older men; exercise for mood, health, and cognition; and an array of 
interventions for menopausal symptoms.
    NIA also supports research aimed at development of interventions 
that will enable older adults to remain independent for as long as 
possible. For example, researchers used data from nine large NIA-funded 
studies to develop diagnostic criteria for low muscle mass and 
weakness. These conditions lead to disability in older people, but are 
rarely recognized as clinical problems by healthcare providers. This 
work is a milestone toward the development of new diagnostic and 
treatment strategies for this common and disabling condition. In 
addition, the recent NIA-supported finding that training to improve 
cognitive abilities in healthy older people lasts to some degree for 10 
years after the training program was completed provides an important 
piece of evidence that cognitive health can be improved and maintained 
into older age.
    Serious injuries from falls, such as broken bones or traumatic 
brain injury, are a major reason for the loss of independence among 
older people. In 2013, NIA and the Patient-Centered Outcomes Research 
Initiative (PCORI) solicited applications for funding to conduct a 
randomized clinical trial of a multifactorial strategy for preventing 
serious fall-related injuries among non-institutionalized older people. 
The trial will begin in 2014.
    NIA is also a leader in the trans-NIH Science of Behavior Change 
initiative. We are hoping that the long-term outcome of this initiative 
will be to enhance the efficacy of interventions to help individuals 
make and maintain positive changes in their health behaviors. As an 
example, one NIA-managed study in this initiative has shed light on how 
stress can reduce or eliminate the ability of individuals to benefit 
from training designed to help them regulate their emotions and better 
control their behavior, suggesting possible changes to our behavioral 
intervention strategies.
    Because investigators often, for a variety of reasons, have 
difficulty recruiting older people into clinical research studies, NIA 
is collaborating with the Administration for Community Living, the 
Centers for Disease Control and Prevention, state and community-based 
health and social service providers, researchers, and private 
organizations on the Recruiting Older Adults into Research (ROAR) 
project.
             building momentum against alzheimer's disease
    NIA is the lead Federal agency supporting research on Alzheimer's 
disease (AD), which despite our best efforts continues to be a serious 
public health issue that directly affects as many as 5 million 
Americans. In fiscal year 2014, NIA received approximately $100 million 
in additional appropriated funds. We plan to use these additional funds 
to support Alzheimer's research in areas of strategic priority, funding 
additional awards to applications received from Funding Opportunity 
Announcements issued in fiscal year 2013-fiscal year 2014. We will 
continue to be guided by the strategic goals outlined in the National 
Action Plan on Alzheimer's Disease and the results from the 2012 
Alzheimer's Disease Summit. A second Summit is planned for February 
2015 to update milestones and stimulate further research.
    Recent findings have expanded our understanding of AD and provided 
insights into prevention and treatment of the disease. For example, 
NIA-funded researchers recently identified a molecule called REST, 
which is lost in the brains of patients with Alzheimer's disease, and 
whose deletion in mice leads to neurodegeneration. REST represents a 
novel potential target for intervention into the disease. Investigators 
have also found that conjugated equine estrogens, the most common type 
of postmenopausal hormone therapy in the United States, has no long-
term risk or benefit to cognitive function in younger postmenopausal 
women, aged 50-55. The earlier Women's Health Initiative Memory Study 
linked the same type of hormone therapy to cognitive decline and 
dementia in older postmenopausal women, but this finding suggests that 
women taking certain estrogen-based hormone therapies in their early 
postmenopausal years may not be at increased risk for eventual 
cognitive decline.
         empowering the next generation of researchers in aging
    As the number of older Americans continues to grow, we must not 
only increase the number of practicing physicians trained in geriatrics 
and relevant subspecialties but also foster the development of the next 
generation of physician-scientists whose clinical research will lead to 
improved care and more effective treatment options for older patients 
with complex medical conditions. Two ongoing programs--Grants for Early 
Medical/Surgical Subspecialists' Transition to Aging Research 
(GEMSSTAR), supporting physicians who seek to become clinician-
scientists in geriatric aspects of their subspecialty, and Medical 
Students Training in Aging Research (MSTAR), targeting first-year 
medical students in order to stimulate early interest in an aging 
research career--remain highly successful. Building on new technologies 
that enable us to reach a wide audience efficiently and inexpensively, 
we have initiated a series of Technical Assistance webinars to provide 
participants, particularly those with an interest in health disparities 
research, with guidance on navigating the NIA grants application 
process. Finally, the Butler-Williams Scholars Program (formerly the 
NIA Summer Institute) remains a vibrant and vital institution at NIA, 
drawing a record number of applications for the 2014 session.
                                 ______
                                 
           Prepared Statement of Stephen I. Katz, M.D., Ph.D.
    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 2015 NIAMS budget of 
$520.189 million includes an increase of $0.851 million over the 
comparable fiscal year 2014 level of $519.338 million.
    The NIAMS supports a broad range of research, training, and 
information dissemination activities. Many of the conditions within the 
NIAMS mission are very common while some are rare, affecting only a few 
thousand people world-wide. All have a major impact on the quality of 
people's lives. Diseases addressed by NIAMS affect individuals of all 
ages and of all racial and ethnic backgrounds; many disproportionately 
affect women and minorities. Over the years, NIAMS-funded research 
teams have made significant progress in uncovering the causes of and 
improving the treatments for many disorders of the bones, muscles, 
joints, and skin.
    While many treatments for arthritis and musculoskeletal and skin 
conditions have their origins in NIH-supported basic research, the 
timeframes for translating fundamental knowledge into therapies remain 
unacceptably long, and too many potential therapies fail late in 
development. To improve the drug development process, NIAMS has 
partnered with industry, non-profit groups, and other government 
agencies for the NIH Accelerating Medicines Partnership program in 
lupus and rheumatoid arthritis (RA). Through the program, a network of 
investigators will use advanced tools and techniques to analyze blood 
and tissue samples from patients. The overall goals are to gain 
insights into lupus and RA biology, improve the selection of biological 
targets for drug development, and ultimately produce new therapies.
    The advent of technologies for collecting and analyzing large 
amounts of data corresponds with an increasing appreciation of the 
interactions that occur among different tissues and organ systems, and 
with the microorganisms inside our body or on our skin. When 
researchers compared the gut microbes of people who had newly 
diagnosed, untreated RA with those found in the digestive tracts of 
healthy people, patients with RA who were receiving treatment, and 
psoriatic arthritis patients, they found that the bacterium Prevotella 
copri (P. copri) was more abundant in patients with new-onset RA than 
in the other groups. If additional studies determine that altered 
levels of P. copri contribute to RA, therapies that target the 
bacterium could help to prevent the disease or delay its onset. 
Similarly, another group of researchers recently demonstrated that 
Staphylococcus aureus colonies on the skin of people who have atopic 
dermatitis, or eczema, release a toxin that causes skin inflammation. 
This finding provides an impetus for further studies into whether 
blocking the toxin could help people who are susceptible to atopic 
dermatitis.
    Other research is uncovering complex connections between the immune 
system and skeletal health, and the role of hormones produced by bone 
on the development and function of the nervous system. Recent findings 
have linked the misfolding of a protein that helps immune cells 
recognize and destroy invading bacteria or viruses to the bone erosion 
that characterizes spondyloarthritis of the spine. Other research has 
revealed that the bone-derived hormone osteocalcin is capable of 
interacting with neurons in the brain and influencing brain structure 
and behavior, at least in mice.
    Many people think of broken bones as a normal part of an active, 
healthy childhood. Although any bone will break if enough force is 
applied to it, researchers are learning that the bones of some children 
and teens have structural deficits that can be readily identified based 
on what the patient was doing when the bone was broken. Children who 
broke an arm because of moderate impact, as would occur when falling 
off a bicycle, had bones that resembled their uninjured peers; but, 
those whose forearm bones broke upon mild impact (e.g., a fall during a 
minor playground scuffle) showed signs of compromised bone strength and 
bone quality. While we do not know the extent to which bone weakness 
during childhood predisposes people to osteoporosis and fragility 
fractures later in life, this study is the first to suggest that a 
simple screening question could identify the young people who might 
benefit most from dietary changes and activities to improve bone 
health.
    NIAMS also is involved in efforts to identify laboratory-based or 
imaging biomarkers that will guide treatment development or will 
improve patient care. Activities include the Foundation for the NIH 
(FNIH) Biomarkers Consortium project to evaluate biochemical and 
imaging biomarkers for more precise ways of measuring osteoarthritis 
progression during clinical trials; this project builds on resources 
created by the Osteoarthritis Initiative (OAI), a public-private 
partnership spearheaded by NIAMS and the National Institute on Aging 
with support from other NIH components, the U.S. Food and Drug 
Administration, the FNIH, and private sponsors. A separate research 
team, focused on molecular changes associated with scleroderma, 
recently reported that blood levels of a protein appeared to 
distinguish between patients who were likely to develop life-
threatening lung complications that require aggressive treatments and 
those whose disease would not warrant risky therapies. Investigators 
are confirming their observations as a next step before the findings 
are applied clinically.
    Additional research into disease-associated genetic defects and 
molecular pathways is pointing to new uses for drugs that have been 
approved for other conditions. Work by investigators studying a group 
of muscle diseases called the disferlinopathies--which includes limb-
girdle muscular dystrophy type 2B--suggests that calcium channel 
blocking drugs might reduce some of the tissue damage that accumulates 
as the diseases progress. Another example comes from a team that 
identified 42 areas in the human genome that are associated with RA; 
many of the gene products are already targeted by existing drugs. These 
potential drug repurposing opportunities will be explored more 
thoroughly before clinical trials can begin in patients.
    Once results from clinical studies are available, many healthcare 
providers insist that findings be validated before changing how they 
practice medicine. The ability to verify conclusions is equally 
important at the basic and preclinical levels of research, particularly 
when results become the basis for clinical trials. In fiscal year 2015, 
NIAMS plans to refocus the Pilot and Feasibility Clinical Research 
Grants in Arthritis and Musculoskeletal and Skin Diseases program--a 
grant mechanism to foster early-stage clinical trials on which larger, 
more robust studies will be based--to emphasize the need for a strong 
scientific premise on which a proposed project is based.
    NIAMS is committed to ensuring that well-trained basic scientists 
and clinical researchers are prepared to conduct cutting-edge studies 
related to rheumatic, musculoskeletal, and skin diseases. The Institute 
awards a combination of institutional training grants and individual 
fellowships for this purpose. NIAMS has expanded its participation in 
NIH training programs for fiscal year 2015 to include the Ruth L. 
Kirschstein National Research Service Awards for Individual Predoctoral 
MD/PhD and Other Dual Doctoral Degree Fellows (F30) program. The 
Institute also has begun meeting with clinical or patient-oriented 
research career development awardees--both early in their award and as 
they are about to transition to independent careers--to identify 
challenges that they face and ways to better support them and future 
awardees.
    As part of a commitment to communicating about NIAMS programs and 
research results, NIAMS has enhanced its outreach to patients, 
healthcare and research professionals, and the general public via 
social media and other activities. Building on a successful 2013 effort 
to ensure that the results of NIH research investments and health 
messages reach all Americans, NIAMS again partnered with other 
components of the Department of Health and Human Services and with 
patient advocacy groups to create a new set of health planners, titled 
A Year of Health, A Guide to a Healthy 2014 for You and Your Family. In 
the past 2 years, NIAMS received requests for these health planners 
from all 50 states and five U.S. territories, demonstrating a robust 
need for credible, research-based health information in African 
American, American Indian/Alaska Native/Native Hawaiian, Asian 
American/Pacific Islander, and Hispanic/Latino communities.
    Looking to the future, we are updating the Institute's Long-Range 
Plan. As with the fiscal year 2010-2014 plan, the new document will 
inform the Institute's priority setting process while enabling the 
NIAMS to adapt to the rapidly changing biomedical and behavioral 
science landscapes. When complete, the plan will outline the 
Institute's perspective on research needs and opportunities within the 
NIAMS mission, and will serve as a resource for all who are interested 
in our activities.
                                 ______
                                 
                Prepared Statement of George Koob, Ph.D.
    Mr. Chairman and Members of the Committee: As the new Director of 
the National Institute on Alcohol Abuse and Alcoholism (NIAAA) of the 
National Institutes of Health (NIH), I am pleased to present the 
President's budget request for the Institute. The fiscal year 2015 
NIAAA budget request of $446,017,000 reflects an increase of $606,000 
over the comparable fiscal year 2014 enacted level of $445,411,000.
                          scope of the problem
    Excessive alcohol use has profound effects on individuals, families 
and communities; and the Centers for Disease Control and Prevention 
(CDC) estimates that excessive alcohol consumption cost the U.S. $224 
billion in 2006. In 2012, nearly one quarter of the U.S. population 
aged 21 and older and over 15 percent of young people ages 12-20 
reported binge drinking (i.e. consuming five or more drinks on a single 
occasion) at least once in the past month, according to the Substance 
Abuse and Mental Health Services Administration (SAMHSA). Binge 
drinking has serious acute and long term consequences--both for youth 
and adults. NIAAA estimates that 18 million Americans have an alcohol 
use disorder (AUD) and NIAAA research has established an important 
connection between early alcohol use and the development and severity 
of AUD. Of those who meet the criteria for an AUD, only about 15 
percent ever seek treatment.
                             niaaa research
    To reduce the considerable burden of illness and the societal costs 
associated with alcohol misuse, NIAAA is working to advance evidence-
based prevention and treatment for alcohol problems for individuals at 
all stages of life, including those with co-occurring disorders. 
NIAAA's research portfolio is broad, ranging from studies on the 
underlying biological mechanisms that drive excessive drinking and the 
development of medications for AUD targeting these mechanisms, to 
studies on policies and interventions designed to reduce harm both to 
drinkers and those around them. NIAAA's portfolio also includes both 
research on the health benefits associated with moderate drinking and 
on the consequences of alcohol misuse, including fetal alcohol spectrum 
disorders (FASD), alcohol effects on the developing adolescent brain, 
and alcohol effects on tissue and organ damage.
    NIAAA's cutting edge work in the neuroscience of alcohol effects on 
the brain provides not only a firm foundation for development of novel 
treatments for AUD but also a framework for prevention. The NIAAA 
portfolio focuses on the neurocircuitry changes that promote the 
development of AUD as well as those that convey resilience. 
Particularly critical are the studies of the adolescent brain and how 
excessive alcohol intake can delay, or permanently compromise normal 
development of the brain's executive and self-regulatory functions.
    A key goal of NIAAA is to work with other NIH Institutes and 
Centers and Federal agencies to enhance integration of research on the 
abuse of alcohol and other substances. Notably, NIAAA co-leads the 
Collaborative Research on Addictions at NIH (CRAN) with the National 
Institute on Drug Abuse (NIDA) and the National Cancer Institute (NCI); 
co-chairs the Alcohol Policy and Underage Drinking Subcommittee of the 
HHS Behavioral Health Coordinating Council with the CDC; and 
collaborates with the National Institute of Mental Health (NIMH), NIDA, 
Department of Defense (DOD) and the Veterans Administration (VA) on the 
implementation of the National Research Action Plan for Improving 
Access to Mental Health Services for Veterans, Service Members, and 
Military Families.
    Recognizing that medications currently available to treat AUD can 
be highly effective but do not work for everyone, NIAAA continues to 
make significant progress towards developing additional evidence based 
pharmacotherapies. NIAAA's Clinical Investigations Group (NCIG), 
established to rapidly test candidate compounds (within 12-18 months), 
is streamlining the medications development process for AUD. NCIG 
recently completed a multisite clinical trial that showed the anti-
smoking medication varenicline (Chantix) significantly reduced alcohol 
consumption and craving in both smokers and non-smokers with AUD. Going 
forward, NCIG will test both repurposed and novel compounds often 
working in collaboration with extramural scientists and the 
pharmaceutical industry. NIAAA also supports promising pharmacotherapy 
research outside of NCIG. In an independent study, the widely 
prescribed anti-seizure medication gabapentin, used to treat pain and 
used off-label for migraines, reduced heavy drinking and other related 
symptoms in alcohol dependent patients. A study to replicate the 
gabapentin finding within NCIG is anticipated. It is important to note 
that currently available medications are very effective for many, and 
that NIAAA is working to make clinicians and the public aware of the 
range of available treatment options for AUD, as well as promoting 
research into more effective implementation of treatment.
    Given that AUD often co-occurs with other substance use and/or 
mental health disorders, major priorities of the Institute are to 
understand the complex relationships between and develop effective 
treatments for alcohol misuse and co-occurring disorders. For example, 
AUD frequently co-occurs with post-traumatic stress disorder (PTSD), 
thereby complicating treatment for both conditions. PTSD is prevalent 
among military personnel and veterans, and also among individuals who 
have experienced sexual assault--a far too common occurrence on college 
campuses, and one often associated with excessive drinking by both 
perpetrators and victims. PTSD increases risk for AUD; conversely, 
chronic alcohol use may increase the risk for PTSD by altering the 
brain's ability to recover from a traumatic experience. Using an animal 
model of PTSD, NIAAA intramural researchers discovered that chronic 
alcohol exposure altered neurons in the medial prefrontal cortex region 
of the brain, making the animals slower to suppress a conditioned fear 
response. Differences in the ability to handle fear responses could 
help explain differences in vulnerability to PTSD among humans, and 
lead to new therapeutic approaches and diagnostic risk biomarkers. 
NIAAA also supports other promising studies on co-occurring PTSD and 
AUD.
    The consequences of binge drinking for all ages range from acute, 
e.g. injuries and blackouts, to long term, e.g. severe AUD and organ 
damage. Recent results of NIAAA-supported research have revealed that 
binge drinking may be harmful in more ways than previously thought. For 
example, in results published this year, a single episode of binge 
drinking (which in the study raised the blood alcohol concentration to 
0.08 g/dL, the legal limit for driving while intoxicated, within 60 
minutes) increased leakage of bacterial endotoxins from the gut into 
the bloodstream and elicited an immune response, demonstrating that 
binge drinking produces acute damage in the body, even in healthy 
people. Notably, women had higher blood alcohol levels and circulating 
endotoxin levels than men. Often viewed as a rite of passage, binge 
drinking is pervasive among our Nations' youth with 1.7 million young 
people ages 12-20 engaging in this behavior five or more times per 
month according to SAMHSA. NIAAA's current studies on the effects of 
alcohol on the developing brain will inform a more extensive study 
under CRAN to assess the effects of drugs and alcohol, alone and in 
combination, on the adolescent brain. College and University Presidents 
are especially concerned about the rampant heavy use of alcohol among 
their students resulting in an estimated 1,825 deaths, 696,000 
assaults, and 97,000 sexual assaults annually. NIAAA will soon release 
a decision tool to help college administrators select effective 
evidence-based interventions appropriate for their campuses. NIAAA also 
promotes screening and brief intervention (SBI) for youth, and launched 
an online course with Medscape to provide continuing medical education 
for healthcare professionals to help them conduct fast, evidence-based 
alcohol SBI with youth. To date, over 14,000 healthcare providers have 
been Medscape certified.
    Preventing, diagnosing, and treating alcoholic liver disease (ALD) 
is also a major priority. NIAAA funds four research consortia to pursue 
new clinical approaches to treat alcoholic hepatitis, a severe form of 
ALD. NIAAA will also continue to pursue biomarkers of liver injury to 
facilitate earlier diagnosis.
    NIAAA has significantly advanced our understanding of the health 
and social impacts of alcohol use and misuse. NIAAA will continue to 
pursue opportunities leading to better outcomes for alcohol-related 
problems, and support a diverse biomedical research workforce that is 
equipped to tackle these public health challenges.
                                 ______
                                 
            Prepared Statement of Donald A.B. Lindberg, M.D.
    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 2015 
budget of $372,851,000 includes an increase of $5,628,000 over the 
comparable fiscal year 2014 level of $367,223,000.
    The National Library of Medicine, the world's largest biomedical 
library, builds and provides electronic information resources used 
billions of times each year by millions of scientists, health 
professionals and members of the public. Many health information 
searches that are initiated on the Internet actually retrieve 
information from an NLM Web site. NLM is crucial in the dissemination 
of biomedical research results--DNA sequences, clinical trials data, 
toxicology and environmental health data, research publications, and 
consumer health information to scientists, health professionals, and 
the public. A leader in biomedical informatics and information 
technology, NLM also supports and conducts research, development, and 
training in biomedical informatics, data science, and health 
information technology; and coordinates the 6,100-member National 
Network of Libraries of Medicine that promotes and provides access to 
health information in communities across the United States.
    NLM's programs and services directly support NIH's key initiatives 
in basic research, precision medicine, research training, as well as in 
data science and Big Data. NLM's National Center for Biotechnology 
Information (NCBI) is a focal point for ``Big Data'' in biomedicine and 
a leader in organizing and providing rapid access to massive amounts of 
genetic sequence data generated from evolving high-throughput 
sequencing technologies. NCBI serves more than 30 terabytes of 
biomedical data to more than 3.3 million users daily. Some of the 
largest datasets, such as those from NIH's 1000 Genomes Project, are 
also available in the Amazon cloud. This allows faster access and 
analysis by researchers who may be otherwise hampered by insufficient 
bandwidth or computing power. Additionally, the Library organizes and 
provides access to the published medical literature; 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, making published NIH-
funded research freely and permanently available to the public. NLM/
NCBI databases are cited in laws and Congressional legislation (e.g., 
Public Law 110-161,Consolidated Appropriations Act and HR 4186, the 
Frontiers in Innovation, Research, Science, and Technology) as a model 
for facilitating public access to federally funded data and 
publications.
    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.
               biomedical and health information services
    NLM's PubMed/MEDLINE database is the world's gateway to research 
results published in the biomedical literature. It links 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. PubMed contains more 
than 23 million references to articles in the biomedical and life 
sciences journals providing high quality information to about 2.3 
million users per day. 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. 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 160,000 
clinical studies with sites in 185 countries and summary results for 
more than 11,000 trials, including many results that are not available 
elsewhere.
                standards for electronic health records
    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 electronic 
health record (EHR) products and personal health record tools. EHRs 
with advanced decision-support capabilities and connections to relevant 
health information are essential to improving healthcare and helping 
Americans manage their own health. 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.
                   health information for the public
    The NLM has a wide range of outreach programs to enhance awareness 
of NLM's diverse information services among biomedical researchers, 
health professionals, librarians, patients, and the public. To improve 
access to high quality health information, NLM works with the 6,100 
institutions of the National Network of Libraries of Medicine, a 
network of academic health sciences libraries, hospital libraries, 
public libraries, and community-based organizations and has formal 
partnerships with tribal colleges and other minority serving 
institutions. In fiscal year 2013, dozens of community-based projects 
were funded across the country to enhance awareness and access to 
health information, including in disaster and emergency situations, and 
to address health literacy issues.
    The Library's MedlinePlus Web site provides integrated access to 
high quality consumer health information produced by all NIH components 
and HHS 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 print and online 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 print magazine reaches a readership of up to 5 million 
nationwide and the online version reaches millions more. Each issue 
focuses on the latest research results, clinical trials and guidelines 
from the 27 NIH Institutes and Centers.
    The Library diversifies access to all its information resources, 
through mobile devices and ``apps.'' NLM continues to be a leading 
player in social media amongst HHS agencies with active Facebook, 
Twitter, and You Tube accounts, including the very popular @medlineplus 
Twitter feed and a Spanish-language counterpart, several online 
newsletters, and its National Network of Libraries of Medicine, which 
covers the United States and hosts eight Facebook pages, 10 Twitter 
feeds and 12 blogs. NLM is consistently ranked among the most liked, 
most followed, and most mentioned organizations amongst small 
government agencies with social media accounts.
    In conclusion, the Library is a trustworthy source of health 
information for the public and vital to the practice of 21st century 
medicine and the progress of science. 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 Jon R. Lorsch, PH.D.
    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 2015 budget of $2,368,877,000 includes an increase of $6,983,000 
above the comparable fiscal year 2014 level of $2,361,894,000. NIGMS 
considers its public funds a precious resource and focuses on 
efficiency and effectiveness in making investments in research and 
training. The Institute spends 97 percent of its budget outside of the 
NIH, funding biomedical research and training at universities and other 
institutions across the country--where creative minds are at work every 
day producing new knowledge about health and disease.
    Scientific discovery is the engine for advances in medicine, as 
research results lead to new treatments and refine current standards of 
care. Biomedical research relies on attracting and retaining a creative 
and well-trained workforce. NIGMS remains committed to enabling 
researchers throughout the United States to answer important scientific 
questions in fields such as cell biology, biophysics, genetics, 
developmental biology, pharmacology, physiology, biological chemistry, 
biomedical technology, bioinformatics, computational biology, selected 
aspects of the behavioral sciences and specific cross-cutting clinical 
areas that affect multiple organ systems. To assure the vitality and 
continued productivity of the research enterprise, NIGMS also provides 
leadership in training the next generation of scientists as well as in 
developing and increasing the diversity of the scientific workforce.
                             back to basics
    The high value of investigator-initiated research has stood the 
test of time. This approach, in which scientists decide what questions 
are important to study, ultimately leads to major advances in medicine 
and technology. Examples include:
  --Studies of virus-resistant bacteria led to the discovery of 
        restriction enzymes, which act like highly specific scissors 
        for cutting DNA. This discovery launched the multi-billion-
        dollar biotechnology industry, starting with the laboratory-
        based production of life-saving medicines like insulin and now 
        extending even beyond biomedicine into agriculture and 
        biofuels.
  --Seemingly esoteric studies of how electric fields affect DNA 
        replication in bacteria lead directly to the discovery of the 
        anti-cancer drug cisplatin, which has saved thousands of human 
        lives.
  --Studies of enzymes that copy DNA and RNA and that cut proteins 
        enabled the development of drugs to treat HIV infection.
    To ensure a continued pipeline of fundamental scientific advances 
that will lead to future medical and technological breakthroughs, NIGMS 
is rebalancing its portfolio to renew and reinvigorate its support for 
question-driven, investigator-initiated research. This rebalancing has 
received strong support from stakeholder organizations, including the 
Federation of American Societies for Experimental Biology, an umbrella 
group representing 26 scientific societies and over 115, 000 
researchers.
                   planning carefully for the future
    NIGMS has begun a new strategic planning process that is focusing 
on enhancing the efficacy, efficiency, and adaptability of the 
Institute's internal processes and the mechanisms through which we 
support biomedical research. In particular, we are exploring the 
development of new grant mechanisms that would increase stability and 
flexibility for researchers and maximize the scientific return on 
taxpayers' investment. These mechanisms will focus on the efficient use 
of funds, encouraging scientists to undertake ambitious and creative 
projects that may be the breakthroughs of tomorrow.
    NIGMS is also developing new strategies to strengthen and maintain 
the pipeline of talented, creative, diverse and highly skilled young 
investigators. This segment of the biomedical workforce is essential 
for the future of scientific research in the United States, which is in 
turn essential for the future health and economic competitiveness of 
our Nation. Specific strategies we are considering to address the 
challenges facing young investigators include outcomes-based 
enhancements of our training programs and efforts to improve the 
competitiveness of young investigators in obtaining and keeping 
research grants.
                    supporting a diversity of ideas
    NIGMS is proud to be the home of the IDeA program, which ensures 
that cutting-edge research is conducted in every region of the country. 
This strategy is critical to the strength of our biomedical research 
enterprise, as it meets the need to involve the most diverse set of 
minds, experiences and approaches for solving difficult health-related 
problems. Last year, NIGMS funded or co-funded 58 competing grants to 
IDeA researchers, this included 25 competing Centers of Biomedical 
Research Excellence awards. Particularly exciting research developments 
funded by the IDeA program include the demonstration by Kentucky 
researchers that electrical stimulation of the spinal cord can restore 
some motor function in individuals with paraplegia; a study by 
scientists in South Carolina showing that nanoparticles coated with 
antioxidant proteins can protect against stroke-related damage; and a 
neonatal telemedicine center in Arkansas that has contributed to a 
significant decrease in statewide infant mortality.
    As requested by both the House and Senate and required by the 
Consolidated Appropriations Act of 2014, NIH has submitted a response 
to the National Academies' Report on EPSCoR and related programs. As 
part of the NIGMS strategic planning process, we are developing plans 
for enhancing access to resources for moving discoveries and innovative 
ideas from laboratories in IDeA states into commercial products. In 
particular, we are exploring support for regional biotechnology 
incubators that would give faculty in IDeA states access to laboratory 
space, equipment, expertise, and advice required to make their work 
competitive for SBIR/STTR and venture capital funding.
                   advancing health through discovery
    This past year, NIGMS-funded scientists broke new ground in a range 
of areas relevant to health, including chemistry, microbe-host 
interactions, computer modeling, and metabolism. Selected examples 
include:
  --A Tennessee researcher developed a chemical method to shave the 
        cost of manufacturing expensive drugs, including those used to 
        treat HIV/AIDS. The method is also environmentally friendly in 
        that it employs natural molecules called enzymes instead of 
        synthetic chemicals that are often hazardous.
  --A scientist from Vermont created the first-ever interaction map of 
        human proteins that attach to proteins from arenavirus and 
        hantavirus, providing potential new targets for therapies to 
        treat the often deadly illnesses caused by these classes of 
        viruses.
  --A Pennsylvania researcher found compounds that block a recently 
        discovered pathway for preventing production of damaged 
        proteins. These chemicals have antibiotic activity, suggesting 
        they might eventually be developed into a new class of 
        antibacterial drugs.
  --A scientist from California learned from mouse studies that a high-
        fat diet influences the internal body clock controlling liver 
        metabolism. The team also discovered that the effect was 
        reversible by returning to a balanced, low-fat diet.
    These discoveries are a small subset of the productivity of the 
nearly 4,000 scientists NIGMS supports throughout the United States. 
Our public investment to fuel their curiosity-driven exploration of 
biomedicine is growing knowledge, and local economies, as well as 
improving the health of all Americans.
    Thank you, Mr. Chairman. I would be pleased to answer any questions 
that the Committee may have.
                                 ______
                                 
             Prepared Statement of Yvonne T. Maddox, Ph.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget for the National Institute on Minority Health 
and Health Disparities (NIMHD) of the National Institutes of Health 
(NIH). The fiscal year 2015 budget of $267,953,000 is the same as the 
fiscal year 2014 enacted level of $267,953,000.
                              introduction
    As the primary Federal agency for leading, coordinating and 
facilitating research to improve minority health and eliminate health 
disparities, NIMHD impacts the lives of millions of Americans burdened 
by disparities in health status and healthcare delivery, including 
racial and ethnic minority groups as well as rural and low-income 
populations. A population is a health disparity population if it is 
determined that there is a significant disparity in the overall rate of 
disease incidence, prevalence, morbidity, mortality, or survival rates 
in the population as compared to the health status of the general 
population. The elimination of health disparities requires a 
multidisciplinary approach, with collaboration, coordination, and 
integration across NIH Institutes and Centers (ICs), other Federal 
agencies and private-sector organizations to fully understand and solve 
the underlying biological and non-biological causes of health 
disparities.
                   fundamentals of health disparities
    In order to understand the social, behavioral, biological, and 
environmental factors influencing health disparities, NIMHD is studying 
the fundamental causes of diseases and conditions that 
disproportionately affect individuals from health disparity 
backgrounds. For example, one project studies the higher incidence and 
mortality of breast cancer in African American women through research 
that examines the role genetic differences in the tumor suppressor 
protein, p53, plays in the disparity. Researchers hypothesize that some 
racial/ethnic groups have disproportionate p53 variants that may 
contribute to breast cancer health disparities in the age of onset, 
incidence, and lack of pregnancy protection in African American women. 
Another study takes knowledge about causal pathways learned at the 
bench and extends the findings to social, behavioral, health services 
and/or policy approaches to test ways to improve minority health and 
eliminate health disparities. This project examined unconscious 
stereotyping of Hispanic patients among medical and nursing students. 
The study found that students endorsed stereotypes that Hispanic 
patients would be non-compliant or likely to engage in high-risk health 
behaviors, even if the students reported trying consciously to avoid 
biased thinking. This unconscious bias of medical providers can be one 
factor in the disparity in healthcare delivery faced by minority 
patients.
                    collaborative research framework
    Comprehensively addressing health disparities requires a 
transdisciplinary framework that fosters an integrated approach 
involving biology, behavioral and social sciences, environmental 
science, public health, healthcare delivery, economics, public policy, 
and many other disciplines. It also requires strong collaborations 
between researchers and community organizations, service providers and 
systems, government agencies, and other stakeholders to ensure that 
contextually appropriate and relevant research is conducted, and that 
findings can translate into sustainable individual, community, and 
systems level changes that improve the health of the U.S. population. 
The NIMHD supports two programs that focus on transdisciplinary and 
translational research: the Centers of Excellence (COE) and the 
Transdisciplinary Collaborative Centers for Health Disparities Research 
(TCC). The COEs, which were established as partnerships between 
academic institutions and community organizations, have been in place 
for over a decade and have reached more than 102 sites, across 31 
States, the District of Columbia, Puerto Rico, and the U.S. Virgin 
Islands. The COEs are addressing health disparities research along the 
translational spectrum from basic science to clinical research, with 
information dissemination a required component.
    The TCC Program, established in fiscal year 2012, supports 
research, implementation, and dissemination of activities that 
transcend customary discipline-specific approaches conducted at the 
local level. Transdisciplinary research collaboration at the regional 
level provides opportunities for academic institutions, community-based 
organizations, and other partners to conduct targeted research to 
respond to specific population-based, environmental, sociocultural, and 
political factors that influence health within a particular region.
    The Collaborative Research Center for American Indian Health is 
bringing together tribal communities and health researchers from a 
variety of disciplines to work together to address the significant 
health disparities experienced by American Indians in South Dakota, 
North Dakota and Minnesota, particularly the social determinants of 
health and its application to programming public health interventions. 
The National Transdisciplinary Collaborative Center for African 
American Men's Health is addressing unintentional and violence-related 
injuries as well as chronic diseases that affect African American men 
across the life course, as part of a national initiative.
                          community engagement
    Active community involvement in biomedical and behavioral research 
is essential to improving the health of the public. The NIMHD 
Community-Based Participatory Research (CBPR) Initiative supports the 
development, implementation, and evaluation of intervention research 
that utilizes the principles of community engagement as partners in the 
full spectrum of research. A number of CBPR planning phase and 
dissemination phase projects are under way. The Partnerships to Improve 
Lifestyle Interventions and Partners in Care programs tested the 
effectiveness of a culturally adapted diabetes self-management 
intervention among Native Hawaiians and Pacific Islanders. The study 
found improvements in weight loss, physical capacity, and diabetes 
self-management.
    Another CBPR project focused on a culturally appropriate, church-
based Hepatitis B screening and vaccination intervention program for 
Korean Americans which found increased screening and immunization rates 
in the intervention group compared with the control group. Academic-
community partnerships were essential in balancing science and 
community needs in the design and conduct of the needs assessment, 
pilot and full-scale clinical trial.
                  research training and infrastructure
    In order to advance the science and speed translation of 
discoveries into better health outcomes for all Americans, it is 
critical to expand and diversify the Nation's workforce of well-trained 
scientists who are dedicated to improving minority health and 
eliminating health disparities. A diverse biomedical workforce will 
improve the quality of the educational and training environment, 
balance and broaden the perspective in setting research priorities, 
improve the ability to recruit subjects from diverse backgrounds into 
clinical research protocols, and improve the Nation's capacity to 
address and eliminate health disparities. NIMHD-supported programs to 
train researchers to conduct minority health and health disparities 
research are focusing on providing educational, mentoring, and/or 
career development programs for individuals from health disparity 
populations that are underrepresented in the biomedical, clinical, 
behavioral, and social sciences. NIMHD continues to support research 
training and infrastructure through its Research Endowment Program, 
Building Research Infrastructure and Capacity Program, and Research 
Centers in Minority Institutions Program.
                               conclusion
    NIMHD has a unique and critical role at the NIH as the focal point 
for conducting and coordinating research on minority health and health 
disparities, raising national awareness about the prevalence and impact 
of health disparities, and the dissemination of effective individual, 
community, and population-level interventions to reduce and ultimately 
eliminate health disparities. NIMHD is looking forward to identifying 
new opportunities to accelerate the pace of research and to advance its 
mission through strengthening partnerships and enhancing its role in 
the community.
                                 ______
                                 
        Prepared Statement of Roderic I. Pettigrew, Ph.D., M.D.
    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 2015 NIBIB budget request of $328,532,000 is 
$2,173,000 more than the fiscal year 2014 enacted level of 
$326,359,000.
    NIBIB is dedicated to improving human health through the 
integration of the physical and biological sciences. NIBIB's mission 
spans the entire health spectrum and is not limited to a single 
disease, group of illnesses, or population. Working with doctors from 
every field of medicine and bringing together teams of scientists and 
engineers from many different backgrounds, NIBIB aims to develop 
innovative approaches to healthcare. Our research focus is to improve 
the understanding, detection, treatment and ultimately, the prevention 
of disease.
  innovation in treating spinal cord injury: new hope for those with 
                               paralysis
    Building on a long history of research on restoring function in 
spinal cord injury, researchers have discovered a fundamentally new 
intervention that led to voluntary movement in individuals with 
complete paralysis. This outcome, initially seen in a single 
individual, has now been reported in three successive patients, all of 
whom had been paralyzed for more than 2 years. This achievement is a 
significant milestone in spinal cord injury research. In the approach, 
electrical stimulation is applied to the surface of the spinal cord 
through a surgically implanted device that is normally used for the 
suppression of back pain. After just a week of stimulation, on average, 
the patients were able to voluntarily move their legs and flex their 
feet and toes when the stimulator was turned on. With continued daily 
stimulation and extensive physical training, the patients saw 
improvements in their movements and could initiate them with decreased 
stimulation. With their stimulators turned on, the patients are now 
able to stand for about an hour. Restored function was accompanied by 
increased muscle mass. In addition, these individuals have regained 
bladder and bowel function and experienced improvements in autonomic 
responses such as sweating and return of sexual function in some cases.
      immunoengineering to modifiscal year immune system responses
    The immune system is the body's defense against an array of 
infectious agents. However, the immune system can also trigger many 
diseases such as diabetes, rheumatoid arthritis, lupus or multiple 
sclerosis; this occurs when immune cells are directed against an 
individual's own cells and is referred to as autoimmunity. As our 
understanding of the immune system increases, we are approaching a 
point where the immune response can be engineered to enhance or reduce 
specific responses. Two recent examples highlight this 
``immunoengineering'' approach. In the first case, the problem being 
addressed is improving targeted delivery of chemotherapeutic drugs to 
tumors. Nanoparticles can be used to ferry chemotherapy directly to 
tumors, minimizing exposure of these toxic medications to healthy 
tissues in the body. Researchers have found a way to ferry 
nanoparticles carrying chemotherapy drugs past cells of the immune 
system, which would normally engulf the particles, preventing them from 
reaching their target. The technique takes advantage of the fact that 
all cells in the human body display a protein on their membranes that 
functions as a specific ``passport'' in instructing immune cells not to 
attack them. By attaching a small piece of this protein to 
nanoparticles, scientists were able to get immune cells in mice to 
recognize the particles as ``self'' rather than foreign particles, and 
thereby not attack them. The nanoparticles also have other labels that 
can concentrate the drugs in the tumors, so higher doses of 
chemotherapy are delivered to the tumor.
    In a second example, researchers have developed a strategy to 
modulate the immune system to halt the progress of a disease model of 
multiple sclerosis in mice. In multiple sclerosis, the immune system 
attacks the myelin sheaths that surround nerve cells. To stop this 
attack, engineered nanoparticles are coated with myelin antigens, and 
these nanoparticles are presented to another set of cells in the immune 
system that re-identifies myelin as `self' rather than `foreign'. The 
result is that the immune system stops attacking myelin as a foreign 
body, and the disease progression is halted. This approach begins to 
take advantage of the complex control of immune response which contains 
multiple positive and negative feedback loops in order to selectively 
turn off one specific inflammatory response. It holds promise for 
treating multiple sclerosis and other autoimmune diseases that 
previously have escaped effective therapies.
              cancer detection from a routine blood sample
    Most cancers spread by way of the circulatory system. As a result, 
there are cancer cells present in blood samples. The number of cells, 
however, is so low that they have been difficult or impossible to find. 
The problem is to find and isolate the few cancer cells from the 
billions of other cells that are present in the blood. Researchers over 
the past several years have developed new techniques to find these 
cells, but those techniques have generally been destructive to the 
cancer cells. Now, with a new sorting technology, researchers have 
demonstrated the ability to sort the cancer cells and, of equal 
importance, to collect them for further analysis. After collection, the 
circulating tumor cells can be subjected to the full array of analysis 
techniques available to normal tissue biopsies of a tumor. This 
technology also permits sorting, using a variety of markers that allow, 
for example, the identification of triple negative breast cancer cells. 
Successful isolation has been demonstrated in several other cancers 
including lung, prostate, pancreas, breast, and melanoma. This new tool 
has the potential to improve both the early diagnosis and effective 
treatment of cancer.
an implantable artificial kidney holds promise for patients on dialysis
    Expenditures in the United States for end stage renal disease 
exceed $40 billion annually. Treatment of end stage renal disease 
includes renal transplant and thrice-weekly, in-center hemodialysis. 
Renal transplant is limited to a small fraction of potential recipients 
by a shortage of donor organs. As a result, more than 400,000 Americans 
are on dialysis, which is expensive, inconvenient, and over time 
associated with significant morbidity and mortality. Researchers are 
developing an implantable bioartificial kidney called the Implantable 
Renal Assist Device (iRAD), in which a patient's blood will be filtered 
through an artificial kidney consisting of silicon nanopore membranes 
and a bioreactor of cells to mimic the functions of a healthy kidney. 
Such a device could offer numerous advantages for patients including: 
freedom of mobility, decreased infection risk due to a permanent 
vascular connection, and continuous treatment, which avoids the build-
up of toxins that occurs between in-center hemodialysis visits. In 
addition, incorporation of the patient's own cells could provide normal 
renal metabolic function that would be more physiologic than dialysis 
and not require anti-rejection drugs used for transplant. This combined 
filtration and metabolic treatment has been shown to work using a room-
sized external model. Multi-day animal model testing to demonstrate 
hemofilter biocompatiblity has been conducted. Although human studies 
have not been initiated with the iRAD, these researchers are working 
with the Food and Drug Administration (FDA) on an initiative that 
facilitates new ways for FDA staff and innovators to jointly bring 
breakthrough medical device technologies to patients faster and more 
efficiently.
         smart homes for healthy independent living at all ages
    The population is aging and, increasingly, medical treatment 
involves the management of chronic and/or degenerative diseases. 
Management of such conditions requires monitoring and early 
intervention to prevent more severe complications. The rapid 
development and ever expanding capabilities of smart phones, advanced 
sensors, point-of-care diagnostics, and integrated Internet 
connectivity provides a framework on which new healthcare models can be 
developed to provide this monitoring and intervention. Investigators 
are testing real-time home observation of high-risk patients for early 
signs of illness, using a built-in camera, computer tablet and a smart 
phone for simultaneous monitoring of daily activities by family members 
and health professionals. This includes analysis of daily habits, 
mobility patterns, and gait rate and rhythm as indicators of change in 
health status. Developing automated technologies to help identify early 
indicators of changes in health status will extend the amount of time 
individuals can live independently in their own homes.
                                 ______
                                 
        Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's fiscal year 2015 budget request for the National 
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the 
National Institutes of Health (NIH). The fiscal year 2015 budget 
includes $1,743,336,000, which is $1,462,000 above the comparable 
fiscal year 2014 appropriation of $1,741,874,000. Complementing these 
funds is an additional $150,000,000 authorized in fiscal year 2015 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 research is achieving remarkable progress and 
building the foundation for previously unimaginable strategies to 
improve health and quality of life. For example, recent research has 
better defined human brown adipose (fat) tissue in the neck, and has 
further elucidated the role of a family of proteins as molecular 
signals regulating brown fat physiology--findings that could help 
inform new approaches for altering metabolism to clinical advantage. 
The microorganisms that inhabit the gastrointestinal tract are 
important factors in maintaining or tipping the balance between health 
and disease. A recent study of young twin pairs in Malawi revealed that 
gut microbes may play an important role in causing severe malnutrition 
in children that persists in spite of nutritional interventions. 
Gaining new insight into gastric bypass surgery, scientists studying a 
mouse model found that restructuring of the digestive tract leads to 
weight loss and metabolic benefits in part by altering the communities 
of bacteria that normally live in the intestines. Another study has 
shown that deletion of the protein olfactomedin-4 in white blood cells 
improves their ability to eradicate infections with the harmful 
bacteria Staphylococcus aureus in an animal model of the immune 
disorder chronic granulomatous disease. Scientists supported by our 
Institute have used a series of genetically engineered mice to identify 
the contribution of different kidney cell subtypes to the process of 
fibrosis that follows kidney injury, confirming myofibroblasts' 
contribution to fibrosis and tracking their developmental origins--
results that could inform future treatment strategies. Scientists have 
discovered a link between two proteins known to contribute to the most 
common form of polycystic kidney disease and a cell-surface structure 
in a subset of kidney cells in mice. NIDDK-supported researchers 
conducted a study in mice showing that chemotherapy damages nerves that 
regulate bone marrow niches responsible for making new blood cells; 
future research in humans could explore ways to reduce nerve damage and 
improve blood cell regeneration after chemotherapy. A new study has 
shown that it may one day be possible to treat people with cystic 
fibrosis (CF) using a combination of medicines that work cooperatively 
to stabilize an aberrant form of CFTR, the protein that is defective in 
CF.
    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 generating or repairing nephrons that can function 
within the kidney; diet-host microbiome interactions in autoimmune and 
metabolic diseases; and a collaborative research network on disease 
modeling and tissue repair and regeneration.
                clinical science and precision medicine
    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, researchers studying type 1 diabetes have used smartphone 
technology to move a step closer toward developing an artificial, 
bionic, pancreas. Scientists reported data on insulin resistance and 
secretion that suggest early and rapid deterioration of pancreatic beta 
cell function in youth with type 2 diabetes, underscoring the need to 
intervene early and aggressively. Researchers have found that patients 
with irritable bowel syndrome show an improvement in symptoms following 
a short course of group therapy involving psychological and educational 
approaches. Recent research has shown that in dialysis patients with 
diabetes, measuring another set of modified blood proteins may better 
predict the risk of death and cardiovascular disease than the current 
standard test to assess blood glucose control.
    The NIDDK supports research aimed at tailoring treatments for 
disease to the individual characteristics of each patient. For example, 
a detailed genetic study has now identified rare mutations of the 
SLC30A8 gene that sharply reduce risk for type 2 diabetes in several 
different racial/ethnic populations, suggesting that inhibitors of the 
Slc30A8 protein may one day be therapeutically valuable. New research 
has greatly expanded knowledge of the specific genetic mutations 
capable of causing CF, leading to much more comprehensive CF genetic 
testing. A recently discovered set of mutations in the DGKE gene may be 
behind some cases of the serious blood disorder hemolytic uremic 
syndrome. Scientists participating in NIDDK's Childhood Liver Disease 
Research and Education Network have utilized patient samples and an 
animal model to identify a genetic deletion in the GPC1 gene that may 
play a role in the development of biliary atresia. NIDDK researchers 
have created and confirmed the accuracy of a mathematical model that 
predicts how weight and body fat in children respond to adjustment in 
diet and physical activity.
                    nurturing talent and innovation
    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. One major objective of the Network of Minority 
Health Research Investigators is to encourage and facilitate 
participation of members of underrepresented population groups and 
others interested in minority health in the conduct of biomedical 
research. In addition, several NIDDK-sponsored programs provide 
opportunities for minority students to obtain research experience. The 
NIDDK's Short-Term Education Program for Underrepresented Persons, or 
STEP-UP, provides research education grants to seven institutions to 
coordinate high school and undergraduate STEP-UP programs that enable 
students to gain summer research experience and training.
          integrating science-based information into practice
    NIDDK also will continue to support education, outreach, and 
awareness programs. Research clearly shows that communications alone 
about the seriousness of diabetes will not reverse the diabetes 
epidemic. The NIDDK is committed to focusing more efforts to promote 
the theme of moving from awareness to action, by providing behavior 
change tools and other resources to help people with diabetes and those 
at risk make and sustain lifestyle changes. For example, the NIDDK-CDC 
National Diabetes Education Program has developed the Diabetes 
HealthSense Web site, an online library of tools and resources 
developed by partners from around the country to address a wide array 
of psychosocial and lifestyle challenges. The NIDDK's National Kidney 
Disease Education Program (NKDEP) works to identify people with chronic 
kidney disease (CKD) and promote the implementation of evidence-based 
interventions, focusing on populations at highest risk for CKD and the 
providers who serve them. In addition, through collaborative community 
partnerships with organizations such as the Chi Eta Phi Nursing 
Sorority and the American Diabetes Association, NKDEP brings NIH 
science-based information to the grassroots.
    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 Paul A. Sieving, M.D., Ph.D.
    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 2015 budget 
proposal is $675,168,000, which is $0.9 million more than the fiscal 
year 2014 enacted level of $674,249,000. 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.
                     nei audacious goal initiative
    Vision research is often on the cutting edge of biomedical 
research, from the first successful gene therapy clinical trials that 
restored some visual function in patients with an inherited form of 
blindness, to clinical trials for macular degeneration using tissue 
derived from embryonic stem cells, to a retinal electrical prosthesis, 
approved this past year by the FDA, after years of development by 
Second Site, a small business that received research support from both 
NEI and the Department of Energy. NEI is now starting a new chapter in 
its ambitious research agenda. I have launched a new initiative--The 
NEI Audacious Goal Initiative in Vision Research and Blindness 
Rehabilitation--to identify a groundbreaking long-term research goal 
that will markedly improve prevention and treatment of common eye 
diseases.
    We started this effort over a year ago by soliciting audacious 
ideas from scientists, stakeholders, patients, clinicians, and the 
public through a Challenge Competition. After a thorough scientific 
review of more than 500 submissions, we chose 10 winning entries, which 
were presented and intensively discussed at the NEI Audacious Goals 
Development Meeting last year. In May, I announced that the NEI 
Audacious Goal will be to Regenerate Neurons and Neural Connections in 
the Eye and Visual System. To kick start this initiative, we will soon 
release funding opportunities focusing on different components of this 
goal. Implementation of work toward the goal will include oversight, 
guidance, and direction from non-governmental consultant experts.
    This goal will focus on two types of retinal neuronal cells that 
underpin many of the leading causes of visual impairment. One such 
target is photoreceptor cells, the specialized neurons in the retina 
that detect light and initiate the neural response. Blindness in some 
diseases, such as retinitis pigmentosa, is a direct result of 
photoreceptor cell death, whereas in other diseases such as diabetic 
retinopathy or macular degeneration, damage elsewhere in the retina 
indirectly causes photoreceptor cells to die.
    Retinal ganglion cells (RGCs) are the second cell type targeted in 
this program. These neurons reside in the retina but send long 
projections (axons in the optic nerve) that connect to the brain. When 
RGCs degenerate and die in diseases such as glaucoma and multiple 
sclerosis, vision signals from the eye can't get to the brain. Two of 
the primary scientific challenges of this initiative include protecting 
newly regenerated cells from dying, and inducing them to form 
appropriate neural connections in the brain. Success in achieving this 
goal will not just revolutionize how we approach diseases in vision, 
but all of neuroscience.
    NEI is also a key contributor and participant in the President's 
BRAIN initiative, which seeks to decode the brain, just as the Human 
Genome Initiative decoded DNA. While NEI's Audacious Goal is 
independent from the BRAIN initiative, the eye is the gateway to the 
brain--it is the most accessible part of the central nervous system. 
There is good opportunity for synergy between these exciting 
initiatives.
                         new areas of emphasis
    In the process of identifying our Audacious Goal, we also 
identified two high-priority, complementary areas of emphasis, for 
which we have released two funding opportunities and are currently 
reviewing grant applications: Molecular Therapy for Eye Disease; and 
the Intersection of Aging and Biological Mechanisms of Eye Disease. 
With recent advances in genomics, we now have a good understanding of 
genes and molecules that are altered in many diseases. The National 
Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE), is a 
critical resource created by NEI for identifying the mutated genes in 
patients with inherited eye disorders and giving researchers access to 
DNA samples (over 4,000 collected since 2006), clinical information, 
and patients looking to participate in research studies. But the 
current tools at our disposal to treat genetic diseases are limited. 
Building on our recent successes in gene therapy, the exciting 
potential of designing personalized therapies to correct mutant genes 
lies in the research ahead of us over the next decade.
    Many eye diseases are associated with aging: from cataracts and 
presbyopia, which are common in all adults as they age, to some of the 
leading vision impairment diseases, age-related macular degeneration 
(AMD) and glaucoma. Understanding what aspects of the aging process 
contribute to eye disease has the potential to delay the onset of 
vision loss or even avert the disease.
                   nei regenerative medicine program
    Also contributing to the Audacious Goal Initiative are researchers 
at NEI, working with the NIH Center for Regenerative Medicine to create 
retinal tissues from induced pluripotent stem (iPS) cells for several 
basic and translational research applications. iPS cells can be 
generated from any adult cell, and then converted into virtually any 
other type of cells. A major thrust of this program is to derive iPS 
cells from patients with retinal diseases. Then, the iPS cells are 
differentiated to form retinal pigment epithelial (RPE) cells or 
photoreceptors and studied to identify disease-causing molecular 
pathways. Diseases of interest currently include AMD, Best disease, 
late-onset retinal degeneration, Stargardt's disease, and retinitis 
pigmentosa. This program is exploiting these techniques to develop 
high-throughput drug screens to identify potential therapeutic 
compounds for treating retinal degenerative diseases.
    Another potentially powerful application of iPS cell technology is 
to generate iPS cells from normal tissue and then differentiate those 
cells into monolayer sheets of RPE for tissue transplants. NEI 
intramural investigators are engineering a bio-degradable scaffold in 
order to grow the RPE tissue and transfer it to patients with RPE-
associated retinal degenerative diseases. In fiscal year 2015, the stem 
cell program will also use stem cell technologies to evaluate synaptic 
connections in 3-D retinas derived from iPS cells.
    As I reflect on the remarkable progress the vision community has 
made in these past few years, I can hardly anticipate the exciting 
opportunities that lay ahead.
                                 ______
                                 
          Prepared Statement of Martha Somerman D.D.S., Ph.D.
    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 2015 NIDCR budget of $397,131,000 includes an 
increase of $29,000 over the enacted fiscal year 2014 level of 
$397,102,000.
    In keeping with its mission to improve the Nation's oral health, 
the breadth of NIDCR's research touches the lives of nearly all 
Americans. Our research spans multiple disciplines, scientific 
approaches, and research directions, all focused on the goal of 
improving people's lives. Today, I will highlight selected areas of 
particular promise in our efforts to understand the development of 
tissues of the face and head, conquer oral infectious diseases through 
better understanding of the body's own defenses, help people facing 
chronic orofacial pain conditions, and develop new approaches to 
improve oral cancer survival.
                      development and regeneration
    The human face is among the body's most distinctive structures. 
NIDCR is the leading supporter of research on the development of the 
human face and skull, collectively known as the craniofacial region. By 
defining the complex web of environmental and genetic instructions that 
drive craniofacial development, the hope is that scientists one day 
will learn to repair damaged or malformed facial structures such as 
cleft lip and palate by harnessing the body's ability to heal itself.
    Five years ago, NIDCR began assembling information on the genetic 
code that instructs facial development with the launch of its FaceBase 
Consortium. Through this endeavor, scientists have assembled nearly 500 
publicly available datasets involving the biological instructions for 
the middle region of the human face, which includes the nose, upper 
lip, and palate, or roof of the mouth. FaceBase begins a second phase 
this year, as it expands its focus to include studies on additional 
regions of the face. This new phase will add to our knowledge about the 
genetics that underlie craniosynostosis, a birth skull defect that may 
result in severe and permanent problems if not corrected.
    NIDCR is also translating knowledge about craniofacial development 
into tools to re-grow bone and cartilage damaged by disease or injury. 
Ongoing studies are using the power of stem cells to regenerate 
tissues, improve wound healing, and help control inflammatory-
associated diseases of the mouth. Related research uses specially 
designed stable small molecules modified from naturally occurring 
molecules called resolvins that control inflammation in a wide range of 
conditions to target oral inflammatory diseases such as periodontitis. 
We envision a future where natural tool kits are used to regenerate and 
repair damaged teeth, diseased gums, and broken or defective bones by 
utilizing stem cells and adapting natural molecules and processes.
              oral infections, immunity and the microbiome
    The NIH's human microbiome project has reinforced that no man is an 
island. Although human beings coexist with a plethora of 
microorganisms, microbial cells outnumber human cells by 10 to 1, 
living on surfaces of our body in sticky layers of polymicrobial 
communities called biofilms. Under normal circumstances, these 
microbial guests coexist with us and even contribute to sustaining 
human health. But, if conditions in some part of the body are altered, 
the balance is disrupted, and the disease-causing organisms that live 
on our gums and teeth can overwhelm our natural immune defense systems 
causing oral infectious diseases such as tooth decay and periodontal 
diseases. NIDCR-supported scientists are beginning to assemble the 
precise molecular details of how select oral pathogens destabilize the 
immune system to cause oral diseases. For example, individuals with 
leukocyte adhesion deficiency (a rare genetic disorder affecting the 
body's immune system) suffer from frequent bacterial infections, 
including severe periodontitis. New research has demonstrated that 
blocking certain molecules that are part of the individual's own immune 
system can reverse this inflammation and resulting bone loss.
    In combination with these discoveries, we have made great strides 
in understanding how an individual's own microbiome affects his or her 
health and disease. NIDCR continues to invest in microbiome research, 
supporting a database of information on oral microbes that will one day 
allow dentists to visualize the microbes within a patient's oral 
biofilm in real time--offering new tools to diagnose and treat oral 
disease. For example, a dentist might observe an overgrowth of a 
particular type of bacteria that uniquely predisposes a patient to 
tooth decay, and could treat that bacterial imbalance to prevent the 
individual from developing cavities. These emerging leads will not only 
guide future personalized dental treatment for millions of Americans; 
they will help scientists throughout biomedical research to inform 
better treatment approaches for other microbe-host diseases such as 
colitis.
                   temporomandibular joint disorders
    Thousands of Americans this year will be diagnosed with a painful 
and debilitating disorder of the jaw called temporomandibular joint and 
muscle disorder (TMD). Some of these individuals will recover after a 
single bout of TMD, while others will go on to develop chronic 
disease--and their healthcare providers, currently, are unable to 
predict the likely outcome for any individual patient. NIDCR-supported 
research is providing key insights that could identify people at risk 
for developing TMD, and predict the likelihood of progression to 
chronic disease. In 2006, NIDCR launched the Orofacial Pain: 
Prospective Evaluation and Risk Assessment (OPPERA) study. The study's 
latest findings present the most in-depth picture to date of the 
factors that may contribute to a person's developing an initial bout of 
painful TMD. Among the many interesting findings is that there is 
almost no difference in the rate at which men and women develop TMD for 
the first time. And yet, females are far more likely to progress to 
chronic TMD than males. Researchers will continue to examine potential 
causes of this difference, such as hormonal regulatory factors, leading 
to more targeted strategies for detecting and managing TMD in the 
future.
    Although TMD specifically afflicts the jaw, OPPERA researchers 
found only about 15 percent of OPPERA participants diagnosed with 
chronic TMD have orofacial pain only. The other 85 percent have 
additional ailments, many of which are painful in nature, including 
chronic fatigue syndrome, fibromyalgia headache, and low back pain. 
This finding demonstrates that first-onset and chronic TMD are complex 
disorders that must be understood within a biological, psychological, 
and social model of illness. NIDCR will continue to help lead the way 
for all those battling these chronic conditions to find relief through 
a more accurate diagnosis and more personalized care.
               oral cancer and human papillomavirus (hpv)
    When many people hear the acronym HPV, they think of its 
association with cervical cancer. But over the last decade, various 
types of this virus also have been shown to contribute to head and neck 
cancers. In fact, the incidence of HPV-related head and neck cancer has 
risen steadily over the last decade and if the pace continues, it will 
soon surpass the incidence of cervical cancer. This trend is 
particularly alarming because no effective diagnostic test currently 
exists to detect early HPV-related head and neck cancer. Tools are 
needed to screen those at increased risk of the condition and to test 
for possible persistence of the condition following therapy.
    NIDCR will help to fill this public health need by launching an 
initiative to develop a viable diagnostic test. The initiative will 
identify DNA markers associated with HPV-related head and neck cancer, 
develop and validate saliva and plasma-based diagnostic tests, and 
evaluate and test the biomarkers in humans. Clinical studies are also 
ongoing to establish the safety and feasibility of administration of a 
DNA vaccine in certain HPV-associated head and neck cancer patients. 
NIDCR scientists recognize the urgency of developing innovative 
approaches to detect oral cancer early, when personalized treatment can 
be more successful, leading to better patient outcomes.
    There has never been a better time to take advantage of the 
remarkable opportunities in science and technology waiting at our 
doorstep. Seizing this moment brings us closer to preventing and 
treating dental, oral, and craniofacial conditions as well as other 
diseases that share risk factors and therapeutic strategies.
                                 ______
                                 
         Prepared Statement of Lawrence A. Tabak, D.D.S., Ph.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for the Office of the Director (OD) of 
the National Institutes of Health (NIH). The fiscal year 2015 OD budget 
of $1,451,786,000 includes an increase of $51,033,000 above the 
comparable fiscal year 2014 level of $1,399,753,000.
    The OD promotes and fosters NIH research and research training 
efforts in the prevention and treatment of disease through the policy 
oversight of both the extramural grant and contract award functions and 
the Intramural Research program. The OD stimulates specific areas of 
research to complement the ongoing efforts of the Institutes and 
Centers through the activities of several cross-cutting program 
offices. The OD also develops policies in response to emerging 
scientific opportunities employing ethical and legal considerations; 
provides oversight and management of peer review policies; coordinates 
information technology across the Agency; and, coordinates the 
communication of health information to the public and scientific 
communities. Moreover, the OD provides the core management and 
administrative services, such as budget and financial management, 
personnel, property, and procurement services, ethics oversight, and 
the administration of equal employment policies and practices.
    The fiscal year 2015 request will also support activities managed 
by the OD's operational offices. OD Operations is comprised of several 
OD Offices that provide advice to the NIH Director, policy direction 
and oversight to the NIH research community and administer centralized 
support services essential to the NIH mission.
    The functions and initiatives of the OD's research offices are 
described in detail as follows:
 division of program coordination, planning, and strategic initiatives 
                                (dpcpsi)
    DPCPSI provides leadership for identifying, reporting, and funding 
trans-NIH research that represents important areas of emerging 
scientific opportunities, rising public health challenges, or knowledge 
gaps that merit further research and would benefit from collaboration 
between two or more Institutes or Centers (ICs), or from strategic 
coordination and planning.
    The Division includes major programmatic offices that coordinate 
and support research and activities related to HIV/AIDS, women's 
health, behavioral and social sciences, disease prevention, dietary 
supplements, research infrastructure, and science education. DPCPSI 
serves as a resource for the ICs and the NIH Office of the Director for 
portfolio analysis by developing, using, and disseminating data-driven 
approaches and computational tools.
    The fiscal year 2015 budget for DPCPSI, including the immediate 
Office of the DPCPSI Director, the Offices of Portfolio Analysis and 
Program Evaluation and Performance, and the Office of Strategic 
Coordination is $11,138,000.
           office of research infrastructure programs (orip)
    ORIP provides support for a variety of research infrastructure 
needs, including animal models and facilities; research models, human 
biospecimens, and biological materials; training and career development 
for veterinarians engaged in research; the acquisition of state-of-the-
art and shared and high-end instrumentation; and research resources 
grants to expand, re-model, renovate, or alter existing research 
facilities. The ORIP budget for fiscal year 2015 is $275,654,000.
              science education partnership awards (sepa)
    The goal of the Science Education Partnership Awards (SEPA) program 
is to invest in educational activities that enhance the training of a 
workforce to meet the Nation's biomedical, behavioral and clinical 
research needs. The SEPA program encourages the development of 
innovative educational activities for pre-kindergarten to grade 12 (P-
12), teachers and students from underserved communities with a focus on 
Courses for Skills Development, Research Experiences, Mentoring 
Activities, Curriculum or Methods Development or Informal Science 
Education (ISE) exhibits, and Outreach activities. In fiscal year 2015, 
the SEPA Program will be coordinated with the Department of Education 
to ensure that program activities are aligned with ongoing P-12 reform 
efforts included in the President's budget request. In fiscal year 
2015, the budget for SEPAs is $18,541,000.
                   the office of aids research (oar)
    OAR plays a unique role at NIH by serving as a model of trans-NIH 
planning and management, vested with primary responsibility for 
overseeing all NIH AIDS-related research. OAR coordinates the 
scientific, budgetary, legislative, and policy elements of the NIH AIDS 
research program. OAR's response to the AIDS epidemic requires a unique 
and complex multi-institute, multi-disciplinary, global research 
program. This diverse research portfolio demands an unprecedented level 
of scientific coordination and management of research funds to identify 
the highest priority areas of scientific opportunity, enhance 
collaboration, minimize duplication, and ensure that precious research 
dollars are invested effectively and efficiently, allowing NIH to 
pursue a united research front against the global AIDS epidemic. The 
fiscal year 2015 budget for OAR is $61,923,000.
     the office of behavioral and social sciences research (obssr)
    OBSSR furthers the mission of the NIH by emphasizing the critical 
role that behavioral and social factors play in health, healthcare and 
well-being. OBSSR serves as a liaison between NIH and the extramural 
research communities, other Federal agencies, academic and scientific 
societies, national voluntary health agencies, the media, and the 
general public on matters pertaining to behavioral and social sciences 
research. OBSSR's vision is to bring together the biomedical, 
behavioral, and social science communities to work more collaboratively 
to solve the pressing health challenges facing our Nation. OBSSR also 
coordinates and helps support the NIH Basic Behavioral and Social 
Science Opportunity Network, a trans-NIH initiative to expand the 
agency's funding of basic behavioral and social sciences research. The 
fiscal year 2015 budget for OBSSR is $26,094,000.
            the office of research on women's health (orwh)
    Since its creation in 1990, ORWH has worked to ensure the inclusion 
of women in NIH clinical research, to advance and expand women's health 
research, and to promote advancement of women in biomedical careers. 
ORWH is the focal point for NIH women's health research and works in 
partnership with the NIH ICs to incorporate a women's health and sex 
differences research perspective into the NIH scientific framework. 
ORWH activities are guided by the 2010 NIH Strategic Plan for Women's 
Health Research. This strategic plan outlines six goals to maximize 
impact of NIH research effort. The NIH strategic plan for women's 
health and sex differences research serves as a framework for 
interdisciplinary scientific approaches. The fiscal year 2015 budget 
for ORWH is $40,903,000.
                 the office of disease prevention (odp)
    The ODP is responsible for assessing, facilitating, and stimulating 
research in disease prevention and health promotion, and disseminating 
the results of this research to improve public health. Research on 
disease prevention is an important part of the NIH mission because the 
knowledge gained from this research leads to stronger clinical 
practice, health policy, and community health programs. In early fiscal 
year 2014, ODP released its first strategic plan. This plan outlines 
the priorities that the Office will focus on over the next 5 years and 
highlights the ODP's role in advancing prevention research at the NIH. 
The fiscal year 2013 budget for ODP is $5,861,000. The Office of 
Dietary Supplements (ODS) is within the ODP organizational structure. 
The mission of the ODS is to strengthen knowledge and understanding of 
dietary supplements by evaluating scientific information, stimulating 
and supporting research, disseminating research results, and educating 
the public to foster an enhanced quality of life and health for the 
U.S. population. The fiscal year 2015 budget for ODS is $26,786,000.
     the office of strategic coordination (osc) and the common fund
    OSC oversees the management of the Common Fund (CF), working with 
trans-NIH teams for each of the more than 30 Common Fund programs. 
These teams ensure that each program meets the criteria of Common Fund 
programs to synergize with IC funded research. The NIH CF was created 
by the 2006 NIH Reform Act which codified the approach of the NIH 
Roadmap for Medical Research to support cross-cutting, trans-NIH 
programs that require participation by at least two NIH ICs or would 
otherwise benefit from strategic planning and coordination. CF programs 
tackle major challenges in biomedical research that affect many 
diseases or conditions or that broadly relate to human health. The CF 
provides limited-term funding for goal-driven, coordinated research 
networks to generate data, solve technological problems, and/or pilot 
resources and tools that will stimulate the broader research community. 
The fiscal year 2015 budget for the Common Fund is $583,039,000.
                loan repayment and scholarship programs
    The mission of the NIH Intramural Loan Repayment Programs is to 
seek to recruit and retain highly qualified physicians, dentists, and 
other health professionals with doctoral-level degrees. These programs 
offer financial incentives and other benefits to attract highly 
qualified physicians, nurses, and scientists into careers in 
biomedical, behavioral, and clinical research as employees of the NIH. 
The Undergraduate Scholarship Programs (UGSP) offers competitive 
scholarships to exceptional college students from disadvantaged 
backgrounds that are committed to biomedical, behavioral, and social 
science health-related research careers at the NIH. The fiscal year 
2015 budget for ILRSP is $7,145,000.
    I am happy to answer any questions you may have about the OD's 
programs and activities as well as our plans for the upcoming year.
                                 ______
                                 
               Prepared Statement of Nora D. Volkow, M.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2015 President's budget request for the National 
Institute on Drug Abuse (NIDA). The fiscal year 2015 budget request for 
NIDA is $1,023,268,000, which reflects an increase of $7,514,000 over 
the fiscal year 2014 level of $1,015,754,000.
    The impact of substance abuse in this country is daunting; the 
economic toll alone exceeds $700 billion \1\ a year in healthcare, 
crime-related, and productivity losses. NIDA strives to translate the 
returns of its investments in genetics, neuroscience, pharmacotherapy, 
and behavioral and health services research into new strategies for 
preventing and treating substance abuse and addiction. This scientific 
investment is crucial if we are to tackle rapidly evolving public 
health threats such as the increase in marijuana use among young people 
and the growing prevalence of opioid addiction and overdose deaths.
---------------------------------------------------------------------------
    \1\ U.S.DHHS. The Health Consequences of Smoking--50 Years of 
Progress: A Report of the Surgeon General. Atlanta, GA, CDCP, National 
Center for Chronic Disease Prevention and Health Promotion, Office on 
Smoking and Health, 2014; Rehm J, Mathers C, Popova S, 
Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of 
disease and injury and economic cost attributable to alcohol use and 
alcohol-use disorders. Lancet. 2009 Jun 27;373(9682):2223-33; National 
Drug Intelligence Center (2010). National Threat Assessment: The 
Economic Impact of Illicit Drug Use on American Society. Washington, 
DC: United States Department of Justice.
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           today's basic science for tomorrow's breakthroughs
    There is a fundamental need to understand the complex steps of how 
body chemistry influences behavior and how their disruption can lead to 
addiction. A more detailed and personalized account of these steps will 
lead to a more effective and precise medicine to prevent and treat this 
complex brain disorder.
    In this context, and thanks to recent technological developments, 
we've made important advances in linking genes with behavior. As a 
result, we now have an unprecedented capacity to screen for thousands 
of genetic variations and catalogue how they modulate abuse/addiction 
risk by influencing brain maturation, its neural architecture, and 
behavioral patterns. NIDA researchers are also pursuing genome and 
whole individual sequence analysis to identify genes that modulate 
addiction risk (e.g., genes that regulate drug metabolism), advancing 
their understanding of how environmental factors (e.g., parental style, 
drug exposure) can affect the expression of those genes to either 
strengthen or weaken behavioral patterns through epigenetic changes. 
The systematic identification of genetic, environmental, and 
neurocircuitry variations that modulate abuse/addiction risk will 
revolutionize our prevention and treatment capacities.
                     big opportunities in big data
    Big data sets are essential platforms for the analysis of complex 
systems in genetics and epigenetics, proteomics, brain imaging and 
clinical science. Vast amounts of data are being produced by the 
overlaying of structural and functional brain imaging information that 
links the molecular and cellular data with the expression of higher 
level brain function. A prime example is the new fMRI-based approach to 
generating images of the functional connectivity (FC) among brain 
regions in the absence of any specific task, so called resting state 
(rs) FC. This technique offers a powerful window into circuit-level 
functions that may generate behavioral responses underlying 
vulnerability or a diseased state. Open access to such massive 
databases could lead to the identification of biomarkers of psychiatric 
illness risk including addiction, their trajectories, and treatment 
responses that could be translated for clinical use and the optimal 
management of patients.
    Similarly, NIDA is funding the development of an open source, open 
framework, free National Pain Registry that collects patient 
demographic and treatment information from around the Nation. This 
information can be used to identify which pain management interventions 
are most effective for specific chronic pain patients and predict which 
patients might be at higher risk for opioid addiction. Combined with 
concerted efforts in the pharmacogenomics of prescription opioids, pain 
registries are poised to help us maximize the effectiveness of pain 
treatments while minimizing the likelihood of prescription opioid abuse 
and addiction.
                    nurturing talent and innovation
    NIDA currently supports a great deal of innovative research on drug 
addiction and related health problems such as pain and HIV/AIDS and 
will continue to be at the forefront of training the next generation of 
innovative researchers. The 6-year old Avant-Garde award is a good 
example of a program that stimulates high--impact research that could 
lead to groundbreaking opportunities for the prevention and treatment 
of HIV/AIDS in substance users. NIDA is now crafting a new kind of 
award, which blends NIH's Pioneer and New Innovator award mechanisms. 
This new opportunity, called the ``AVENIR'' award, is designed to 
attract creative young investigators to genetic research on substance 
use disorders and HIV/drug abuse research. Another example is NIDA's 
Cutting-Edge Basic Research Awards (CEBRA), designed to foster highly 
innovative or conceptually creative research that advances our 
understanding of drug abuse and addiction. The latest results of this 
effort include three independent studies exploring the potential 
benefits of neurofeedback training, transcranial magnetic stimulation, 
and meditation on facilitating smoking cessation.
       better pain management: a major goal of addiction research
    Pain management is an important component of high-quality, 
compassionate medical care. Opioid analgesics are among the most 
effective medications for the management of severe pain and frequently 
used for pain treatment. Unfortunately, the benefits of long term 
opioid analgesic treatment are accompanied by significant risk of 
developing drug tolerance (and the need for escalating doses) and 
hyperalgesia (increased pain sensitivity). Exposure to potentially 
rewarding substances, like opioid analgesics, may reinforce drug taking 
behavior for persons with risk factors for addiction and trigger 
relapse in those that are in recovery. These are intrinsic liabilities 
of opioid analgesics that clearly increase the risk for diversion, 
abuse, addiction and overdose.
    NIDA recognizes it has a critical role in ensuring the availability 
of safe and efficacious chronic pain management options while 
minimizing risk of abuse. This is why we are committed to supporting 
research to better predict who is at risk of addiction and to develop 
new classes of effective, non-addicting pain medications. Parallel to 
these efforts, NIDA is proactively pursuing methods to minimize the 
risk of overdose with existing medications. For example, NIDA and 
Lightlake Therapeutics Inc. have partnered to develop an intranasal 
delivery system of naloxone (an opioid receptor blocker that can 
rapidly reverse the overdose of prescription and illicit opioids), 
which could greatly expand its availability and use in preventing 
opioid-related deaths, a public health problem of epidemic proportion 
in the U.S.
                  health consequences of marijuana use
    There is a dangerous and growing misperception that marijuana use 
is harmless, resulting in its status as the most commonly used illicit 
drug in the United States with about 12 percent of people aged 12 and 
over reporting use in the past year.\2\ Marijuana use has been 
associated with significant adverse effects, including addiction, 
cognitive impairment and car accidents. The key to minimizing negative 
outcomes lies with the intensification of our efforts to educate the 
public about the dangers of marijuana use and, with the deployment of 
multipronged, evidence-based strategies to prevent and treat the abuse 
of and addiction to marijuana and other drugs. To meet this challenge, 
NIDA has released several funding announcements to encourage research 
on the impact of changing marijuana policies; and, in partnership with 
other NIH institutes, is planning a large-scale, prospective study that 
follows children prior to drug use into early adulthood to determine 
whether and how marijuana and other commonly used substances (e.g., 
alcohol, tobacco) affect the developing brain.
---------------------------------------------------------------------------
    \2\ Substance Abuse and Mental Health Services Administration, 
Results from the 2012 National Survey on Drug Use and Health: Summary 
of National Findings, NSDUH Series H-46, HHS Publication No. (SMA) 13-
4795. Rockville, MD: Substance Abuse and Mental Health Services 
Administration, 2013.
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                        medications development
    Our current approaches to develop next-generation pharmaceuticals 
take advantage of new technologies using immunotherapeutic or biologic 
(e.g., bioengineered enzymes) approaches for treating addiction. The 
goal is to develop safe and effective vaccines or antibodies that 
target specific drugs, like nicotine, cocaine, and heroin, or drug 
combinations. If successful, immunotherapies--alone or in combination 
with other medications, behavioral treatments, or enzymatic 
approaches--stand to revolutionize how we treat, and maybe even someday 
prevent addiction.
                               conclusion
    The field of addiction research continues to benefit from the 
explosion in genetic knowledge, the advent of precise technologies to 
probe neuronal circuits, and the emergence of openly accessible big 
data platforms. NIDA's research is strategically poised to take full 
advantage of these and other emerging opportunities to develop the 
knowledge base that can be used to reduce drug use in this country.
                                 ______
                                 
             Prepared Statement of Jack Whitescarver, Ph.D.
    Mr. Chairman and Members of the Committee: I am pleased to present 
the President's budget request for fiscal year 2015 for the trans-NIH 
AIDS research program, which is $3,004,973,000. This amount is 
$19,882,000 above the fiscal year 2014 enacted level of $2,985,091,000.
    The authorizing law requires that the Office of AIDS Research (OAR) 
function as ``an institute without walls'' and allocate all dollars 
associated with this area of research across the NIH. Therefore, the 
total for AIDS research includes both extramural and intramural 
research (including research management support, management fund, and 
service and supply fund), buildings and facilities, training, and 
evaluation, as well as research on the many HIV-associated co-
infections and co-morbidities, including TB, hepatitis C, and HIV-
associated cancers. It also includes all of the basic science 
underlying this research. Other disease areas are not reported this 
way. Therefore the total for AIDS-related research is not comparable to 
spending reported for other individual diseases.
                   nih aids research accomplishments
    In the three decades since AIDS was first reported, NIH continues 
to be the global leader in research on HIV and its many related 
conditions. New avenues for discovery have been identified, providing 
possibilities for the development of new strategies to prevent, treat, 
and potentially cure HIV. Recent accomplishments include:
  --Development of new treatments for many HIV-associated co-
        infections, co-morbidities, malignancies, and clinical 
        manifestations;
  --Development of new strategies for the prevention of mother-to-child 
        transmission;
  --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 that the use of antiretroviral therapy by infected 
        individuals can dramatically reduce HIV transmission to an 
        uninfected partner; and that the use of antiretroviral drugs by 
        uninfected individuals can 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; 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.
    In just the past several months, NIH intramural and extramural 
researchers have produced a number of exciting new advances. NIH 
researchers published the results of studies utilizing potent human 
neutralizing antibodies that successfully suppressed a form of HIV in 
primates. This important research could potentially result in a new 
form of treatment for HIV that could be used as an adjunct to 
antiretroviral therapy and could lead to opportunities for novel 
research to treat and potentially cure HIV. NIH-sponsored researchers 
also have made tremendous strides in producing and analyzing proteins 
that may provide an important new pathway in AIDS vaccine design.
    A team of NIH-funded investigators recently reported the first case 
of a newborn in Mississippi who was ``functionally cured'' of HIV 
infection. The infant received antiretroviral therapy immediately after 
being diagnosed at birth but was then lost to follow-up and treatment. 
The now nearly three year-old child has re-entered care with no 
indication of HIV disease and no detectable virus in the absence of 
therapy. Additional studies are under way to better understand this 
case and may lead to clinical trials to see whether a similar approach 
could be used to achieve a ``functional cure'' for other HIV-infected 
newborns. NIH is leading global research efforts to capitalize on all 
of these advances, move science forward, and begin to turn the tide 
against this pandemic.
                           the aids pandemic
    Despite this progress, the HIV/AIDS pandemic will remain the most 
serious global public health crisis of our time until better, more 
effective, and affordable prevention and treatment regimens--and 
eventually a cure--are developed and available around the world. UNAIDS 
reports that in 2012, more than 35 million people were estimated to be 
living with HIV/AIDS; 2.3 million were newly infected (half of them 
women); and 1.6 million people died of AIDS-related illnesses.
    In the United States, 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 Centers for Disease Control and Prevention estimates that 
approximately 1.1 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.
              coordinated trans-nih aids research program
    The NIH AIDS research program is coordinated and managed by the 
OAR, and carried out by nearly every NIH Institute and Center (IC). 
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. Scientific priorities for AIDS research are constantly 
reassessed and reflected in the budget. The annual trans-NIH AIDS 
strategic plan, developed by OAR in collaboration with both government 
and non-government experts, guides the development of the trans-NIH 
AIDS research budget. Each year, the state of the science is reviewed, 
newly emerged and critical public health needs are assessed, and 
scientific opportunities are identified. This annual process culminates 
with the identification of the highest strategic priorities and 
critical research needs. 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 and 
ensures cross-Institute collaboration. The fiscal year 2015 budget 
request reflects the priorities of the fiscal year 2015 strategic 
planning process.
               aids research priorities 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 United States and around the world. The fiscal 
year 2015 budget priorities are:
  --Basic research that will underpin further development of critically 
        needed prevention methodologies, including vaccines;
  --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;
  --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; and
  --Studies to address the increased incidence of co-morbidities, 
        including AIDS-associated malignancies; cardiovascular, 
        neurological and metabolic complications; and premature aging 
        associated with long-term HIV disease and antiretroviral 
        treatment.
                                summary
    The NIH investment in AIDS research has produced groundbreaking 
scientific advances that have benefited not only patients with HIV, but 
those with other diseases as well. For example, the development of 
protease inhibitors to treat HIV has led to development of a new drug 
combination that can cure hepatitis C, which affects about 150 million 
people globally. That advance in hepatitis C research may, in turn, 
provide important knowledge toward an HIV cure. Drugs developed to 
treat HIV-associated opportunistic infections are benefiting the more 
than 28,000 Americans who receive an organ transplant each year. 
Research on HIV-associated neurologic and cognitive manifestations 
ultimately will benefit millions of patients with Alzheimer's disease 
and other aging and dementia issues.
    Despite these advances, however, AIDS is not over, and it is far 
too soon to declare victory. Serious challenges lie ahead. The HIV/AIDS 
pandemic will remain the most critical public health crisis of our time 
until improved and affordable prevention and treatment regimens are 
developed and universally available. NIH will continue to search for 
critical solutions to prevent, treat, and eventually cure AIDS.
    Thank you for your continued support for these efforts.

    Senator Harkin. Thank you very much, Dr. Collins. We will 
start a round now of 5-minute questions. As I said at the NIH, 
I have never come away from a conversation or listening to you, 
Dr. Collins, without being more enlightened and more hopeful 
about the future. I like that ``National Institutes of Hope.''
    Let me just ask you a question about the BRAIN Initiative, 
if I can start with that. I have got two or three questions on 
the BRAIN Initiative. Paint for me a picture of how you see the 
research going ahead in the BRAIN Initiative. And we have some 
partners, four outside partners, right now that are also 
putting money into this, and you have an advisory group from 
DARPA (Defense Advanced Research Projects Agency) and NSF 
(National Science Foundation). Paint for me the picture of how 
you see this developing in the next 2, 3, 4, 5 years. And sort 
of what do we hope to get from this?

                            BRAIN INITIATIVE

    Dr. Collins. Well, we are enormously excited about this, 
and I am going to ask my colleague, Story Landis, who is a 
major leader at NIH in the BRAIN Initiative, to say a word. But 
just very briefly from my perspective, this is one of those 
moments that comes along once in a long time where the 
technology to be able to tackle a truly important problem, 
understanding how the circuits in the human brain work, has 
arrived at the point where we have this kind of push, bringing 
disciplines together that have not necessarily found each 
other, and making this a priority. We believe we can transform 
our understanding of this incredible organ with its 86 billion 
neurons, each of which has maybe a thousand connections. But, 
Story, say where we are and where we are going.
    Dr. Landis. So we are very excited about the opportunity to 
really understand how neural circuits in the human brain work--
86 billion neurons, each of which are connected in complicated 
circuits and pathways that process information, that allow us 
to see an image and interpret it, to hear words and understand 
what they mean, to remember, to reason.
    We have some understanding now of how those 86 billion 
neurons are organized into circuits, but we do not nearly have 
enough detail, and we do not know enough about how information 
is processed. And the goal of the BRAIN Initiative in the first 
five or so years is to really develop the tools that will allow 
us to probe those questions. There will be early on potential 
opportunities to translate to disease, and I could give you 
some examples if you would like.
    Senator Harkin. Let me ask you this, Dr. Landis. Are you 
working with the National Institute on Aging? Is there any 
connectivity between the BRAIN Initiative and Alzheimer's 
research?
    Dr. Landis. Absolutely, although the understanding that we 
will gain from the BRAIN Initiative will then be applied to 
understanding how circuits are perturbed in Alzheimer's. 
Alzheimer's disease nerve cells die. We would like to prevent 
that death, but in the absence of tools yet to do that, the 
circuits reorganize when cells are lost. And the BRAIN 
Initiative will give us a better understanding of why that 
reorganization occurs and how we can potentially use the 
neurons that remain to have much more function.
    Senator Harkin. Well, I asked that because, you know, we 
have a lot of things confronting us in the future. I will get 
to Dr. Varmus and cancer. But if we do not do something about 
Alzheimer's, that is a tsunami that is going to hit us big 
time. And so I just really wanted to get that on the record 
that the money that we are putting into the BRAIN program, 
BRAIN research program, also has a connectivity to Alzheimer's 
research.
    Dr. Landis. Absolutely.
    Senator Harkin. Okay.
    Dr. Collins. Think of the BRAIN Project as a foundation for 
all neurological diseases, just like the Genome Project was a 
foundation for all genetic diseases. It lifts all of those 
boats of research to go higher and faster.
    Senator Harkin. Sure.
    Dr. Landis. And psychiatric diseases and drug abuse, all 
the brain disorders.

                       FUTURE OF CANCER RESEARCH

    Senator Harkin. Exactly. Dr. Varmus, again, I would be 
remiss if I did not thank you for a lifetime of devotion and 
dedication to biomedical research, stewardship of the NIH for a 
lot of the time I was either chairman or ranking member. And it 
is good to have you back as the head of the National Cancer 
Institute.
    Here is my question: What excites you the most right now? 
In all of cancer research and stuff, what is it that gets you 
up in the morning right now that you are looking ahead to do?
    Dr. Varmus. Thank you. And before I give you a brief answer 
to that question, let me first of all compliment you on your 
service. You and I have been facing each other across the dais 
like this for 20 years off and on, and I have always admired 
your passion, your commitment to the NIH, your honesty. And 
even on those rare occasions when we disagreed on a few issues, 
we have had a collegial and constructive relationship. And your 
departure from this Congress is a heavy blow to the NIH and to 
its supporters.
    Senator Harkin. I appreciate that.
    Dr. Varmus. What most excites me at the moment is the deep 
intellectual understanding we have about how cancer arises and 
how the body tries to respond to it. And the connection between 
basic science and its very near apposition to what we can do 
practically is thrilling.
    Over 40 years ago, I have to confess when I began doing 
cancer research, the application of what we were trying to 
learn with chicken viruses and mouse viruses was very far away. 
Today we use tools of genomics and immunology and biochemistry 
in a way that is very closely connected to what we are doing in 
the clinic. So when we discover a new gene that is involved in 
cancer, it is not long before we find some drug, perhaps an 
existing drug, that can be applied to patients whose tumors are 
being analyzed with the instruments of genomics to identify 
exactly what is wrong with that cancer, and to carry out in a 
precise fashion a clinical trial that is designed in entirely 
new ways.
    Similarly, we have learned from basic immunology the kind 
of thing that Dr. Collins just illustrated is also being 
applied in immediate ways to try to interfere with the breaks 
on the immune system that have kept the immune system from 
attacking cancer cells.
    Senator Harkin. My time has run out, but I will have a 
follow-up on that on immunotherapy and Dr. Rosenberg and what 
he is doing out there. Okay.
    Senator Moran.

                          ALZHEIMER'S DISEASE

    Senator Moran. Mr. Chairman, thank you very much. Dr. 
Collins, Dr. Landis, and others, thank you very much for 
attending the recent hearing we had in regard to Alzheimer's in 
particular. Several members asked that day if we would reach 
the goal of a cure for Alzheimer's by 2025 and how much money 
it would take to do so.
    I understand how difficult it must be to quantify such an 
answer, but I think it is important for us to know if our 
Alzheimer's research funding is on track. Therefore, I am 
looking for your professional opinion or opinions as to how 
much money does NIH need in fiscal year 2015 to keep pace with 
the goal of a cure for Alzheimer's by 2025.
    Dr. Collins. Well, thanks for the question, Senator, and 
that was an excellent hearing that was held by this 
subcommittee. And we had a great opportunity there to look at 
the challenge and also the scientific opportunities, which are 
really coming forward in very exciting ways, recognizing that 
the challenge here in terms of both the economic and human cost 
of this disease can hardly be overstated.
    As you have pointed out, we have an action plan for 
Alzheimer's disease, part of the legislation that put in place 
this project--plan. And the National Institute on Aging, 
directed by Dr. Hodes, has been deeply engaged in that, running 
a research summit at NIH, and polling the entire community 
about where the research opportunities would be. It is 
wonderful that in fiscal year 2014, largely due to this 
subcommittee's efforts, $100 million has been appropriated for 
the National Institute on Aging, the bulk of which will be put 
into promising Alzheimer's research.
    I have looked carefully at the way in which the Alzheimer's 
plan maps across the various years. As you know, science tends 
not to operate in 1 year intervals. Many of the components of 
the plan are more in a 3-year kind of timetable. I could show 
you a Gantt chart that goes on for many pages about how each of 
these components might start and hopefully reach a milestone.
    It is very difficult, though, with all the multiyear aspect 
of this to say, well, what do we need exactly in fiscal year 
2015? And I have sort of tried with Dr. Hodes to come up with 
that kind of estimate, and I am afraid it would not be a 
reliable one. Part of that is, of course, we do not have the 
ability in science to know exactly what is going to happen next 
month or the month after that. And a lot of the research in 
Alzheimer's is being developed by investigators out there in 
our wonderful brain trust, the universities that are doing this 
research. And we might wake up tomorrow and find that something 
has happened that completely changes the direction we want to 
go. So while this plan is a good one to work with, it will 
undoubtedly evolve over time.
    So I know I am sounding like I am not giving you an answer, 
and I guess I am trying to say I think to put a dollar figure 
right now on fiscal year 2015 would be to overstate what I 
really can predict to be necessary for this purpose. Again, we 
are thrilled with $100 million in 2014. We were delighted to 
see in the President's Opportunity, Growth, and Security 
Initiative another $100 million would come to Alzheimer's 
disease should that become possible.
    Senator Moran. You have the capability, Dr. Collins, I 
assume, of telling us or telling me that the $100 million in 
fiscal year 2014 was not too much.
    Dr. Collins. It was not too much. You are quite right about 
that. And, you know, you are asking about Alzheimer's. You 
could be asking about many other areas of NIH research as well, 
and I would tell you we do not have too much money to work on 
anything that we are working on. We are not limited by ideas. 
We are limited by resources, whether it is cancer, infectious 
disease, heart disease, whatever. That is our current state.
    Senator Moran. Doctor, let me take this question in a 
broader step. But first let me say that my expectation would be 
as those scientific developments occur, a reason that we should 
have the kind of hearings that we have on an ongoing basis is 
so that you can then come to us and say this development has 
happened in some university in the country or here at NIH. And, 
therefore, if you would invest additional dollars in this area, 
we believe we can advance the outcomes more quickly.
    And so, my continued effort, I think, will be to try to get 
you to help us prioritize spending based upon science, based 
upon success in research where we ought to put the dollars that 
we have to allocate within the 27 Institutes and Centers that 
you and NIH engage in.
    Dr. Collins. Senator, I would welcome those kinds of 
conversations at any time, and appreciate your leadership in 
that kind of planning process.

                        DISEASE SPECIFIC FUNDING

    Senator Moran. I have 28 seconds left for a follow-up 
question, which is this: You have--you, NIH--has historically 
opposed disease-specific funding. You want the allocations to 
occur based upon science, not on politics, and I certainly 
share that goal. If we are underfunding in an area of 
research--if we start with low funding in a particular area of 
research, it is harder to have the developments that then allow 
you to come to us and say we have had a breakthrough, we need 
more. We need to accelerate the funding of that research.
    How are you--I mean, can you give me examples--I do not 
have the history that Senator Harkin has, but does it happen 
from time to time in which you come to Congress and say we need 
to prioritize the research in this area, and are you willing 
then to tell us that we reduced the priority someplace else? 
How do we ever get into the circumstance in which any of us are 
willing to say our money should go into this basket, knowing 
that it is not infinite? The money has to come out of some 
other basket.
    Dr. Collins. Well, again, I appreciate the question. And 
this is the kind of conversation we have around the table at 
NIH all the time with the 27 Institute and Center directors, 
each of whom has a strategic plan that they are constantly 
refreshing and revising.
    The good news is that the boundaries between those 
institutes are very porous. And if we collectively identify an 
opportunity that demands additional investments in a particular 
direction, we often can figure out how to do that without 
having to go through a long lead time to try to adjust a future 
year's budget. And we are quite capable of doing so.
    And increasingly, that is a good thing because the next 
breakthrough in cancer might come from the Diabetes Institute, 
and the next breakthrough in infectious disease might come from 
the Center that is looking at translational sciences. So we are 
really, more than we ever have been, a unit, a whole here that 
thinks about biomedical research collectively, not in a series 
of buckets.
    Senator Moran. Thank you very much.
    Senator Harkin. Thank you, Senator Moran. And our 
distinguished Chair of the entire Appropriations Committee, who 
happens to have a real interest in NIH, I can tell you that.
    Senator Mikulski.
    Senator Mikulski. Thank you very much, Senator Harkin, and 
we are so glad that you are holding this hearing. And I think 
it shows the significance of the way we think about the 
National Institutes of Health, which we all affectionately and 
with great admiration do call the National Institutes of Hope. 
The fact that Senator Shelby is here, the vice chairman of the 
Appropriations, and myself shows our commitment to really 
trying to make sure that NIH has the resources it needs to 
continue to be the premiere global agency for biomedical 
research, and to do it on a bipartisan basis.
    I know you spoke earlier, if I could. You were kind of 
emotional about this hearing, and I am emotional about this 
hearing for you. I recall coming to the United States Senate. I 
was sworn in 1987, working with then the beloved Nancy 
Kassebaum, you, and Ted Kennedy, when women were not even 
included in the protocols, many of the research things, at NIH. 
There were many reasons. Many were just flawed sociology rather 
than good biology.
    Imagine in those years when we were not even included, and 
then we advocated for the Office of Women's Health. The funding 
then for breast cancer was quite spartan and skimpy. Again, we 
turned to you. And then as we made steady advances, George 
Herbert Walker Bush appointed Bernadine Healy to be the head of 
NIH. Dr. Healy also reached out again to us to ask us to look 
for a famous longitudinal study on hormone therapy. That 
hormone therapy study resulted in the change in the way 
hormones are treated in terms of hormone therapy for women, and 
it resulted in breast cancer coming down by 15 percent.
    I recall with great emotion my last call with Bernadine 
Healy, and this is what she said. I called her, and there was 
an article in the New York Times, Dr. Varmus, that said breast 
cancer rates have come down 15 percent. And I said, ``My god, 
Bernadine, can you believe that?'' She said, ``Yes, Barbara. 
Can you believe because we worked together we are saving lives 
a million at a time?''
    That is what we are trying to do here with this hearing. We 
are trying to look at these issues. And I am going to say to 
you, Senator Harkin, the Catholic nuns had a phrase when they 
taught people like me. They had a phrase in Latin called 
``exegi monumentum aere perennius aedificabo.'' It means we 
will build a monument more lasting than bronze. I feel our 
monument to you, to both you, to Senator Specter, to Bill 
Frist, Ted Kennedy, is the way we walked across the aisle is to 
build a monument more lasting than bronze, and that is to make 
a significant public investment this year in the National 
Institutes of Health to get it right back on track to where it 
was, and to have a steady growth plan of action so that at the 
end of the day, at the end of the year, at the end of our 
terms, we know that we have been working together to save lives 
a million at a time. So I want to just shake your hand and 
thank you. And, Moran, you are from Kansas.
    Senator Moran. Yes.
    Senator Mikulski. You know what Nancy did shoulder to 
shoulder here. Senator Shelby has been a great advocate.
    I have many questions that I am going to ask. We could hold 
a hearing on each and every one of those people--distinguished 
people here. We are lucky to have them. Their combined years of 
service are stunning. Many of them at this table could be in 
such lucrative careers in the private sector.
    I remember working with Dr. Fauci when there was this 
unknown disease in which men were dying all over the country. 
It was called AIDS. A little boy named Ryan White came here 
with his mother when he had been targeted by his classmates for 
taunts and isolation. Now look at where we are. We could take 
item after item, issue after issue, and it really shows what we 
need to do.
    So we need to not only fund the research, we need to 
support the people who do the research. And to those young 
people out there right now thinking about careers that there is 
hope in trying to find cures to give people hope. And so, this 
is where we really need to work on a bipartisan basis, hands 
across the aisle, hands across the dome. And I think we can 
make a significant difference. So we want to help build a 
monument more lasting than bronze.
    I yield back my time.
    Senator Harkin. Thank you very much. That was a very 
poignant statement, and I thank you for that. The only thing I 
would add is we have to come to grips with the funding, and I 
am open for any and all suggestions.
    Senator Mikulski. I know we are all going to get into this.
    Senator Harkin. I just met yesterday with a couple of 
people who had an interesting idea on funding for translational 
science. Gordon Gund and Karen Petrou from the Foundation for 
Fighting Blindness have come up with--I do not need to go into 
that now, but there are ideas being spawned out there on how we 
might raise more money for NIH. So anybody that has got 
suggestions, we need to keep looking.

                      PREFERRED METHOD OF FUNDING

    Senator Mikulski. And, Mr. Chairman, if I could, if Dr. 
Collins could comment. We had a great hearing on Alzheimer's, 
and also that is an epidemic in our country, as is autism, 
quite frankly. And again, many here could comment on it. And 
then there are those things that seem benign and not too scary, 
but then along comes flu. But when we look at the ``A'' words--
autism--there was talk of, like, do we need, like, a Manhattan 
Project.
    And I wonder to Dr. Collins and the esteemed panel, what is 
it that is the best thing for NIH, sustained, steady growth 
with kind of an agreement across the aisle and across the dome 
of steady increases to the way we had the concept of--I 
understand if we added--kept pace with inflation at 3 percent, 
and then another 5 percent, we could get to almost doubling 
NIH--we do not want to use that phrase anymore--to $40 billion. 
Is that better rather than a concentrated big buck expenditure 
on one particular area for----
    Dr. Collins. I really appreciate the question. And I wanted 
to show you a graph----
    [The graph follows:]

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
    

    Senator Mikulski. In other words, does the idea of a 
Manhattan like project really have efficacy, or does it sound 
good, but----
    Dr. Collins. What you see on the screen here is the 
projection over the past years since 1990 of the NIH support 
corrected for inflation because we have to deal with that. That 
is the yellow line. You see the blue bar is there for the 
Recovery Act, those 2 years of an increment which helped with 
sort of pent-up need.
    But notice the doubling, which happened there between 1998 
and 2003, then encountered essentially flat budgets, which 
inflation has eroded ever since. And you can see interestingly, 
the dotted line is the trajectory we were on before the 
doubling, which if you go back to 1970, we were on a period of 
about 3.7-percent annual growth. If we had stayed on that 
steady trajectory, we would now be $10 billion almost higher 
than we are. Very interesting to sort of contemplate this.
    Now, the doubling was wonderful. The doubling did huge 
things for biomedical research. But what came after has been 
really quite painful. And to answer Senator Mikulski's 
question, the worst thing you can do, I think, to biomedical 
research is to create an area of uncertainty, of ups and down, 
of a roller coaster. Science operates not as a spring, but a 
marathon. You need confidence that there is going to be support 
there so that young scientists can tackle really innovative 
risky projects. And this up and down circumstance now hitting 
historic lows in terms of opportunities to get support is 
really quite damaging.
    And what would be vastly better, Senator, would be for us 
to be able to count on a more or less stable trajectory of 
inflation plus some percentage that you could be fairly 
confident was going to be maintained. I understand how hard 
that is in the current fiscal situation, but if you are asking 
my judgment about what NIH needs in order to flourish and in 
order to contribute to this Nation what we think we can 
contribute and to the world, that would be it, that kind of 
steady trajectory that you could be confident in.
    Senator Harkin. Thank you, Dr. Collins. Senator Shelby, our 
ranking member of the entire committee. Used to be the ranking 
member of this subcommittee.
    Senator Shelby. Thank you. Thank you, Chairman Harkin, and 
thank you for all your service here and advocacy for NIH. I 
believe as a veteran member of the Appropriations Committee 
looking at all the aspects of the various requests for money 
that the NIH, I think, by far is the best investment we have 
made. And we should make sure that it is properly funded and 
not let it be eaten up with inflation.

                 ECONOMIC IMPACT OF BIOMEDICAL RESEARCH

    Dr. Collins, tell us the economic impact of biomedical 
research, including pharmaceutical research--NIH is the leader, 
but going on elsewhere, too, in the private sector--in this 
country, and how important is it not to just our health, but to 
our economy and our leadership in the world. You have some 
numbers there?
    Dr. Collins. I have some numbers. I could go on all day 
with numbers because----
    Senator Shelby. How about taking a few minutes?
    Because the chairman will gavel----
    Dr. Collins. I will try to rein it in here.
    Senator Shelby. Thank you.
    Dr. Collins. I will tell you when I came to this job to be 
Director of NIH, I did not realize how important it was going 
to be to have this kind of case in front of the public and in 
front of the Congress in order to justify what we are doing 
because the main reason I am excited about being at NIH is the 
advances in research that are going to help people. But there 
is another great story here, which is that every $1 that we 
give out in grants to all 50 States, by most estimates, returns 
more than two-fold in terms of economic----
    Senator Shelby. It is a huge multiplier, is it not?
    Dr. Collins. It is about $2.21 per $1 according to one----
    Senator Shelby. In GDP (gross domestic product) and jobs, 
right?
    Dr. Collins. And in jobs. We directly support about 432,000 
jobs through our grants. But if you figure out how NIH is sort 
of part of the ecosystem that creates jobs in biotech and in 
pharma, the estimate is something like 7 million jobs are 
dependent upon the progress that NIH makes, and are somewhat 
jeopardized by our current circumstance.
    And when you look at the competition issue, which is 
another one that people raise, certainly America has led the 
world in biomedical research for the last 20 or 30 years, but 
that is gradually eroding, and, in fact, eroding more quickly 
these days, especially after sequester. And if we are 
interested in seeing those kinds of returns like were talked 
about with the Genome Project, a 141 to 1 return on those 
dollars, do we really want those returns to go somewhere else, 
or do we want them to happen right here?

                          AUTOIMMUNE DISEASES

    Senator Shelby. Absolutely not. We want to keep it here. 
Let me ask you a question. I am limited in time. We have a 
chairman with a good gavel here. In the autoimmune area that I 
have worked with you before, rheumatoid arthritis and lupus, 
are you cutting back on the money there? It seems like you are. 
And if so, why?
    Dr. Collins. We are only cutting back because we have to 
cut back everywhere.
    Senator Shelby. Because of lack of money.
    Dr. Collins. Even with the wonderful things you all did 
with the fiscal year 2014 omnibus, we did not recover 
everything we lost in the sequester. I will say one bit of good 
news about lupus is the development of this partnership with 
industry called the Accelerating Medicines Partnership, AMP, 
because lupus is one of the targets that we are going after.
    Senator Shelby. They are kind of matching you on money, 
right?
    Dr. Collins. They are, $230 million over 5 years, half of 
it from us, half from them, and bringing scientists around the 
same table who would not normally be talking to each other, and 
having this all done in an open access fashion. This is an 
interesting experiment, but it may very well get us that next 
generation of drug targets for lupus.
    Senator Shelby. Doctor, how important is not just for 
lupus, but all the autoimmune diseases--the whole spectrum 
affects so many of the areas of research that you are working 
on, does it not?
    Dr. Collins. Absolutely, and maybe Dr. Fauci would want to 
say a word about this since he is the most distinguished 
immunologist in the room.
    Senator Shelby. We know.
    Dr. Fauci. Thank you for the question, Senator. Indeed, I 
think the issue with autoimmunity is really an example of how 
fundamental basic research and understanding how the immune 
system is regulated over the last several years have provided 
extraordinary insight into how we can better manage, diagnose, 
and ultimately treat, and in some cases even prevent, 
autoimmune diseases.
    Whenever you think about autoimmunity, the terminology 
itself is descriptive, namely an immune response against 
oneself that is inappropriate, and that is what is studied at 
the very basic level. At the NIH, we now are developing 
consortia where, as you hinted, multiple institutes are 
involved in immunology--the Cancer Institute, the Heart, Lung, 
and Blood Institute, our institute, the Arthritis 
Musculoskeletal and Skin Diseases Institute, et cetera. They 
all are, and we have a consortium now----
    Senator Shelby. Immunology kind of transcends it all, does 
it not?
    Dr. Fauci. It is one of those disciplines that essentially 
touches to a greater or lesser degree virtually everything we 
do.

                            CYSTIC FIBROSIS

    Senator Shelby. Dr. Collins, in another area--my time is 
limited, just a few seconds--but cystic fibrosis. We have come 
a long way there. We are a long way from a cure, but we have 
extended a lot of the children's lives, you know, beyond, gosh, 
what we thought. Where are we today, and what are some of the 
hopes there?
    Dr. Collins. Well, cystic fibrosis is a wonderful example 
of how knowing the molecular basis of a disease can get you to 
a point with a great deal of hard work to a targeted 
therapeutic that is not just hoping something will work, but 
designing it to work.
    So cystic fibrosis, where my lab had the privilege of being 
involved in that and found the gene in 1989. Just a year ago, 
the first really effective therapeutic for about 5 percent of 
cystic fibrosis patients that have a particular mutation in 
that gene was approved by the FDA, infact. And it is truly 
dramatic the stories you hear from those individuals. I have 
heard stories of kids who were on the lung transplant list who 
are now not on it anymore.
    The main challenge now is to find an equivalent therapy for 
the majority of cystic fibrosis patients that have a different 
mutation, the so-called Delta F508, and there is a clinical 
trial very actively underway by Vertex. The drug is called VX-
809. We are all holding our breath to see what the results of 
that will look like. The initial glimpse with a smaller phase 
two study looked pretty promising.
    So you have gone--it took a long time. And one of the 
things that NCATS, and my colleague here, Dr. Austin, is 
charged to do is to try to shorten what would be a 20-year 
timetable into something much faster. But the pathway here that 
was charted by cystic fibrosis in a collaboration with the CF 
Foundation that was a major partner here is truly exciting. It 
is a paradigm. We could do this again.
    Senator Shelby. Thank you very much for the work you do. 
Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Shelby.
    Senator Kirk.

                        REHABILITATION STANDARDS

    Senator Kirk. I want to ask Story a question as a stroke 
survivor. We have two members--senators on this committee who 
are stroke survivors. I would like to take you into the world 
of our rehab standards, which Senator Johnson and I have both 
introduced legislation, S. 1027, to speak on behalf of the 
900,000 Americans who will survive stroke we expect this year. 
We know that roughly one-third of them will never return to 
work. And Tim Johnson and I have a belief that we could set a 
national standard of returning those stroke survivors to work. 
That would unlock a hell of a lot of Americans to pay taxes and 
be productive.
    Let me just burrow in for rehabilitation standards. My 
understanding is out of the $3 billion NIH, about $66 million 
is spent. I think the country would do well to have NIH 
establish a rehabilitation standard.
    Dr. Landis. So, NINDS (National Institute of Neurological 
Disorders and Stroke) recently established a stroke network of 
clinical centers that will undertake stroke trials. And one of 
the major reasons we did this was to have a balance in our 
investment in prevention, acute treatment, and stroke 
rehabilitation. We have recently finished one trial, which has 
shown that it is not--never too late to start rehabilitation 
for stroke, that significant gains can be made even after 6 
months. We have another trial underway. But this has clearly 
been an area where there has not been sufficient investment, 
and this clinical trials network will enable us to do more 
trials better and faster, which will create the kind of 
standards that you are asking for.
    Dr. Collins. Could I add one thing, that the number you 
mentioned is the funding for the National Center for Medical 
Rehabilitation Research, NCMRR, which is actually within the 
National Institute of Child Health and Human Development. But 
that is not the sum total of all that we spend on 
rehabilitation research. Much of what Dr. Landis was just 
talking about is in a different part of the budget. So the 
total expenditures on rehabilitation research are several times 
that number, just to clarify.

                          JOHN PORTER MEMORIAL

    Senator Kirk. Thank you, Mr. Chairman. I just wanted to--
could I follow up and thank you for honoring my political 
mentor, Congressman John Porter, the other day, the man who on 
a bipartisan level led to the doubling of funding for this 
institution. You guys honored a great man who really put 
together an awesome team with Speaker Gingrich on that.
    Dr. Collins. And, Senator, let me thank you for sending a 
wonderful video that the 400-some people who were there for 
that dedication watched and were touched by. And I appreciate 
very much your contributing to our event. This was a grand 
moment for NIH.
    Let me say one other thing about rehabilitation research. 
We are very much in the process now of seeking a new director 
for this National Center for Medical Rehabilitation Research, 
someone who will be particularly forward looking in identifying 
opportunities, how to work with the institutes, how to build 
the case here for rehabilitation research to be even more 
vigorous than it has been. And we are looking for the very best 
person on the planet to do that.
    Senator Harkin. Thank you very much. We will start another 
round.

                   FUNDING HISTORY AND SUCCESS RATES

    Dr. Collins, do you still have that chart that showed where 
that doubling was? You showed that line for the constant 
inflationary increase of, I think it was $3.7 or something. 
That one right there.
    [The graphic follows:]

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
    

    Senator Harkin. Again, just for the record--there may be 
people who were not here at that time. Here is how we came 
about that doubling. In the 1990s, we saw the rate of approval 
of grants percentage going down and down and down from what it 
had been in the 1980s.
    And so, meeting with people at the Institute then--it was 
Dr. Varmus at that time, if I remember right, others. We were 
talking about what would it take to sort of get back up to that 
level where we were in the 1980s for the percentage of--what is 
the phrase I am looking for--grant approvals, right?
    Dr. Collins. Success rate. Success rate.
    Senator Harkin. Yes, success rate. And so, we got that. And 
what that would take would be--what it meant was to double the 
funding over a period of 5 years. Our thought was that once we 
did that and got up there, that blue would then start up there 
where the top was, and we would go on----
    Dr. Collins. That is what we were hoping for, too, believe 
me.
    Voice. The soft landing.
    Senator Harkin. This was never meant as some transitory 
type of a funding bump. Now, maybe the Recovery Act was. That 
was sort of a transitory bump, but the doubling was to get us 
back up to that level and then continue on.
    Dr. Collins. Yes.
    Senator Harkin. And so, we sat here through the 2000s and 
saw what happened. Again, I do not mean to speak politically, 
but just factually. We had two wars going on. 9/11 had 
happened. More and more money was being siphoned off for that. 
I am not making a judgment call on that. That is just what 
happened. And we were in a situation where we were not raising 
revenues, but more and more money was going for the War on 
Terrorism, and that is what happened. We just did not have the 
resources, and we came back down, and that is where we are 
today.
    It pains me, and it pains a lot of people to think that 
that happened. We deliberately did that to get that line back 
up there and to keep it going. And, well, other things 
happened, and so we are back in this situation now, and we are 
scrambling to find the resources that we need to do this. We 
need more revenues. That is just my own thing. We need revenue. 
I think the taxpayers of this country would not mind paying a 
little bit more in their taxes or the wealthy or the 
corporations, everybody, to know that this was going to help 
NIH and that is where the money was going.
    And so, somehow we have just got to get the revenues in for 
this, and like I said, I am open for any other thoughts and 
suggestions on how to do it. Senator Hatfield at one time had 
an ingenious idea of doing that. I joined him in that. That did 
not get very far, but it was a proposal that we would take, I 
think it was 1 cent out of every $1 that went for healthcare 
premiums. See, a lot of people do not know that when you go to 
a drugstore and you buy a prescription, and when you get a 
prescription drug or something like that, some of that money 
goes for research. But we do not do that in our healthcare 
policies. When you buy a healthcare policy, none of that goes 
for research.
    So the idea that Hatfield came up with was that 1 cent out 
of every $1 that would be--go into a fund that would come to 
this committee. That would go to NIH as long as we funded NIH 
at last year--at the previous----
    Senator Mikulski. Maintenance of effort.
    Senator Harkin. Maintenance of effort, thank you. That 
phrase, ``maintenance of effort,'' then that money would be 
available to NIH. That would have been a great deal to have, 
but we did not get it. And I am still thinking that there is 
something out there in that realm of healthcare policies where 
people who are buying healthcare policies would say, ``Yes, I 
would like to have a half a penny or something go to biomedical 
research and come into a fund.'' I think people would support 
that if they knew that is where it was going. It was going to 
NIH. They would support that. So I have not quite totally given 
up on that idea, but there may be others.

                       RETIREMENT OF CHIMPANZEES

    Dr. Collins, I have one other question I want to ask sort 
of off of what we have been talking about here, but it is one 
that I hear a lot of about, people keep asking me about. There 
is a great interest in this country about what is happening to 
our chimpanzees. As you know, we have had a great partnership 
with you, with the Humane Society, on retiring these 
chimpanzees from research.
    I know Senator Landrieu has been kind of in the forefront 
of this, and I know she wants me to also ask this question. I 
was one of three Senators who requested the IOM (Institute of 
Medicine) report that revealed that chimpanzee research could 
not be justified except for a very few conditions. Again, Dr. 
Collins, you are to be commended for adopting the IOM 
recommendations so promptly, the very day the report was 
released. Your decision to retire approximately 310 of the 360 
Government-owned chimpanzees currently in laboratories was a 
bold maneuver, and I thank you for that.
    As a long-time appropriator, however, I know that the work 
takes far longer than the issuing of a policy or the signing of 
a bill. I am keenly aware of the complexity of creating 
sanctuary space, grouping, transporting chimpanzees, arranging 
for their care. Many of these chimpanzees suffer from illnesses 
and conditions we gave them for the sake of research. So could 
you please update the subcommittee on the plan for retiring 
these chimpanzees? Can you highlight the challenges and 
considerations involved, including any funding challenges that 
we need to be cognizant of?
    Dr. Collins. Well, thank you, Mr. Chairman, and thank you 
for your leadership on this issue in many steps along the way, 
including asking the IOM to conduct that study, which concluded 
that the need for chimpanzees in research had now been greatly 
reduced and that we could, in fact, get by just fine by keeping 
a small group of 50 available for emergency needs or special 
things where only chimpanzees could be used for research.
    And you also helped us with a fix on what had been a 
legislative problem about a cap on the amount of funds that NIH 
was allowed to spend on chimps in sanctuaries, and that made it 
possible for the retirements that we very much wanted to go 
forward. But you are quite right, we have a long way to go here 
in terms of the number of chimps that need to be moved into 
sanctuaries. And at the present time, that space does not 
exist.
    We have moved many already into Chimp Haven, which is 
already now pretty close to capacity. We are looking vigorously 
at other----
    Senator Harkin. Is that the one in Louisiana?
    Dr. Collins. Yes, and we are vigorously looking at other 
alternatives because there are other chimp sanctuaries to make 
sure that they meet the standards that you would want to see so 
these chimps are well cared for. And there is much interest in 
philanthropy in helping out with this, and the Humane Society 
has been a wonderful partner as well. My dear friend, Jane 
Goodall, who will turn 80 years tomorrow, has been very helpful 
in raising the consciousness of everyone about what an 
important issue this is.
    I would not tell you that we have this solved. I think it 
is going to be several years before the space can be 
identified, the funds can be found, and the completion of the 
retirements can be achieved so that we are left with just those 
50 chimps for research. And we will be re-evaluating that 
regularly as well to see whether those are even needed at that 
level. But I appreciate your interest and this committee's 
interest in this, and we are going to keep you regularly 
briefed on what the needs might be.
    Senator Harkin. This started back in the late 1990s, and 
that is when Jane Goodall came to see us. And Senator Bingaman 
I know was involved. The Senator on the Senate side that 
introduced the bill on saving the chimps was Senator Bob Smith 
from New Hampshire. I remember that. I forget who the other one 
was, but there was a strong bipartisan effort. And so, it has 
taken a long time. I know we got that cap removed. It was a $30 
million cap if I am not mistaken. We got that removed.
    Dr. Collins. Yes. Yes.
    Senator Harkin. But there is a great deal of interest in 
moving ahead on this. And maybe if you cannot today, could you 
get to the committee sort of the timelines you see and what 
more do we need to do to kind of expedite this?
    Dr. Collins. I am glad to do that.

    [Clerk's Note: The information requested can be found in the 
``Additional Committee Questions'' for Senator Harkin.]

    Dr. Collins. And, Mr. Chairman, again, when I came to this 
job as NIH Director, I did not imagine that this issue would 
become so prominent. And yet it has turned out to be, I think, 
one of the more gratifying opportunities to work across many 
different constituencies and do the right thing for these 
special animals, who are our closest relatives.
    Senator Harkin. Our closest cousins.
    Dr. Collins. Absolutely.
    Senator Harkin. Thank you very much.
    Senator Moran.

                     DISEASE FUNDING PRIORITIZATION

    Senator Moran. Chairman, again, thank you. Dr. Collins, I 
am going to ask one more question about prioritization, and 
then a couple of questions for a couple of your directors.
    What are the criteria--when you say this is an ongoing 
conversation about how to prioritize funding within NIH among 
the various diseases--that you look at? Is it the likelihood of 
success, the next opportunity for a breakthrough? What role 
does it play about the cost of the disease? How many people are 
afflicted, what the cost of care and treatment are? Is it a 
more scientific exercise in trying to prioritize how to spend 
money correctly, or is it a broader concept that you pursue?
    Dr. Collins. That is a great question, and it is something 
that we work on every day. It is a mix of all those things. 
Certainly the public health impact has to be a concern for us, 
the number of people affected, and the severity of the illness, 
and what it does in terms of quality of life or premature 
death. Those are all factored in. But if we only thought about 
those things, then rare diseases would get neglected, and we 
have learned so much from studying rare diseases. And if it is 
your family, it does not matter so much to you that it is a 
rare disease than if it is your child who is suffering from it.
    We also think about scientific opportunity because that has 
got to be a major reason to decide to make a push in a 
particular direction, that something is emerging that is 
possible and maybe it was not a year or two previously, and you 
do not want to lose the opportunity to push forward on that.
    On top of that, of course, a lot of our portfolio is not 
top down managed, and it should not be. It comes from the 
insights, the ingenuity, the creativity, the bold vision of 
those investigators out there and the universities across this 
country who are remarkable in their abilities to think of 
things that we could not have thought of. And, we, therefore, 
have a very substantial fraction of our portfolio that is not 
targeted or directed based on anybody's idea about public 
health need or about scientific opportunities other than the 
fact that they are proposing something scientific. Those then 
go through a peer review process. If the idea does not measure 
up, it does not make it into the next tier.
    I would tell you, though, that peer review, while it is 
critical, it is not the only part of what we do. And all of the 
Institute directors you see here, once we have had the peer 
review, look across that, and the things that are somewhere 
near the pay line, decide what is the highest program priority 
based upon the issues that I just talked about--public health 
need, scientific opportunity--and also is our portfolio well 
balanced, or do we have a big pile up of things in one area and 
neglect in other areas. All of that calculus folds into this 
every day that these institute directors and I are struggling 
with. And I think we do a reasonable job of it, but we are 
always trying to do better.

              NATIONAL CANCER INSTITUTE COMMUNITY PROGRAMS

    Senator Moran. Thank you for your answer. Dr. Varmus, NCI's 
budget request includes information on expanding access to 
clinical trials for patients treated in community settings and 
expanding access to trials by minority and underserved 
populations. One of those underserved populations is rural 
Americans, and I was interested in knowing if you could talk 
about the goals of that program and how many new NCI community 
oncology research programs, projects you might expect to find.
    Dr. Varmus. Well, Senator, I cannot give you an exact 
number for that, but as you were rattling off the names 
suggested, you are aware that we have just amalgamated two of 
our community-based programs into one called NCORP for 
Community Oncology Research Program, in which we are paying 
special attention to minority populations and rural populations 
and trying to bring hospitals that are not in our NCI 
designated cancer centers into the network of organizations 
that organize our clinical trials and provide more patients. 
And indeed, many of these centers that compete particularly 
effectively for money to support clinical trials have been in 
these areas--have been producing large numbers of patients to 
accrue them into our trials over the last several years. That 
is an important factor in making a decision about who will get 
support.
    As you know, we have constraints across the board because 
our fiscal levels are not what they used to be, so I cannot 
promise you any specific number until we have fully competed 
and awarded those grants. But our intention is to recruit as 
many patients as we need to carry out a new style of clinical 
trial that we are encouraging; that is, trials that are based 
as much on the genetic damage that has driven the cancer as in 
the organ on which the cancer has arisen. So, there is a new 
style of doing trials that is more costly because it requires 
more preliminary testing.
    And we are also under the direction from a report from the 
Institute of Medicine to pay our investigators a higher fee for 
each patient accrued to those trials, so our trials have become 
more costly. So our interest in expanding our trials, 
especially with all the new therapeutics, not just drugs, but 
also antibodies and immune strategies, and radiotherapy that 
have come our way, is difficult to meet under current 
conditions because we cannot simply do trials. We also have to 
be investing, and this is part of the prioritization question 
in the basic research that fuels new therapeutic approaches.
    And indeed, I would just make a footnote to your question 
about making priority judgments about what we spend our money 
on by pointing to a new initiative at the NCI, despite our 
declining budget, that targets one particular mutant gene 
called RAS that is mutated in over a quarter of all cancers. So 
here is a major target against which, despite knowing about 
this target for 30 years, we have made very little progress.
    So we have started what is called a hub and spoke project 
centered in Senator Mikulski's favorite location, Frederick, 
Maryland, where we have a contract program called the Frederick 
National Laboratory for Cancer Research. We have recruited 
somebody from the University of California at San Francisco to 
come and lead this effort, which involves grantees around the 
country working shoulder to shoulder with a hub of people at 
Frederick who are leading the charge on six specific new 
opportunities for advancing our understanding of cancers that 
are driven by RAS mutations. And this is a way to lead to new 
kinds of compounds that can then be tested nationwide in trials 
that are specifically directed to cancers that have mutations 
in that specific gene.

               CLINICAL AND TRANSLATIONAL SCIENCE AWARDS

    Senator Moran. Doctor, thank you. My time has expired. Dr. 
Austin, I will submit a question in writing to you. I am 
interested in the recommendations by the Institute of Medicine 
in June of 2013 on the Clinical and Translational Science 
Awards, and I am interested in hearing how things are going to 
develop. So I look forward to having a conversation with you. 
Thank you.
    Senator Harkin. Thank you.
    Senator Mikulski.

                  IMPACT OF FUNDING ON U.S. INNOVATION

    Senator Mikulski. Thank you very much, Mr. Chairman. And I 
just want to say to you and to all the Institute directors and 
everyone who works at NIH, we are fortunate to have you. But 
again, I want to come back to your longevity, which shows 
really your dedication, and we view it as a blessing.
    I also want to just comment that we--many of us here are 
worried about the innovation deficit both at NIH and in others. 
There is an effort that is being led by Senator Durbin in this 
area, and to that end, we on the Appropriations Committee are 
going to hold a full committee hearing on innovation to make 
sure that budget cuts and possibilities of future sequester 
does not dampen our standing as a world innovation leader. Yes, 
we worry about the deficit, but we also worry about the 
innovation deficit. So, we are going to be holding that hearing 
on April 29. Dr. Collins will be testifying, the science 
advisor. We are going to be listening to NSF, DARPA, and also 
the Energy Secretary. So we will be doing that.

                             WOMEN'S HEALTH

    In the short time I have because others are now here, I 
want to raise the issue of the Office of Women's Health, that 
which I referenced earlier. It has been flat funded for 3 years 
at $40 million. Now, what I would like to get a picture of is: 
What do you need to have the Office of Women's Health, number 
two, kind of the way we are thinking about running it because 
each and every one of those institutes does important work with 
women. So when we embarked upon our initial endeavor that I 
referenced with Dr. Healy, breast cancer was our preoccupation. 
Those rates are coming down, but lung cancer in women is high.
    Dr. Gibbons could tell me that women with heart disease are 
now escalating, and our symptoms are different, but are early 
diagnoses there? We could go to Dr. Landis and we think about 
something like atrial fib that is there, but if you do not take 
your blood thinner, you could end up with a stroke and 
wondering where are you, et cetera. And then, of course, 
autoimmune is several things, one of which is lupus for which 
only recently the first drug--therapeutic drug in 50 years, of 
course, came out of Human Genome in a Maryland company. So it 
is across all the institutes, which was the idea why we never 
wanted an institute on women; we wanted an office that would 
work. So could you tell us really with the $40 million, how is 
it going, do you need more, and then how do you see this 
working across the institutes?
    Dr. Collins. Thanks for the question. I very much resonate 
with what you are saying, and we have made a lot of progress, 
Senator, thanks to you and others for raising this issue to the 
attention of NIH 20 years ago. We have been fortunate in the 
Office of Research on Women's Health (ORWH) to have remarkable 
leaders in Vivian Pinn, who recently retired, and now Janine 
Clayton, who is a terrific leader for that effort who I just 
met with day before yesterday to go over the status of her 
portfolio. And she has been, as Vivian was, very effective in 
building partnerships across NIH to support special efforts 
that focus on women's health.
    There are particular programs in ORWH, particularly the 
Specialized Centers of Research on Sex Differences, the SCORE 
Programs, as well as training programs that have done a good 
job, I think, in increasing both research on women's health and 
also increasing the proportion of researchers who are women. 
And I would say if you look at the statistics, it looks 
reasonably good, but there are obviously things that we need to 
do better.
    In fiscal year 2013, 57 percent of those enrolled in NIH 
clinical research trials were women--57 percent. And you know 
what that was 20 years ago, in phase III trials, 73 percent. 
So, we have really come a long way. Many of those trials are, 
of course, disease specific and may, therefore, be sex 
specific, for instance in breast cancer. But many of them as in 
heart disease are balanced.
    What we are currently particularly concerned about is 
actually that this same idea has not trickled down in animal 
models, and there is clearly a problem in that many of the 
investigators who are studying models of disease are studying 
only males--male rats, male mice--for reasons that are not 
defensible. And Dr. Clayton and I are about to publish an 
exhortation to the community about this, and we are going to 
start looking very closely at grants to see whether this can be 
corrected because if you did not learn about those sex 
differences in your complete clinical, you are going to miss 
out on an inference that might be really important.
    How much money do we need? Well, we need more money as you 
have heard from all of us in every area of what we are doing. I 
would say Dr. Clayton has been quite effective in brokering the 
dollars that her office has to build relationships and get a 
lot done, but there is a lot more we could be doing.
    Senator Mikulski. Well, as you know, the health data on 
women are changing, and the recent IOM report over the last 2 
years shows that mortality and morbidity among women is on the 
rise. Anyway, a longer topic.
    Dr. Collins. I would love to converse further with you 
about this at any time. It is a passion of mine as well.
    Senator Mikulski. Thank you.
    Senator Harkin. I just want to publicly again thank Senator 
Mikulski. When she first came to the Senate opened our eyes and 
got the NIH to do internal studies to show that women were not 
being included in clinical trials. So it was Senator Mikulski 
who really moved the ball forward on that. That has been over 
20 years ago.
    Senator Mikulski. It has been a long time.
    Senator Harkin. A long time ago. And so, we thank you for 
moving in the right direction.
    Senator Shelby.

                            ANIMAL RESEARCH

    Senator Shelby. Just for the record, I want to touch on 
something Senator Harkin brought up, and that is the research 
on chimpanzees, animals, and so forth. As a kid growing up in 
the Birmingham area in Alabama, I tried to rescue every dog in 
the neighborhood. I still love dogs. I still rescue them. But 
my parents could only feed so many.
    And I was brought to reality, but that did not change my 
caring about animals as all of us do. On the other hand, we are 
all used in research, you know. I have been used by permission 
in research because you gather information that helps 
everything. But is there a real substitute--none of us want to 
be cruel and inhumane to animals. You have used animals in 
biomedical research as you have used us, you know, in different 
aspects. But is there a real substitute for that? Dr. Collins, 
do you want to pick up on that?
    Dr. Collins. I will, and I appreciate your making the point 
that research----
    Senator Shelby. Because we all love--I love dogs still.
    Dr. Collins. So do I.
    Senator Shelby. But I do not collect them anymore, you 
know.
    Dr. Collins. And we have learned enormous amounts from the 
study of animals in research, and we will continue to depend 
heavily on those insights for advances in human medicine, no 
doubt about it. With the chimpanzees, the IOM basically felt 
that there was nothing unique that would justify the continued 
maintenance of hundreds of chimpanzees.
    Senator Shelby. Oh, I totally agree.
    Dr. Collins. We could shrink this back to a small group. 
But your question about a substitution, I am going to ask Dr. 
Austin to say something about an approach to studying toxicity 
of drugs, which traditionally has used animals, and maybe now 
we have got a better way to do this.
    Dr. Austin. Yes, thank you for the question. So this is 
common saw in the translational world that the best animal 
model is the human. And so, what we are trying to do is move 
more of this work to human models, and one of them I actually 
have sitting right in front of me. This is a kidney, but it is 
a kidney on a chip, and it is populated by human kidney cells, 
which is a wonderful model and a much better model of testing 
drugs than in a rat or a chimpanzee and predicting which 
drugs----
    Senator Shelby. Because it is a human being which you are 
working on ultimately to help save, right?
    Dr. Austin. Right. And so, this is part of a tissue chip 
program, that you have probably heard about, that is developing 
so-called organoids. They are three-dimensional micro organs on 
a little micro fluidic platform, a human on a chip. To be able 
to represent human organs in this sort of format that will 
dramatically change, but we believe, both the accuracy and the 
speed with which this testing is done and will make animal 
models irrelevant, obsolete. We are not there yet. We have got 
a lot of work to do. And actually----
    Senator Shelby. But you are going down the right road, are 
you not, Dr. Austin?
    Dr. Austin. Yes.
    Senator Shelby. You are going down the road.
    Dr. Austin. Yes, absolutely.
    Senator Shelby. Well, a lot of my lawyer friends are 
probably glad to hear this because, you know, people have said 
tongue-in-cheek, ``Gosh, if we run out of basic research, we 
could use lawyers as a surplus.'' I said, ``Do not do that.''
    Thank you.
    Dr. Collins. Well, fortunately induced pluripotent stem 
cells came along to save the lawyers because we have this 
amazing new technology, which this committee has heard about, 
but I just got to say it gets better every day. A skin biopsy 
or a blood sample from any one of you could be used to make 
those kidney cells on that chip by doing all of this clever 
manipulation that has only come to light in the last 5 years of 
turning genes on or off. And that means that we could generate 
not just any old kidney chip, but your kidney chip, and find 
out whether that drug that you are going to get is going to be 
good for you or it is going to make your kidneys not so good.

                         BIG DATA TO KNOWLEDGE

    Senator Shelby. Dr. Austin referred to something that I 
just want to pick up on with you, Dr. Collins. The data that is 
collected from all of us in biomedical research willfully and 
knowingly will help to cure diseases and so forth. How 
important is that in the research field, whatever it might be, 
immunization, or neurological, cancer, you name it.
    Dr. Collins. It is critical, and of course we have this 
challenge to both keep track of increasingly enormous 
databases, but also to be sure we are protecting the privacy of 
the individuals' data so that it is not exposed in a way that 
they would not have given consent for.
    I am glad you raised this because NIH has just this year 
initiated a new program we are calling BD2K, Big Data to 
Knowledge. We have enormous opportunities from genomics, from 
imaging, from electronic health records, from everything you 
can think of to make insights about health and disease. Unless 
we focus on the problem of data itself, the sort of new science 
called data science, we are going to get all drowning in the 
data that we have produced instead of making inferences from 
it.
    So we are putting an unprecedented amount of effort into 
it, and this omnibus for fiscal year 2014 has given us a nice 
push in that regard. We aim to ramp that up to $100 million on 
the big data initiatives over the next couple of years, and I 
hired a remarkable scientist from San Diego to lead that 
effort, Dr. Philip Bourne.
    Senator Shelby. Mr. Chairman, one last observation and 
question to Dr. Collins. You mentioned earlier about how 
important it was for scientific investigators to go down the 
right road. Sometimes you do not know you are on the right 
road, and sometimes you are on the wrong road and discover 
something else, though, do you not--that is worthwhile to 
mankind.
    Is that a question of supervision of more investigators, or 
is it a question of better education correlation with what 
people are doing? There may be no answer to it because a lot of 
scientific breakthroughs have come from finding something or 
they did something backwards. Hey, you all know it better than 
I do. Do you want to comment on that?
    Dr. Collins. Absolutely. I think you are quite right that 
many of the most dramatic observations that have led us to 
insights about life and life sciences have come in directions 
that nobody would have predicted were going to be the case, you 
know, from Pasteur on. And serendipity does sort of favor the 
prepared mind. But I worry that at the present time with our 
young scientists feeling so constrained by anxieties about 
support that they may be less inclined when faced with an 
unexpected result to think of that as an opportunity to go down 
a new path because of the necessary kind of need to keep 
pursuing something that they think is in the mainstream and 
more likely to get supported.
    This is one of those secondary effects of a difficult 
budget situation that worries all of us, that creativity, that 
innovation, that risk taking, that sort of seeking a different 
pathway than you had planned to is more difficult. We are 
funding a certain set of grants that aim to try to make that 
possible. The Pioneer Awards are perhaps the best known where 
investigators basically get 5 years of support. And if they 
encounter something they did not expect, they can go after it. 
But many of the other grant systems are not quite so favorable 
for that.
    Senator Shelby. Thank you, Mr. Chairman.
    Senator Harkin. Senator Durbin.

                 NATIONAL INSTITUTES OF HEALTH FUNDING

    Senator Durbin. Thank you very much. Thank you for 
dedicating a major part of your professional life to medical 
research at the premiere biomedical research agency in the 
world. And we are proud of it, and thank you for that. I also 
want to acknowledge--he will have plenty of tributes paid, but 
when the history is written of the NIH, there will be a chapter 
that is entitled ``The Porter-Harkin-Specter'' chapter when 
they made a decision to move forward in a dramatic way and 
double the appropriation for the National Institutes of Health 
over a 10-year period. Tom, of all of your accomplishments, you 
probably created more good for the world with that undertaking, 
although there are lot more that would compete. So I thank you 
for your leadership.
    Dr. Collins, when I met with many of you just a few months 
ago, I sat down and said where do we go next. I am not sure I 
can come with a straight face to Congress and say double it 
again. I am not sure they will do it. And we had a conversation 
about what it takes each year to increase an investment in 
research in NIH and CDC, Department of Defense, healthcare, VA 
health research.
    And you first noted that when we fall behind the cost of 
living, it really ties your hands in the long term to award 
grants. The failure to provide a regular cost of living 
adjustment (COLA) to NIH, as I understand it, has cost you 22 
percent in terms of your ability to award grants for research 
over the last 10 years.
    The President's budget proposed for your agency for the 
next fiscal year gives you, I believe, 0.7 percent COLA. We 
know that the actual cost of living increase will be 1.7 
percent. So built into the President's budget is a further 
decline, falling behind more when it comes to the actual cost 
of living.
    And at that time, I said, ``Give me an idea of what it 
would take in real growth to build this agency forward.'' And 
you said--for the record I am going to ask you to comment on 
this--``Give us 5 percent real growth per year for 10 years 
over the cost of living and we will show you the kind of growth 
in research that America and the world needs.''
    So here you are on the record, and I am going to remind you 
of that conversation since I took it to heart and introduced a 
bill. So please tell me if you still believe that.
    Dr. Collins. Senator, thank you for the question and for 
introducing that bill, and it was a wonderful opportunity to 
talk with you when you came to NIH. And your taking on this 
leadership is deeply appreciated.
    I am showing you here this graph that I think we talked 
about when you came to visit, and, yes, it is exactly as you 
have said.
    [The graphic follows:]

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
    

    Dr. Collins. The blue bars there are the appropriations for 
NIH, but the yellow reflects the effect of the biomedical 
research and development price index (BRDPI). It is sort of 
like a cost of living, but it is our cost of living for doing 
research, the ``BRDPI'' as we call it. And you can see what has 
happened since 2003. At the end of the doubling, those yellow 
bars have been dipping down steadily ever since.
    Earlier when you were at another hearing, I showed another 
version of this graph that basically says if we had stayed on 
the same pathway we were back in sort of 1970 to 1995, which 
was sort of steady growth of inflation plus about 4 percent, we 
would now be at about $40 billion as far as the total NIH 
budget, $10 billion more than what we currently have.
    To get back on that pathway, which would be a wonderful way 
to encourage research to really move forward at the pace that 
it could because we are not limited by talent or by ideas. 
Putting this NIH trajectory on a steady path where you could 
count from year to year on inflation plus a percentage--and 
five would be wonderful--would get us back to where perhaps we 
really need to be in a few years, and would give such a jolt of 
confidence and excitement to frankly a fairly demoralized 
biomedical research community.
    Senator Durbin. And you have told me about it, and we know 
the young investigators are disappearing. Three percent are 
under the age of 36 today. Back 30 years ago it was 19 percent. 
And the other thing that struck me when we talked about AMP was 
you were asking for--asked for and received a commitment of 
$150 million, if I remember correctly, from the top 10 
pharmaceutical companies to be matched by NIH to pursue cures 
and whatever in the areas of Alzheimer's, type 1 diabetes, if I 
am not mistaken, and rheumatoid arthritis.
    To put that in perspective, what I have called for in the 
American Cures Act is $140 billion over a 10-year period of 
time for the four agencies to get real 5-percent growth--$140 
billion. Last year alone we spent over $200 billion in Medicare 
and Medicaid on Alzheimer's--$200 billion. If we could delay 
the onset of that disease, it would more than pay for all of 
the increased investment in research.
    We have got to step back and take stock of what we are 
doing here. As we short change you, we add to the cost of our 
healthcare programs instead of reducing that cost. And just to 
put it in a global perspective, other countries are not 
waiting. Europe is moving forward. The United Kingdom is moving 
forward. In 8 years China will pass us in real dollars spent on 
research. And that ought to be sobering, and I hope it will 
awaken us.
    I know the chairman has a meeting to go in a few minutes as 
I do, too, so I will not dwell on this other than to say I am 
going to keep pursuing this. I really believe that what you are 
doing is really a great credit to this country and will 
alleviate suffering and pain around the world. Thank you, Mr. 
Chairman.
    Dr. Collins. Thank you, Senator.
    Senator Harkin. Thank you, Senator Durbin. Thanks for your 
kind words. I appreciate that.
    Senator Cochran.
    Senator Cochran. Mr. Chairman, I am pleased to join you and 
other members of the committee at this hearing. We appreciate 
your attention to the appropriations request for NIH, and we 
congratulate Dr. Collins and his team for the excellent work 
they continue to do in biomedical research, and the benefits 
that flow from that to our great country.

                        POTENTIAL CARE FOR AIDS

    Last year it came to my attention that at the University of 
Mississippi Medical Center, a pediatrician, Dr. Hannah Gay, 
reported that a patient of hers who is now more than 3 years 
old remained HIV-free after receiving anti-retroviral therapy 
within hours of her birth. We have recently heard about a 
similar case in California. I am impressed with the research 
being done in my State and am hopeful that this could be good 
news for continued research efforts, not only in Jackson, 
Mississippi, but throughout the country.
    What do we know or what do you know about these cases that 
you can share with us in terms of their impact? And what does 
this mean for research and treatment as far as a potential cure 
is concerned?
    Dr. Collins. Well, we have the world's expert in the room, 
Dr. Fauci.
    Dr. Fauci. Thank you, Francis. Thank you for the question, 
Senator Cochran. This is truly a very important case because, 
as you described accurately, this was a mother who came into a 
clinic in Mississippi who was HIV-infected, who had no prenatal 
treatment for her HIV, which put the child at very high risk. 
The astute physicians, pediatricians in Mississippi, instead of 
treating the baby in a prophylactic way to prevent infection, 
they immediately aggressively treated the baby as if the baby 
were infected. After that very rapid application of full-blown 
aggressive therapy as opposed to waiting for a few weeks for 
the diagnosis, the baby turned out actually to be infected.
    By a series of circumstances after several months on 
therapy, there was a discontinuance in care. The mother dropped 
out of the healthcare system, came back several months later, 
and the baby had not been on therapy for several months. The 
physicians watched because they could not find any virus in the 
baby, and now 3 years out the baby is well, growing well, and 
has no evidence of infection, which is likely the first real 
cure of HIV infection.
    That has now triggered an NIH-funded study in which a large 
number of babies who are born of high-risk mothers, namely 
mothers who have not been treated, will be put on aggressive 
therapy to see if, in fact, you can cure babies. Now, the 
reason that is important is that the risk to benefit ratio of 
treating babies aggressively very early on has weighed on the 
side of waiting because you are not sure if you are ever going 
to have the opportunity of curing someone, so you say let us 
not expose the baby to aggressive therapy because you might 
actually hurt the baby if the baby is not infected. And all you 
are doing is going to be saving a few weeks of treatment.
    Now that you know you can actually cure a baby if you are 
aggressive, then the risk benefit ratio switches all the way 
over to the possible benefits. So it was a very important case, 
and it has triggered a study which will begin in the middle or 
end of May, a multicenter study to see if we can verify that 
and apply it to a larger number of babies.
    Senator Cochran. Thank you. That is very exciting, Mr. 
Chairman. And I hope we learn from that that we need to listen 
to these witnesses when they come before our committee. We are 
all going to learn something, and it may be reflected in direct 
appropriations that really do improve not only the lives of 
American citizens, but actually saves their lives. Thank you 
very much.

                               CONCLUSION

    Senator Harkin. Thank you, Senator Cochran. Well, listen, 
thank you all very much again. It is always enlightening. 
Always a pleasure to hear about the National Institutes of Hope 
and what you are doing. I hope that our subcommittee can meet 
the obligations of funding that you have talked about here that 
is in the President's budget, maybe even go beyond that in some 
cases I hope in terms of funding for NIH. We just have to 
recommit ourselves to breaking this logjam of the funding for 
NIH. We have got to get back to the success rate that is less 
than 20 percent across the board. We have got to get down to 
that 15 percent level some time. I think that is what we did 
after we doubled it. It was down around that area, if I am not 
mistaken.
    And so, as I said before, I think the American people 
support that. I do support it. And we just have to meet our 
obligations to do all we can to fund it and, as I said earlier, 
to find any ideas on ways of funding and getting more money for 
NIH. We just cannot give up on this. We just cannot. Too much 
is at stake.
    I often think there are so many young people out there with 
keen minds, want to get into science, biotechnology. We need to 
give them the hope that if they want to pursue that as a life 
career like so many of you have had, that they are going to 
have the opportunity to succeed. They are going to have the 
opportunity to put those keen minds to work and investigating 
and asking those questions of how and why and what happens.
    Basic research to me has always been the most stimulating. 
I often put it in the past in terms of if you have--let us say 
you have 10 doors to a potential cure. Well, if you open one 
door, the odds are, what, 10 to 1, 9 to 1--I am not too good at 
math--that you are not going to find the right door. If you 
open five doors, the odds become even better, or eight or nine. 
That is what basic research is, is opening those doors. A lot 
of times it may not lead to where you think it is going to 
lead, but sometimes that basic research leads to something 
else. I always remember John--Dr. Enders and the kidney cells, 
and the Salk polio vaccine. That is not where he was headed, 
but that is what happened later on.
    And so, to me basic research needs to be--we just have to 
fund it. It always pains me when people say, ``Oh, we put all 
that money into basic research, but, you know, when are we 
going to have an end date? When are we going to find this cure 
and stuff?'' I say, ``Well, that is not a legitimate question 
to ask of basic research. The legitimate question to ask of 
basic research is do you have a question. Does something 
stimulate your curiosity that you are willing to spend some 
time to investigate it and take it as far as you can without 
knowing exactly what the end result is going to be?'' That is 
what basic research is.
    And we need to stimulate that kind of thinking in America, 
that kind of excitement about basic research. And if we do not 
fund NIH, we are telling young people and these keen minds do 
something else maybe. Maybe there is something else for you to 
do. So to me, the funding for NIH is not only the here and the 
now, but it is the next generation, the generation after that 
we encourage to take this up and to devote their lives to 
science and to basic research. We will do whatever we can to 
make sure that that happens.

                     ADDITIONAL COMMITTEE QUESTIONS

    And I thank you all for all of your dedication--your 
lifetime dedication to exploring the frontiers of science and 
health, finding so many cures and therapies. It has been 
amazing, amazing thing to see what has happened in the last 25, 
30 years that I have been here. There next 30 years can be even 
better. Let us make it so. Thank you very much.
    I am supposed to--we will keep the record open--the record 
will remain open until April 9 for Senators to submit other 
questions and for responses to questions.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]
               Questions Submitted by Senator Tom Harkin
                         chimpanzee retirement
    Question. Dr. Collins, I want to thank you for the partnership you 
have had with this subcommittee and the Humane Society on the process 
of retiring chimpanzees from research. As you know, I was one of three 
Senators who requested the Institute of Medicine (IOM) report that 
revealed that chimpanzee research could not be justified except for a 
very few conditions. You are to be commended for adopting the IOM 
recommendations so promptly--the very day the report was released. Your 
decision to retire approximately 310 of the 360 government-owned 
chimpanzees currently in laboratories was suitably bold.
    As a long-time appropriator, however, I know that the work takes 
far longer than the issuing of a policy or the signing of a bill. I am 
keenly aware of the complexity of creating sanctuary space, grouping 
and transporting chimpanzees, and arranging for their care. Many of 
these chimpanzees suffer from illnesses and conditions we gave them for 
the sake of research goals.
    Can you update the subcommittee on the plan for retiring these 
chimpanzees? Can you highlight the challenges and considerations 
involved, including any funding challenges?
    Answer. Thank you for your leadership in working with the National 
Institutes of Health (NIH) and the Institute of Medicine (IOM) to 
resolve issues related to NIH-owned or supported chimpanzees in 
research. An update on the NIH plan for chimpanzee retirement follows. 
Many factors must be considered to ensure a successful chimpanzee 
retirement process: Availability and complexity of creating the 
physical sanctuary space, grouping of animals based on individual and 
group behavioral characteristics, transporting chimpanzees (which 
requires healthy animals and temperate weather), and arranging for the 
care of an aging population. NIH has retired approximately 270 
chimpanzees. At the present time, there is insufficient space in the 
Federal chimpanzee sanctuary system to accommodate all of the 
chimpanzees that will eventually be transferred. Sufficient and 
appropriate sanctuary space is one of the major hurdles to retiring 
more animals. Another is the need to select carefully the 50 most 
suitable research animals prior to retiring the remainder.
    Since 2005, NIH has moved nearly 270 chimpanzees into the Federal 
Sanctuary System. Our plan to transfer all remaining NIH-owned 
chimpanzees from the New Iberia Research Center has been completed. The 
last group of nine chimpanzees was moved to the Federal Sanctuary 
System on June 12th. Currently, Chimp Haven, Inc. is the only facility 
in the Federal Sanctuary System, and it is nearing capacity. As a 
result of natural attrition and careful planning of group composition, 
we anticipate retiring approximately 30 more chimpanzees by the end of 
2014. We are actively looking for alternate sites that meet, or can be 
modified to meet, the high standards required to ensure that these 
chimpanzees are well cared for. These requirements include adherence to 
PHS Policy on Humane Care and Use of Laboratory Animals, the CHIMP Act 
of 2000 (Public Law 106-551); Chimp Haven is Home Act (Public Law 110-
170); the CHIMP Act Amendments of 2013 (Public Law 113-55); and the 
sanctuary specific regulations at 42 CFR Part 9. Chimp Haven, Inc. 
meets these requirements.
    A Request for Information NOT-OD-14-067 (April 7, 2014) was issued 
to solicit information from facilities potentially qualified to join 
the Federal Chimpanzee Sanctuary System. Responses identified three 
potential options for additional sanctuary space, but all would require 
additional and potentially costly construction. NIH is looking at all 
options to develop sufficient sanctuary space but cannot yet estimate 
the time required.
    Second, a major hurdle is the determination of the 50 chimpanzees 
most suitable for critical research. This selection must occur prior to 
retirement because the Chimp Act, as modified by the Chimp Haven is 
Home Act, mandates that retired chimpanzees cannot be returned to 
invasive research. These research chimpanzees will be chosen after an 
extensive NIH review of experimental protocols to ensure that all IOM 
criteria are met. These protocols, and the final selection of research 
animals, may require a period of several years. No chimpanzees will be 
used for NIH-supported invasive biomedical research unless chosen as 
part of the group of 50. Chimpanzees will stay at their current 
facilities, receiving high-quality medical and dental care, in their 
social groups, and under the care of familiar staff. Once the 50 have 
been chosen, remaining animals will be transferred to the Federal 
Sanctuary System as space permits. NIH will regularly reevaluate 
research needs and reduce the number of research animals as warranted.
    Some chimpanzees at the research or reserve facilities will be 
available to move to the Federal Sanctuary System almost immediately 
because they will not be suitable for research protocols. The 
professional staff at each facility is currently identifying these 
animals based on many criteria. We are making progress, but it is not 
yet possible to specify a timeline for the disposition of all 
chimpanzees. It is likely to be several years before the completion of 
all chimpanzee retirements.
                           disease prevention
    Question. I don't have to tell anyone here about my passion for 
disease prevention. NIH has an important role to play in conducting 
research on disease prevention--after all, it is the National 
Institutes of Health, not the National Institutes of Treatment.
    I was very pleased to see that NIH recently released its first 5-
year strategic plan for the Office of Disease Prevention, within the 
Office of the Director. How will this new plan help advance disease 
prevention research? I'm particularly interested in how the plan will 
address gaps in research that are identified by the U.S. Preventive 
Services Task Force.
    As you know, the ACA included a provision that requires insurance 
companies to cover any preventive service recommended by the US 
Preventive Services Task Force (USPSTF) with no deductible, no co-pay. 
When the USPSTF review interventions, they often find that there is not 
enough research to make a recommendation. In those cases, they publish 
a number of questions that need to be answered before a recommendation 
could be made. NIH does not currently use these questions in their 
research agenda planning process.
    The Office of Disease Prevention (ODP) was created in 1986 in 
response to the Health Research Extension Act of 1985 which required 
the creation of an Associate Director for Prevention. ODP includes the 
Office of Dietary Supplements, the Tobacco Regulatory Science Program, 
and supports NIH's Prevention Research Coordinating Committee.
    On January 3, 2014, NIH adopted its first-ever strategic plan for 
disease prevention research, which had the following priorities:
  --Systematically monitor NIH investments in prevention research and 
        assess the progress and results of that research.
  --Identify prevention research areas for investment or expanded 
        effort by the NIH.
  --Promote the use of the best available methods in prevention 
        research and support the development of better methods.
  --Promote collaborative prevention research projects and facilitate 
        coordination of such projects across the NIH and with other 
        public and private entities.
  --Identify and promote the use of evidence-based interventions and 
        promote the conduct of implementation and dissemination 
        research in prevention.
  --Increase the visibility of prevention research at the NIH and 
        across the country.
    Some examples of grants funded by ODP in 2013 are:
  --Transforming Cancer Health Messaging: Engaging Alaska Native People 
        Through Digital Storytelling
  --Cyber Partners: Harnessing Group Dynamics to Boost Motivation to 
        Exercise
  --Uganda Working Group on Non-communicable Disease Risk Factors
  --Psoriasis and the Risk of Diabetes
  --Financial Incentives for Smoking Cessation Among Disadvantaged 
        Pregnant Women
  --Mood and Insulin Resistance in Adolescents at Risk for Diabetes
  --Natural Disaster Effects on Aggressive Children and Their 
        Caregivers
  --Biomarkers in HPA Axis and Inflammatory Pathways for Suicidal 
        Behavior in Youth
  --Collaborating to Measure the Effects of Stroke Preventive 
        Interventions
    Answer. In February 2014, the NIH Office of Disease Prevention 
(ODP) released its first Strategic Plan which outlines the priorities 
that the Office will focus on over the next 5 years. The goal of this 
effort is to increase the scope, quality, dissemination, and impact of 
prevention research supported by NIH. The ODP will achieve this goal by 
providing leadership for the development, coordination, and 
implementation of prevention research in collaboration with NIH 
Institutes and Centers and with other partners. While the priorities 
and objectives outlined in the plan are designed to benefit the broader 
NIH prevention research community, the plan itself was developed as a 
tool for the ODP and does not represent a trans-NIH plan for prevention 
research.
    The ODP strategic plan includes six strategic priorities that will 
allow the Office to expand its influence by, for example, providing 
training in prevention methodology and developing new strategies for 
identifying research needs--activities that may not otherwise be 
addressed by a single NIH Institute or Center but are important for 
advancing disease prevention research more broadly. Interest in disease 
prevention has grown, and NIH has a responsibility to ensure that the 
best prevention science is supported to inform clinical and public 
health initiatives at the individual, organizational, community, and 
policy levels. The strategic priorities included in the plan will allow 
the ODP to play an important role in that process while giving NIH 
Institutes and Centers the flexibility to support prevention research 
within its extramural and intramural programs that best reflects its 
mission and state of the science of their programs.
    Strategic Priority II supports the identification of prevention 
research areas that may benefit from investment or expanded effort by 
NIH. In addition to utilizing results of new portfolio analysis tools 
that are under development (Strategic Priority I), the ODP will achieve 
this goal by working closely with the NIH Institutes and Centers, as 
well as other Federal and non-Federal partners such as the U.S. 
Preventive Services Task Force (USPSTF) to identify and prioritize gaps 
in prevention science and promote research in these areas to broaden 
the knowledge base. The USPSTF conducts scientific evidence reviews of 
a broad range of clinical preventive healthcare services (such as 
screening, counseling, and preventive medications) and develops 
recommendations for primary care clinicians and health systems. As part 
of its clinical recommendation process, the USPSTF identifies 
significant gaps in key areas of knowledge that may limit the full 
realization of the benefits of evidence-based preventive services 
recommendations. Of particular concern to the research community are 
areas that receive an Insufficient or ``I'' recommendation by the 
USPSTF, which indicates that current evidence is insufficient to assess 
the balance of benefits and harms of the service under consideration. 
As the NIH liaison to the USPSTF, the ODP refers Insufficient or ``I'' 
recommendations made by the USPSTF to NIH scientific program staff. The 
NIH Institutes and Centers can use this information to help them make 
decisions during the post peer-review process to further expand 
knowledge within a given research area.
    To further advance Strategic Priority II, the ODP is also 
developing a systematic process that can be used by NIH Institutes and 
Centers to report recent advances or on ongoing research that addresses 
the research gaps identified by the USPSTF and other partners. This 
information, along with identified gaps, will help to highlight 
research areas that are in need of additional support. In addition to 
disseminating this information to our colleagues, the ODP will 
incorporate this information into its own efforts to promote 
collaborative prevention research projects and facilitate coordination 
of such projects across NIH and with other public and private entities 
(Strategic Priority IV).
                        rehabilitation research
    Question. I was pleased to hear that NIH is implementing many of 
the recommendations of the 2012 Blue Ribbon panel on rehabilitation 
research. This is a critical area of research to improve the functions 
and abilities of people with severe injuries, illnesses or conditions 
so that they can live independently.
    This research is done across many Institutes and Centers, but there 
is no consistent definition of rehabilitation research. Without a 
common definition, it is difficult to ensure that core priorities are 
being addressed and to accurately track the science across all of the 
Institutes and Centers. In the fiscal year 2012 Labor-HHS bill, this 
subcommittee asked that NIH adopt an NIH-wide definition. A year later, 
the Blue Ribbon panel went a step further to recommend that NIH adopt 
the WHO definition. What steps is NIH taking to address this issue?
    Rehabilitation research is cross-cutting and focuses on improving 
the ability of people with severe injuries, illnesses, disabilities and 
chronic conditions to improve skills and functions and live as 
independently as possible.
    Medical rehabilitation research is conducted at NIH through 
numerous Institutes and Centers. The research is intended to be 
coordinated by the National Center for Medical Rehabilitation Research 
(NCMRR) within the National Institute for Child Health and Human 
Development (NICHD). One of the main difficulties in coordinating the 
work being done at the various Centers and Institutes is that NIH does 
not have a consistent definition of ``rehabilitation research''.
    The fiscal year 2012 Senate LHHS report language:
      Rehabilitation Research.--The Committee commends NIH for 
        appointing a blue-ribbon panel to evaluate rehabilitation 
        research at the National Center for Medical Rehabilitation 
        Research [NCMRR] and across all of NIH. The Committee requests 
        a copy of the panel's report when it is available. The panel is 
        urged to identify gaps in the field of rehabilitation research 
        and recommend which ICs or other Federal agencies should be 
        responsible for addressing them. In addition, the Committee 
        recognizes the improvements that have been made in delineating 
        rehabilitation research as part of NIH reporting mechanisms 
        established since the passage of the NIH Reform Act. However, 
        the Committee encourages NIH, through the leadership of NCMRR, 
        to further clarify a consistent definition of rehabilitation 
        across all institutes and centers and to seek ways to delineate 
        between physical, cognitive, mental and substance abuse 
        rehabilitation when characterizing NIH-supported research. 
        Finally, the Committee encourages NCMRR to explore the broader 
        social, emotional and behavioral context of rehabilitation, 
        including effective interventions to increase social 
        participation and reintegrate individuals with disabilities 
        into their communities.
    The December 2012 report from the Blue Ribbon Panel on Medicare 
Rehabilitation Research further emphasized the importance of taking 
action to clarify the definition of ``rehabilitation research'' by 
recommending the following:

    ``The study of mechanisms and interventions that prevent, improve, 
restore or replace lost, underdeveloped or deteriorating function, 
where function is defined at the level of impairment, activity and 
participation according to the WHO-ICF model (World Health 
Organization's International Classification of Function, Disability and 
Health).''

    Answer. Since enactment of the 1990 law authorizing the 
establishment of the National Center for Medical Rehabilitation 
Research (NCMRR) under the auspices of the National Institutes of 
Health (NIH), NIH has been using the definition of medical 
rehabilitation research included in the statement of purpose for the 
Center (Sec. 452 of the Public Health Service Act, 42 U.S.C. 285g-4), 
which states that the purpose of the Center is to support research, 
training, and health information dissemination ``with respect to the 
rehabilitation of individuals with physical disabilities resulting from 
diseases or disorders of the neurological, musculoskeletal, 
cardiovascular, pulmonary, or any other physiological system (hereafter 
in this section referred to as ``medical rehabilitation''). This 
definition, which is used consistently across NIH, has allowed medical 
rehabilitation research to be distinguished from other rehabilitation 
research efforts, such as those that involve mental health or addictive 
disorders. The World Health Organization (WHO) definition was adopted 
since that time; while NIH has no objections to using the WHO 
definition, the law would need to be amended to replace current 
language.
    If the definition were changed, it would need to be translated into 
an operational definition to allow appropriate characterization of the 
more than 11,000 competing grants that NIH currently funds each year. 
NIH uses its ``Research, Condition, and Disease Categorization (RCDC)'' 
system--a sophisticated text-data mining software--to categorize and 
cluster words and phrases that reflect agreed-upon definitions. See 
http://report.nih.gov/rcdc/. NIH has already started to develop an RCDC 
``fingerprint'' for medical rehabilitation research, which will allow 
NIH to track the research portfolio as it changes over time, and to 
understand the breadth and depth of the portfolio as part of the 
upcoming effort to develop a strategic research plan.
                        medication in pregnancy
    Question. Each year more than four million women give birth in the 
United States and more than 3 million breastfeed their infants. Nearly 
all of these women will take a medication regularly or receive a 
vaccine, but little is known about the effect of most drugs on the 
woman or her child. For most drugs, we don't know the impact on child 
development and we don't know the impact on the effect of the 
medication. A study in the American Journal of Medicine illustrated 
that fewer than 10 percent of medications approved by the FDA since 
1980 have enough information to determine their risk for birth defects. 
Women and doctors are forced to guess whether to continue their 
treatment.
    This gap in understanding has become increasingly problematic as 
more women delay childbearing and rates of chronic disease rise. More 
expectant mothers than ever before are requiring medications to manage 
conditions such as diabetes, hypertension, depression, and asthma.
    What types of research activities is NIH engaged in to fill these 
research gaps? What is the state of our understanding of the effect of 
drugs during pregnancy and breastfeeding?
    Answer. Primarily through its Obstetric and Pediatric Pharmacology 
and Therapeutics Branch (OPPTB), the Eunice Kennedy Shriver National 
Institute of Child Health and Human Development takes a range of 
approaches to support research activities on medication use in 
pregnancy and during breastfeeding, collaborating with other NIH 
Institutes and Centers as appropriate for their areas of expertise.
    The Obstetric-fetal Pharmacology Research Units (OPRU) Network was 
established in 2004 with four academic research institutions to improve 
the safety and effectiveness of the medications commonly used (but 
often never having been tested) in women during pregnancy and 
postpartum. The OPRU Network has provided critical research 
infrastructure for a multidisciplinary collaboration of researchers to 
perform basic/translational studies and phase I/II clinical trials 
aimed at characterizing and evaluating the impact of medications on 
metabolism and physiological, cellular, and molecular changes during 
pregnancy. The OPRU Network also conducted opportunistic studies of 
medications in women who were already taking these medications during 
pregnancy. More than 100 research articles from these studies have been 
published in peer-reviewed scientific journals.
    Some study results have directly informed clinical practice. For 
example, a study of the anti-diabetes drug glyburide use during 
pregnancy showed that glyburide can cross the placenta and that the 
drug's concentrations are about 50 percent lower in pregnant women with 
type 2 diabetes than in non-pregnant women with type 2 diabetes, 
suggesting that a higher dose may be needed to achieve optimal 
therapeutic effects. A study of oseltamivir, a medication for treating 
and preventing influenza, indicated that the drug plasma concentrations 
are much lower and apparent clearance significantly higher in pregnant 
women compared with non-pregnant women, suggesting an increased dose 
may be necessary to achieve comparable effects.
    The OPRU Network currently supports a randomized clinical trial to 
determine the pharmacologic effects of anti-diabetic drugs (glyburide 
and metformin) separately, and in combination for management of 
gestational diabetes, a phase I clinical trial to evaluate the effect 
of early treatment with pravastatin for prevention of preeclampsia, and 
an exploratory study to identify vaginal biomarkers of response to 
progestin treatment of preterm birth. The Network also is funding 
several investigator-initiated grants on nicotine replacement therapy 
for smoking cessation during pregnancy and safety and effectiveness 
studies on anti-hypertensive medications in pregnancy. In addition, to 
encourage young investigators working in this area of research, the 
OPPTB supports several postdoctoral training programs.
                          cancer and distress
    Question. I know first-hand that a cancer diagnosis can be 
devastating for patients and families. Studies show that half of all 
cancer patients experience psychological and social distress as a 
result of their cancer diagnosis. But there is good news: a study 
conducted by Dr. Barbara Andersen and published in the Journal of 
Oncology showed that patients with breast cancer who receive distress 
screening and social and emotional follow-up care have a 45 percent 
reduced risk of cancer recurrence, a 56 percent reduced risk of death; 
and a 59 percent reduction in breast cancer death even WITH recurrence.
    These are remarkable outcomes. Yet the Institute of Medicine has 
consistently concluded that cancer care provides state of the art 
biomedical treatment but does little address the psychological and 
social needs of cancer patients.
    What requirements, if any, does NCI have on its intramural and 
extramural research programs to screen patients for distress and ensure 
follow up care? What kind of research is being done, either at NCI or 
at the Mental Health Institute, to further this promising area of 
research?
    Answer. As the Federal agency that supports the Nation's cancer 
research enterprise, the National Cancer Institute (NCI) conducts and 
facilitates research and the development of valid tools that can inform 
standard clinical practice and medical decisionmaking. However, NCI 
does not establish standards of care or place requirements on care-
givers. Other Federal agencies and private-sector organizations (such 
as specialty societies and cancer-specific groups) develop medical 
recommendations for cancer, building upon NCI's research and the work 
of these other agencies in the Department of Health and Human Services 
(HHS) to develop guidelines or recommendations about all aspects of 
medical practice related to cancer care.
    Still, it is important to emphasize that both NCI and the National 
Institute of Mental Health (NIMH) support research related to screening 
for emotional distress experienced by patients who receive a cancer 
diagnosis and subsequent treatment. In this area, NCI's role is to fund 
and support research that shows the efficacy and impact of systematic 
screening for emotional distress on cancer survivors' subsequent health 
and function. Historically, we have funded--and we continue to 
support--randomized controlled trials that test the ability of 
psychosocial and behavioral interventions to reduce psychological 
distress and promote adaptation to illness. This research has shown 
that a wide variety of interventions (both at the individual and group 
levels and varying in content) are effective in improving understanding 
of illness and adherence to treatment, reducing depression, fatigue, 
and stress, and adopting healthy behaviors.
    A key response by NCI to the Institute of Medicine (IOM) report, 
Cancer Care for the Whole Patient: Meeting Psychosocial Health Needs, 
was to include attention to survivorship and palliative care in the 
funding of NCI's Community Cancer Centers pilot program (NCCCP). One of 
the deliverables for funded NCCCP sites was to develop the capacity to 
screen for distress and refer individuals to appropriate psychosocial 
care as needed. NCCCP sites also had to expand their psychosocial 
programs, as well as training of staff to identify and manage these 
issues in patients being treated at each institution. In addition, NCI 
solicited information from the clinical-investigator community about 
the tools they are using to screen for distress, as part of the Grid 
Enabled Measures (or GEM) initiative. The GEM database collects 
questions that measure unmet needs, depression, and anxiety. These are 
available for clinicians and researchers to access, evaluate, and (with 
the exception of copyrighted instruments) be used to care for patients 
under active treatment and other cancer survivors. NCI is initiating 
collaborations with the American Society of Clinical Oncology (ASCO) 
and the Commission on Cancer. In 2012, the Commission gave member sites 
until 2015 to implement psychosocial distress screening in their 
centers.
    NIMH has funded several studies in recent years investigating 
psychological distress and depression associated with cancer diagnosis 
and treatment. For example, NIMH has supported the development of the 
Mental Health Assessment and Dynamic Referral for Oncology software, 
which enables oncology treatment providers to screen for and monitor 
several patient care domains, including: (1) mental health functioning; 
(2) cancer-related symptoms and side effects; (3) the patient-provider 
partnership; (4) barriers to treatment; and (5) adherence with medical 
regimen and lifestyle change recommendations. Another team of NIMH-
funded researchers has studied whether depression can be prevented in 
patients with head and neck cancer during treatment (with relevance to 
other cancers), as well as whether initiating prophylactic 
antidepressant treatment can improve timely completion of the cancer 
therapy and preserve quality of life. Other NIMH-funded researchers 
have studied the impact of cancer treatment, as opposed to diagnosis, 
on mental health--for example, whether antidepressants can prevent the 
impact of melanoma treatment on the brain, endocrine, and immune 
systems.
    In addition to these extramural efforts, the NIMH Division of 
Intramural Research Programs conducted a multiyear study investigating 
biological, psychological, and social factors that affect living with a 
chronic life-threatening illness such as cancer, HIV, or other rare 
diseases, as well as suicide risk and palliative care decisionmaking 
procedures for treating children and adolescents with life-threatening 
conditions.
                                 ______
                                 
            Questions Submitted by Senator Richard J. Durbin
                           american cures act
    Question. In 1965, the U.S. spent more than 25 percent of our non-
defense discretionary budget on research and development--last year 
that number was 10 percent. Between 2003 and 2012, the NIH budget has 
not even kept up with inflation, resulting instead in a 22 percent 
decline in real purchasing power. The number of research grants at NIH 
has declined every year for the past 10 years.
    Dr. Collins, you have warned that continuing this trend of funding 
will cause some of America's best young researchers to take their 
talents to other industries--or other countries.
    What promising breakthroughs or developments do you think are at 
risk of delay due to the U.S. Federal Government failing to keep pace 
with inflation in funding the NIH?
    Answer. NIH-supported researchers make scientific discoveries every 
day, advancing research related to countless health and disease issues. 
While it is impossible to predict exactly when breakthroughs will occur 
in a particular scientific field, the pace of discovery will be delayed 
if funding fails to keep pace with inflation. For example, this could 
cause delays in the significant progress that researchers are making in 
developing a universal flu vaccine that could offer protection against 
any flu virus strain, including those that may cause pandemics. 
Similarly, NIH efforts to develop a vaccine for HIV or even a cure for 
AIDS may be hampered.
    In cancer research, recent results indicate that immunotherapy may 
be a new and effective form of treatment. However, opportunities to 
expand this research to include additional patients and other types of 
cancer may not be possible if NIH funding remains stagnant. NIH also is 
engaged in extensive efforts to respond to the emerging public health 
threat from antimicrobial resistance (AMR), including support for basic 
research, development of new and faster diagnostics, and creating a 
national database of genomic sequence data. These efforts could be 
hampered if NIH funding does not keep pace with inflation. NIH efforts 
to leverage its resources in partnerships with the private sector also 
could be disrupted, such as the new Accelerating Medicines Partnership 
(AMP) that brings biopharmaceutical companies and several nonprofit 
organizations together with NIH to identify and validate biological 
targets of disease for future drug development.
    Please describe the biomedical discoveries, training of junior 
scientists, and economic benefits that could result if NIH was provided 
with a steady source of funding that increased year after year to keep 
up with inflation?
    Answer. A steady source of funding helps support biomedical 
scientists. Having a budget that keeps pace with inflation would help 
to reassure scientists that they will have the necessary support for 
the duration of their projects. Steady investment in the National 
Institutes of Health (NIH) helps enable our researchers to achieve 
their full scientific potential in all research areas, fueling 
biomedical discoveries from autism to Alzheimer's disease to cancer to 
diabetes. Inflation-adjusted budgets also may enable NIH to award more 
grants to fund investigator-initiated research, thereby allowing the 
country's most innovative scientific thinkers to chart the best path 
forward in their research areas.
    Promising young scientists who have chosen career paths outside of 
biomedical research in recent years due to uncertain funding also would 
be encouraged by a stable funding model and may reconsider pursuing 
research careers. Coupled with NIH's commitment to fund new 
investigators at success rates equal to those of established 
investigators, this scenario would enable NIH to attract and sustain a 
talented biomedical research workforce.
    NIH investments reap substantial economic benefits; the agency 
directly supports about 300,000 researchers at more than 2,500 
institutions in every state, and these investments spur additional job 
creation in those communities as well. In 2012, United for Medical 
Research estimated that NIH investments supported more than 402,000 
jobs and resulted in $57.8 billion in economic output nationwide. A 
report from the Milken Institute indicates that a $1 increase in NIH 
funding can increase the bioscience industry output by $1.70 in a given 
year, and the long-term effects could be even greater. Given these 
short-term economic effects, an inflation-adjusted budget for NIH could 
spur job growth across the country, increase economic output, and 
reduce health spending by producing better, more cost-effective 
treatments and prevention strategies. Over the long term, increased 
support for NIH will lead to reductions in disease, longer lifespans, 
and improved quality of life for all Americans.
                 sequestration and government shutdown
    Question. The National Institutes of Health is the Nation's medical 
research agency and the leading supporter of biomedical research in the 
world. More than 80 percent of the NIH's budget goes to over 300,000 
research personnel at more than 2,500 universities and research 
institutions through the United States. Last year, sequestration cut 
the NIH's $30.7 billion budget by almost $1.6 billion. The deleterious 
effects of sequestration were compounded by the government shutdown 
which took place October 1 to October 16 of 2013 and temporarily 
curtailed most of NIH's operations.
    Please summarize the impact that sequestration and the government 
shutdown had on NIH's ability to award grants and support the training 
and education of scientists. Please describe the impact that 
sequestration and the government shutdown had on biomedical innovation 
and how the cuts in funding impacted patients currently enrolled in 
clinical trials.
Impact of Sequestration
    Answer. Sequestration dampened NIH's ability to support biomedical 
research. The overall award rate for NIH research project grant 
applications in fiscal year 2013 fell to approximately 15 percent, a 
historic low.\1\ \2\ Compared to fiscal year 2012, in fiscal year 2013, 
NIH funded approximately 750 fewer competitive research project grants 
(e.g., new or renewal applications) that were determined to be highly 
meritorious in grant review, including over 200 fewer competing renewal 
applications. Competing renewal applications represent promising 
follow-on research stemming from previously funded grants. Lack of 
continued funding diminishes the NIH's ability to leverage previous 
investments and capitalize on recent scientific progress.
---------------------------------------------------------------------------
    \1\ http://nexus.od.nih.gov/all/2014/03/05/comparing-success-award-
funding-rates/#sthash.aM0tN2GL.dpuf
    \2\ NIH's definition of ``award rate'' is the number of awards made 
in a fiscal year divided by the absolute number of applications.
---------------------------------------------------------------------------
    NIH Institutes and Centers (ICs) were also forced to reduce funding 
for noncompeting, ongoing research grants. Reductions varied by IC, but 
the NIH-wide average was -4.7 percent. Further, at least ten new 
funding initiatives (``request for applications'' or ``request for 
proposals'' concepts) were planned but not published, including cancer 
studies that could have improved our ability to distinguish accurately 
non-lethal tumors from life-threatening ones, and autism studies to 
investigate genetic and environmental factors that affect the risk of 
autism in preterm infants.
    Many of the NIH ICs also reduced their funding for training grants 
and fellowships. For example NIGMS, which sponsors the majority of NIH-
supported pre-doctoral trainees, funded 186 fewer trainees than it 
would have without sequestration. Trainees who were already funded also 
were affected, as there was no increase in stipend levels for National 
Research Service Award recipients in fiscal year 2013.
    Sequestration also diminished NIH's ability to conduct research at 
the Clinical Center. Approximately 750 fewer new patients were admitted 
to the NIH Clinical Center, a decrease from 10,695 new patients in 2012 
to approximately 9,945 new patients in 2013. This reduced the number of 
patients who could have benefitted from enrollment in clinical 
protocols, as well as slowed the pace of important clinical research. 
Note that while much of the decrease in enrollment numbers is due to 
funding, patient recruitment is dependent on multiple factors.
    Funding cuts driven by sequestration have had ripple effects 
throughout the biomedical research community. One recent survey 
examined sequestration's impact on research conducted by universities 
across the country.\3\ The most commonly cited impacts of the sequester 
among survey respondents were a reduction in the number of new Federal 
research grants (70 percent of responding universities), delayed 
research projects (also 70 percent), personnel reductions (58 percent), 
reduced research activity (81 percent), admission of fewer graduate 
students (23 percent), as well as tuition reductions and reduced 
stipend levels for students (14 percent).
---------------------------------------------------------------------------
    \3\ Association of American Universities, Association of Public and 
Land-grant Universities, and The Science Coalition. Survey on 
Sequestration Effects: Selected Results from Private and Public 
Research Universities. November 2013.
---------------------------------------------------------------------------
Impact of Government Shutdown
    The Government shutdown impacted NIH and the biomedical research 
community. Approximately 75 percent of the NIH workforce was furloughed 
during shutdown. For the community of NIH's extramural investigators, 
shutdown caused delays in grant review and funding processes. 
Typically, NIH receives the largest number of grant applications in 
October. Because of the prolonged shutdown, all of the October receipt 
dates were rescheduled for November, including those for NIH's largest 
grant activities, such as the investigator initiated R01 applications, 
Small Grants (R03), Exploratory Development Grants (R21), AREA awards 
(R15), and Career Development (K) activities. Reviews of more than 
11,000 grant applications were delayed by the shutdown.
    October is also one of the 3 months with the largest volume of NIH 
Scientific Review Group meetings, the first step of peer review. Over 
200 Scientific Review Group meetings had to be rescheduled due to the 
shutdown; most of the October meetings involved reviewers travelling to 
meetings scheduled to be convened ``in-person''. These ``in-person'' 
meetings had to be rescheduled, and travel arrangements had to be 
cancelled and re-arranged.
    The NIH Intramural Research Program (IRP) was also profoundly 
affected and lost progress during the shutdown. The Clinical Center did 
not enroll any new patients in clinical trials or to start new trials. 
Therefore, approximately 200 new patients were not admitted to the 
Clinical Center. Of those denied access, 30 were children, including 10 
with cancer. Only 15 to 20 percent of IRP staff were ``excepted'' from 
furlough, so that they could protect life (mostly in the Clinical 
Center, where 75 percent of the staff were required to work), guarantee 
safety (infrastructure support including security and the power plant), 
and protect large investments in materials and property (animals, cell 
cultures, and expensive equipment).
    The shutdown took a toll on NIH intramural training programs and 
trainees, too. In addition to being a biomedical research enterprise, 
NIH is the largest training facility in the world for biomedical 
researchers. During the shutdown, there were approximately 4,000 
postdoctoral fellows, 800 post baccalaureate students, 500 graduate 
students, and 45 medical students who were unable to conduct their 
research. For many of these trainees, time is of the essence. Their 
appointments are time-limited (less than 1 year for the medical 
students, up to 2 years for the post baccalaureate students, and 
usually three to 4 years for the postdoctoral fellows and graduate 
students). Loss of a few weeks of research and mentoring as well as the 
additional work time needed to regain momentum--while cell lines are 
started up again, animals are bred, and experiments that may have 
suffered in the shutdown are repeated--represent a significant 
proportion of their NIH training experience that could affect their 
future careers.
                        congenital heart disease
    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 people with congenital heart defects are living into adulthood.
    The healthcare reform law includes a provision 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 2014 
provided the CDC with $2.9 million in new funding for enhanced CHD 
surveillance. 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 NIH systematically responding to this new population of 
survivors reaching adolescence, adulthood, and advanced age?
    How is NIH utilizing adult congenital heart disease research 
experts in these efforts?
    How is NIH supporting adult CHD professionals so the field can 
grow? 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. Advances in diagnosis and care have led to significant 
improvement in survival rates for Congenital Heart Disease (CHD) such 
that more adults than children are now living with CHD. The National 
Heart, Lung and Blood Institute (NHLBI) supports research on the causes 
of CHD and the evolving natural history and co-morbidities in adults 
with CHD across the lifespan. For example, the Bench to Bassinet 
Program (B2B) is identifying genetic and epigenetic causes of CHD to 
help risk-stratify and personalize treatment for children and adults 
with CHD. The Pediatric Heart Network (PHN) was launched in 2001 to 
conduct studies to improve outcomes and quality of life in children 
with heart disease and includes experts in adult congenital heart 
disease (ACHD). The PHN is following the largest assembled cohort of 
individuals with single ventricle physiology into adulthood to 
determine barriers to transitioning to adult care and to evaluate their 
health status and co-morbid conditions at specific intervals. The PHN 
is also in the process of launching a trial in adolescents and young 
adults with single ventricle physiology to assess whether use of a 
phosphodiesterase-5-inhibitor medication will prevent functional 
deterioration and delay the onset of heart failure.
    NHLBI also partners with ACHD-themed organizations to advance the 
field of ACHD research, such as The Health, Education and Access 
Research Trial (HEART-ACHD) and The Research Empowerment for Adult 
Congenital Hearts (REACH) project, both funded by NHLBI and conducted 
in partnership with the Adult Congenital Heart Association (ACHA) and 
the Alliance of Adult Research in Congenital Cardiology (AARCC). In 
June 2014, NHLBI and the ACHA will host a working group, ``Adult 
Congenital Heart Disease: Emerging Research Questions,'' to identify 
critical research gaps in the care of adults with CHD. This group will 
build partnerships between ACHD experts and experts in the 
complementary fields of adult cardiovascular care and pediatric 
cardiology. Participants will develop methodological approaches that 
leverage recent progress in multicenter ACHD research and existing 
congenital heart disease data infrastructure, and will develop 
strategies to engage patients in the development and execution of 
research studies.
    To ensure a robust community of ACHD investigators spanning basic 
and clinical research, NHLBI supports institutional training grants for 
CHD, the PHN Scholars award, to fund small pilot studies, and 
individual career development awards for ACHD investigators For 
example, an NHLBI-supported career development awardee is developing, 
testing, and validating a Quality Assessment Tool for Adults with 
Congenital Heart Disease (QAT-ACHD) for the outpatient management of 
selected ACHD conditions to help standardize high-quality ACHD care. 
Another NHLBI career development awardee is studying the role of 
myocardial fibrosis in three ACHD conditions. The same investigator has 
also secured funding from the Eunice Kennedy Shriver National Institute 
of Child Health and Human Development (NICHD) for a pilot study on 
enlarged thoracic aortas in patients with bicuspid aortic valve. 
Mechanisms such as these are designed to ensure growing expertise in 
the field of ACHD research, with a strong focus on the long-term 
implications of CHD and its treatment for the increasing number of 
persons who survive for many decades after diagnosis.
                                 ______
                                 
             Questions Submitted by Senator Jeanne Shaheen
                                 oppnet
    Question. Can you provide an update about OppNet, the 5-year 
initiative to support basic behavioral and social sciences research 
that began in 2010? What can you tell us about the findings of that 
initiative? When will a report be available?
    Answer. Between October 2010 and May 2014, the Basic Behavioral and 
Social Science Opportunity Network (OppNet) provided $64.2 million to 
fund 152 extramural research projects. OppNet lists all its grants by 
original year of funding at http://oppnet.nih.gov/resources-
initiatives.asp. Among the OppNet grants is early investigator Dr. 
Santosh Kumar's Predicting Smoking Abstinence via Mobile Monitoring of 
Stress and Social Context. This study demonstrates that modern sensor 
technology can obtain a much more detailed and accurate representation 
of personal and environmental influences on smoking than previously 
possible. Based partially on this work, Popular Science magazine named 
Dr. Kumar one of the 10 most brilliant young scientists. Another 
project, Neural Mechanisms of Habit Formation and Maintenance, analyzes 
cellular, molecular, and circuit mechanisms to understand how behaviors 
become ``automatic'' regardless of outside influences. Dr. Henry Yin 
found that stimulating mouse neurons to generate dopamine can foster 
the adoption of healthy behaviors and reduce unhealthy behaviors--all 
without providing incentives (e.g., food rewards). These findings, 
already appearing in at least five peer-reviewed publications, suggest 
exciting possibilities for future studies with important clinical 
implications.
    OppNet has expanded both the perspective of researchers and NIH 
program directors. Nineteen of OppNet's 28 new investigators (68 
percent) received non-Federal funding prior to applying, compared with 
21 percent of basic behavioral and social sciences research (basic-
BSSR) and 39 percent of applied behavioral and social sciences research 
(applied-BSSR)--an example of the initiative's success at expanding 
NIH's scope of basic-BSSR. NIH program directors report that OppNet has 
increased their knowledge of other NIH Institutes and Centers (ICs)' 
missions and research interests and that OppNet has allowed them to 
solicit and fund projects that likely could not have occurred without 
OppNet's infrastructure. Perhaps the best examples to date are the 
grants funded through the funding opportunity, Basic Behavioral 
Research on Multisensory Processing http://oppnet.nih.gov/resources-
2013fundedapp.asp. These projects explain how a combination of visual, 
auditory, olfactory, gustatory, non-pain somatosensory, and/or 
vestibular input influences basic perceptual and behavioral processes. 
This initiative stimulated new collaborations between ICs that were 
supporting research on sensory processing, but from the perspective of 
single sensory systems, such as vision or audition.
    ICs are organized somatically or by disease. OppNet's 
infrastructure facilitates the trans-sensory and transdisciplinary 
research projects that likely would lack a clear ``home.'' Moreover, 
OppNet has been so successful at coordinating basic and applied BSSR 
across the NIH that some ICs decided to fund all or part of 23 
additional projects beyond what was planned for in the OppNet budget. 
As the grants funded under OppNet have not gone through a full five-
year funding cycle, a formal and comprehensive program evaluation would 
be premature at this time. However, OppNet makes its activities and 
accomplishments available to the public through its Web site at http://
oppnet.nih.gov/.
                                diabetes
    Question. I understand that, as a result of previous studies, there 
is evidence of a link between poor blood glucose control and 
development of diabetes complications, and the tremendous long-term 
benefits of early, effective blood glucose control, particularly in 
recent onset diabetes. Can you tell me what the agency is doing to 
better understand the underpinnings of complications like kidney 
disease?
    Answer. Controlling and preventing diabetes are the best approaches 
to preventing or minimizing its many health complications, including 
kidney disease. Diabetes--both type 1 and type 2--is the major cause of 
end-stage kidney failure. The landmark NIH-supported Diabetes Control 
and Complications Trial (DCCT) and its follow-up study, the 
Epidemiology of Diabetes Interventions and Complications (EDIC), 
demonstrated how critically important it is to control blood glucose 
levels early in the course of type 1 diabetes in order to reduce the 
likelihood of subsequent complications. DCCT participants who 
intensively controlled their blood glucose levels had significantly 
lower rates of eye, nerve, kidney, and cardiovascular complications 
than those who received standard care. This effect extended for many 
years after the study ended.
    A second landmark NIH-supported clinical trial, the Diabetes 
Prevention Program (DPP), showed that an intensive lifestyle 
intervention designed to achieve modest weight loss through a 
combination of diet and exercise lowered type 2 diabetes rates by 58 
percent, and that the generic diabetes medication metformin reduced 
diabetes rates by 31 percent, relative to placebo. A follow-up study to 
the DPP, the DPP Outcomes Study (DPPOS), is assessing the long-term 
effects of interventions used in the DPP on the development of type 2 
diabetes and its complications. After 10 years of follow-up, DPPOS 
found that the lifestyle intervention continued to dramatically reduce 
the development of type 2 diabetes--and consequently its 
complications--and also reduced cardiovascular risk factors.
    Diabetes is the leading cause of kidney disease, followed by high 
blood pressure. Abnormally high blood glucose levels damage the 
kidney's filtering units, which progressively and irreversibly impairs 
kidney function. Thanks to NIH-supported research, scientists have made 
great progress in developing methods, in addition to controlling blood 
glucose levels, which slow the onset and progression of kidney disease 
in people with diabetes. Two types of drugs used to lower blood 
pressure, angiotensin-converting enzyme (ACE) inhibitors and 
angiotensin receptor blockers (ARBs), have proven effective in slowing 
the progression of kidney disease in people with diabetes or high blood 
pressure.
    Because there is no way, at present, to restore kidney function 
once it is lost, NIH research focuses on early detection of kidney 
disease and strategies to slow or prevent the progression of disease. 
The Chronic Renal Insufficiency Cohort (CRIC) Study, one of the largest 
and longest ongoing studies of chronic kidney disease epidemiology in 
the United States, is examining the natural history of kidney disease 
as well as the broad range of illnesses experienced by people with 
kidney disease. NIH is supporting a study that aims to identify 
biomarkers that indicate a risk of progression of kidney disease. 
Research supported by NIH has enhanced our understanding of the origin 
of scar tissue that is common in many forms of kidney disease, how it 
can impair kidney function, and how it might be prevented or treated. A 
new initiative, currently in development, will address challenges 
associated with growing nephrons, the kidneys' basic filtering unit. 
NIH supports several studies that the private sector most likely would 
not undertake, including pilot studies of novel therapies for kidney 
disease.
                             emergency care
    Question. The NIH recently created a new division, the Office of 
Emergency Care Research. Considering that in New Hampshire, and 
throughout the United States, there is an epidemic of narcotic 
prescription abuse and overdose deaths, what can the this new office do 
to help emergency providers curtail excess narcotic prescribing? How 
can we increase awareness among providers to decrease medically 
unnecessary narcotic prescriptions?
    Answer. The Office of Emergency Care Research (OECR) was 
established in 2012 to coordinate and develop emergency care research 
across the National Institutes of Health. Emergency departments (EDs) 
are unique treatment settings in that they serve some patient 
populations that have little or no access to medical care, and who have 
few available resources. For example, EDs may be the only facilities at 
which poor and underserved populations receive care. For substance-
using populations, they provide a unique opportunity to assess the 
overall health needs of the patient and link them to the care and the 
support required to meet all of their health needs. OECR and the 
National Institute on Drug Abuse (NIDA) are concerned about the 
epidemic of narcotic abuse and are aware of the role of the emergency 
care system in reducing this abuse.
    NIDA is investing in research to develop clinical interventions 
tailored to the ED setting. The goals of these interventions are to 
facilitate accurate diagnoses and linkage to long-term care programs to 
protect the overall health of the individual. Halting accidental or 
unnecessary opioid prescriptions is a key component to thwarting the 
devastating rise in opioid overdoses. For this reason, NIDA is 
supporting research that will increase ED physician knowledge when 
treating opioid patients by:
  --identifying ways to effectively implement the use of prescription 
        drug monitoring programs (PDMPs) within the ED to decrease 
        prescription opioid prescribing, overdoses, and deaths. 
        Widespread use of PDMPs will provide ED physicians with the 
        information they need to prescribe opioids to those patients 
        who would benefit most from these essential medications, while 
        preventing these medications from reaching populations for 
        which they are not intended. (For more details see NIH grant 
        1R01DA036522-01.)
  --developing improved, non-invasive devices that can detect traces of 
        narcotics and alcohol. This will help ED physicians to diagnose 
        and treat patients with substance abuse issues, because an 
        accurate diagnosis of substance abuse is the first step to its 
        treatment. (For more details see NIH grant 5R44DA031530-03.)
    Since assuming the position of Director of OECR, Dr. Jeremy Brown 
has met with program officers and senior staff at NIDA to discuss 
strategies to increase research on drug abuse in the emergency care 
setting. In addition, in October 2013, OECR, CDC, and NIDA staff were 
scheduled to attend a special day training session on effective 
approaches to addressing substance abuse disorders in the Emergency 
Department. This conference was held as part of the annual meeting of 
the American College of Emergency Physicians. Although the Government 
shutdown prevented NIH staff from attending in person, this meeting 
emphasizes the way in which NIDA, OECR and professional organizations 
are cooperating to address the substance abuse epidemic.
    Funding for research on the narcotic epidemic is provided by NIDA, 
and the Office of Emergency Care Research will continue to work with 
staff from NIDA to support and grow initiatives in this area.
                                 asthma
    Question. In November Congresswoman DeLauro and I wrote to 
Secretary Sebelius to inquire about a provision in the National Heart, 
Lung, and Blood Institute's (NHLBI) 2007 Expert Panel Guidelines for 
the Diagnosis and Management of Asthma that recommends that physicians 
who treat the majority of children with asthma ``determine exposures, 
history of symptoms in presence of exposures, and sensitivities.'' They 
make this recommendation so that ``physicians can advise patients on 
ways to reduce exposure to allergens.'' While it has been many years 
since release of the guidelines, we are concerned that we are failing 
to meet this objective. I'd like your assurance that this work will 
remain a high priority for the NIH and that you will continue to work 
with all stakeholders to accelerate implementation of this laudable 
objective.
    Answer. NHLBI's National Asthma Education and Prevention Program's 
(NAEPP) Guidelines Implementation Panel Report offers suggested 
strategies to enhance dissemination and adoption of key recommendations 
in the Guidelines. These strategies were offered as a list of possible 
activities for NAEPP member organizations and other professional, 
private sector, state and local government, and patient groups to 
consider undertaking within their respective organizations in order to 
improve asthma care, which many organizations have done. All programs 
address exposures to environmental allergens and irritants as part of 
the comprehensive approach to asthma necessary to achieve and maintain 
asthma control.
    National professional societies and patient groups and local 
healthcare and community groups have made considerable progress in 
engaging primary care providers, allergists, and representatives of 
health plans to identify and overcome local barriers and accelerate 
implementation of recommendations in the Guidelines, including those 
relating to control of allergens. For example, the Centers for Medicare 
and Medicaid Services Health Care Innovation Awards Program included 
five awardees that address asthma; all of these programs incorporate 
attention to environmental allergens. The Environmental Protection 
Agency's (EPA) vibrant Community Network (http://
www.asthmacommunitynetwork.org/) and annual EPA leadership Awards 
program offer outstanding examples of community organizations, 
clinicians, and healthcare administrators, including Medicaid service 
providers, across the country working together on programs that 
incorporate measures to control environmental asthma triggers, 
including allergens, into comprehensive asthma management. The Centers 
for Disease Control and Prevention's National Asthma Program and the 
NHLBI's National Asthma Control Initiative showcase tools and programs 
developed by state public health and local community clinics that can 
be adapted by other stakeholders. These tools include home-visit 
guides, environmental assessment checklists, and clinical pathways for 
assessing, treating, and monitoring all aspects of asthma care.
                                 ______
                                 
               Questions Submitted by Senator Jerry Moran
                   accelerating medicines partnership
    Question. The Accelerating Medicines Partnership (AMP) is expected 
to address the ``valley of death'' in drug development. How much with 
the Partnership shorten the current drug development timeline and how 
much money will be saved?
    If the Accelerating Medicines Partnership is successful, how will 
you determine what future disease and conditions will be added to the 
program?
    Answer. The Accelerating Medicines Partnership (AMP) is a unique 
type of public-private partnership of the National Institutes of Health 
(NIH), the Food and Drug Administration (FDA), nonprofit organizations, 
and biopharmaceutical companies. AMP is supporting research focused on 
identifying and validating biological targets for new therapeutics, a 
process called target validation. AMP was just launched in February and 
is beginning with three specific pilot projects, in Alzheimer's 
disease, type 2 diabetes, and rheumatoid arthritis/lupus.
    Over half of drugs fail in phase II and phase III clinical trials 
due to lack of efficacy, and improvements in the target validation 
process should reduce that failure rate. So while AMP may not affect 
the development timeline for a particular drug, it should increase the 
success rates of trials by increasing the chances that a particular 
drug will be effective. If AMP succeeds in validating a drug target for 
a particular disease, that could reduce drug development costs in that 
area, since companies should be less likely to conduct costly clinical 
trials with compounds that will fail in phase II or III because the 
targets of those compounds don't have the desired effect on the 
particular disease.
    The AMP partners intend to consider other project ideas later this 
year. As in the selection of the pilot projects, the AMP partners would 
need to agree that there is a scientific opportunity in target 
validation in a particular disease area with these characteristics: the 
research project would be amenable to a public-private partnership with 
joint scientific planning and governance; data would be shared broadly 
and not be patented; and industry or research foundations would be 
willing to commit substantial financial and other support. The 
Foundation for the NIH has a project proposal form on its Web site at 
http://fnih.org/work/key-initiatives-0/accelerating-medicines-
partnership to guide interested parties in developing project proposals 
for the AMP members to consider, and the AMP partners will also 
continue identifying and exploring their own areas of mutual scientific 
interest.
                           darpa-like program
    Question. I am concerned that researchers are now reluctant to take 
risks because of their concern that their research efforts will not be 
supported. How will NIH's new DARPA-like program address this concern?
    The new DARPA-like Program is funded at $30 million and would 
support high risk, goal-driven activities aimed to achieve rapid 
technology development. While I support this type of research, I am 
concerned that the funding for the new program is coming from another 
program that supports exceptionally creative scientists proposing 
innovative and transformative research--High-Risk High-Reward Research. 
The High-Risk High-Reward Research program's funding is reduced by 
$21.8 million. If funding ``maverick'' science is a priority for NIH, 
why does the budget cut one high risk research program's funding to 
start a new one?
    The Guardian ran a letter in March from a group of prominent 
researchers promoting additional funding to support scientific 
mavericks. The letter stated, ``Agencies claiming to support blue-skies 
research use peer review, of course, discouraging open-ended inquiries 
and serious challenges to prevailing orthodoxies.'' In a time when 
budget resources are constrained, how do you balance funding for high-
risk research projects with peer-reviewed science?
    Answer. Scientific progress often advances by building 
incrementally upon a strong foundation of previous research and 
preliminary data. However, rapid advances in progress may require 
approaches that foster innovation and risk taking. For certain 
objectives, where research teams need to be actively managed to achieve 
defined, high-risk goals so that new expertise can be added as initial 
high-risk attempts fail or as new discoveries are made, the DARPA-like 
Other Transaction Authority (OTA) provided to the Common Fund can be 
very helpful. The NIH Common Fund's Stimulating Peripheral Activity to 
Relieve Conditions (SPARC) program will use the OTA to support a high-
risk, goal-driven endeavor to develop proof of concept for an entirely 
new class of neural control devices that have the potential to 
precisely treat a wide variety of diseases and conditions. 
Neuromodulation to control end-organ system function has been 
recognized as a potentially powerful way to treat many diseases and 
conditions, such as hypertension and heart failure, gastrointestinal 
disorders, diabetes, and inflammatory disorders. However, the 
mechanisms of action for neuromodulation therapies are poorly 
understood. The SPARC program will support interdisciplinary teams of 
investigators to deliver neural circuit maps of several organ systems, 
novel electrode designs, minimally invasive surgical procedures, and 
stimulation protocols, driven by an end goal to develop new 
neuromodulation therapies. The program is expected to be iterative and 
dynamic, with the novel technologies informing mapping efforts, and 
mapping results defining new technology requirements. Rapid progress in 
this nascent field requires high levels of innovation and risk taking 
as well as aggressive project management to achieve these ambitious 
goals and capitalize on the therapeutic promise of this emerging 
research area.
    In addition to the SPARC program, several other initiatives within 
the Common Fund specifically support high-risk research. The High-Risk 
High-Reward program, which includes the Pioneer, New Innovator, 
Transformative Research, and Early Independence Awards, supports 
exceptionally creative scientists to undertake bold and innovative 
research projects in any scientific area relevant to the NIH mission. 
For these projects, NIH has no pre-defined objective other than to 
foster innovative, exceptionally high-impact research through 
investigator-initiated projects. Therefore, for these projects, a grant 
mechanism, rather than the OTA mechanism, is most useful. Although 
Common Fund support for the High-Risk High-Reward program decreases in 
fiscal year 2015, the successful track record of the High-Risk High-
Reward program has moved NIH's Institutes and Centers to increase their 
support of these awards, providing additional funding beyond the Common 
Fund investment.
    All NIH-supported research, including programs designed to support 
high-risk research, undergoes a rigorous peer-review process to 
identify the most scientifically meritorious projects. Programs 
designed to support high-risk research may emphasize different criteria 
during peer review compared to more traditional grant mechanisms, 
weighting innovation and potential impact more heavily than feasibility 
and preliminary data. Highly innovative ``blue skies'' research and 
peer review are not mutually exclusive. Although the specific review 
processes for SPARC and other OTA programs may be different from grant 
or contract reviews, external input will still be sought to help guide 
the decisionmaking process.
    The question of how to balance funding for high-risk research with 
research that is more grounded by preliminary data is perennial, and 
the answer varies across the NIH as scientific opportunities and 
challenges vary between fields of research. However, risk tolerance is 
a founding principle of the NIH Common Fund so that innovative 
solutions to the most pressing challenges may be reached.
               clinical and translational science awards
    Question. How has NCATS implemented the Institute of Medicine's 
Clinical and Translational Science Awards (CTSA) recommendations and 
how do you see the program growing over the next several years?
    Answer. In June 2013, the Institute of Medicine (IOM) issued a 
report following a review of the Clinical and Translational Science 
Awards (CTSA) Program. The report recommended that the National Center 
for Advancing Translational Sciences (NCATS) take a more active role in 
the program's governance and direction, formalize the evaluation 
processes of the program, advance innovation in education and training 
programs, and ensure community engagement in all phases of research.
    NCATS leadership is committed to implementing the recommendations 
of the IOM report. As a first step, NCATS has increased the 
programmatic and fiscal management of the grants that support this 
program and streamlined the way the consortium is governed, consulting 
closely with the CTSA Principal Investigators (PIs). For example, we 
have appointed a new steering committee that includes 12 CTSA PIs with 
staggered terms to replace the previous 90-member group.
    In parallel, NCATS assembled a Working Group of its Advisory 
Council to provide advice on measurable objectives for the CTSA 
program. The group was tasked with developing clear, measurable goals 
and objectives for the program that address critical issues across the 
full spectrum of clinical and translational research (i.e. ``what does 
success look like?''). The Working Group presented its report (http://
www.ncats.nih.gov/files/CTSA-IOM-WG-Draft-Report.pdf) at the NCATS 
Advisory Council meeting in May. Its report addressed four of the seven 
recommendations in the IOM report and focused on: (1) translational 
workforce development, (2) engagement and collaboration with patients 
and communities, (3) integration of translational science across its 
multiple phases and disciplines within complex populations and across 
the individual lifespan, and (4) systemic improvements in methods and 
processes of translation. The measurable goals and outcomes in this 
report are serving as a guide for NCATS as it moves forward in 
developing and implementing strategies to strengthen the CTSA program 
and for measuring progress.
    NCATS recently announced the selection of Petra Kaufmann, M.D., 
M.Sc., to head the NCATS Division of Clinical Innovation, which 
includes the CTSA program. Dr. Kaufmann served as Director of the 
Office of Clinical Research at NIH's National Institute of Neurological 
Disorders and Stroke (NINDS) and brings a wealth of expertise across 
the translational sciences spectrum.
    With the appointment of a permanent Director for the program, the 
recommendations of the IOM report, and the results of deliberations by 
the Advisory Council and its working group, NCATS is poised to work 
closely with the CTSA community to improve the effectiveness and 
efficiency of the process of translation from scientific discovery 
through clinical research to improved health outcomes.
   brain research through application of innovative neurotechnologies
    Question. We discussed the Brain Research through Application of 
Innovative Neurotechnologies (BRAIN) Initiative at last year's budget 
hearing. This is an exciting proposal that could revolutionize the 
field of neuroscience and advance therapies for numerous diseases, 
including Alzheimer's. The subcommittee provided funding for this 
initiative in fiscal year 2014 and requested a report on the goals, 
objectives, budget, and timeline for the BRAIN Initiative. Could you 
elaborate on the commitment we are undertaking and provide specific 
details on what the 10 year budget picture may entail?
    Answer. NIH charged a high-level working group of the Advisory 
Committee to the Director (ACD) to develop a rigorous plan for the 
Initiative that includes scientific milestones and budgetary 
projections (roster at http://www.nih.gov/science/brain/acd-
roster.pdf). This working group comprised visionary leaders across 
neuroscience disciplines that were expertly positioned to delineate 
bold, yet achievable, multi-year timetables, milestones, and cost 
estimates. Over the last year, the working group met with the 
scientific community, patient advocates, and the general public to 
ensure its plan would be sufficiently informed by stakeholder input.
    The working group delivered its final report for consideration by 
the ACD at its June 5-6 meeting. The scientific vision outlined in this 
report was unanimously supported by the Committee and subsequently 
endorsed by the NIH Director. In its findings, the group emphasized 
that the NIH efforts on the BRAIN Initiative should seek to map the 
circuits of the brain, measure the fluctuating patterns of electrical 
and chemical activity flowing within those circuits, and understand how 
their interplay creates our unique cognitive and behavioral 
capabilities. The following seven scientific goals were identified as 
high priorities for achieving this vision:
      1. Identify and provide experimental access to the different 
        brain cell types to determine their roles in health and 
        disease.
      2. Generate circuit diagrams that vary in resolution from 
        synapses to the whole brain.
      3. Produce a dynamic picture of the functioning brain by 
        developing and applying improved methods for large-scale 
        monitoring of neural activity.
      4. Link brain activity to behavior with precise interventional 
        tools that change neural circuit dynamics.
      5. Produce conceptual foundations for understanding the 
        biological basis of mental process through development of new 
        theoretical and data analysis tools.
      6. Develop innovative technologies to understand the human brain 
        and treat its disorders; create and support integrated brain 
        research networks.
      7. Integrate new technological and conceptual approaches produces 
        in Goals 1-6 to discover how dynamic patters of neural activity 
        are transformed into cognition, emotion, perception, and action 
        in health and disease.
    These scientific goals will be maximized through seven core 
principles:
      1. Pursue human studies and non-human models in parallel.
      2. Cross boundaries in interdisciplinary collaborations.
      3. Integrate spatial and temporal scales.
      4. Establish platforms for preserving and sharing data.
      5. Validate and disseminate technology.
      6. Consider ethical implications of neuroscience research.
      7. Create mechanisms to ensure accountability to NIH, the 
        taxpayer, and the community of basic, translational, and 
        clinical neuroscientists.
    The first year of the BRAIN Initiative, fiscal year 2014, was 
seeded by a $40 million commitment from NIH. The President has 
requested $100 million in his fiscal year 2015 budget for the second 
year of the Initiative. For the remaining years, the working group 
suggests an investment ramping up to $400 million a year for fiscal 
years 2016-2020 to focus on technology development and validation. They 
called for $500 million a year for years 2021-2025 to focus 
increasingly on the application of those technologies in an integrated 
fashion to make fundamental new discoveries about the brain. The 
working group emphasized that its cost estimates, which are 
provisional, assume that the budget for the BRAIN Initiative will 
supplement--not supplant--NIH's existing investment in the broader 
spectrum of basic, translational, and clinical neuroscience research.
    A full copy of the report can be found at http://www.nih.gov/
science/brain/2025/index.htm.
                          alzheimer's funding
    Question. Historically, NIH has opposed disease specific funding to 
allow research, not politics, to drive scientific funding decisions. 
However, this appears to cause a chicken and egg scenario. It is 
difficult for scientists to propose Alzheimer's research when there is 
not a robust funding stream to support their work, yet there is not a 
robust funding stream because scientists may not be proposing 
Alzheimer's research projects. So which comes first? The dedicated 
funding stream or the research ideas?
    Answer. NIH develops targeted funding initiatives to address areas 
of scientific need and opportunity as identified by program staff in 
consultation with experts in the scientific community. The resulting 
initiatives are strategically deployed to make every dollar count by 
establishing priorities, setting goals that are both ambitious and 
realistic, and identifying the most promising opportunities for 
progress through careful planning, coordination, and resource 
allocation.
    Although these targeted initiatives have enabled us to support a 
number of groundbreaking projects, it is important to note that the 
bulk of NIH's funding, in Alzheimer's disease and elsewhere, goes to 
investigator-initiated proposals--that is, proposals that are not 
developed in response to a specific funding initiative. For example, in 
fiscal year 2013, fewer than 10 percent of NIH's Alzheimer's-related 
research project grants were awarded under an Alzheimer's-specific 
funding opportunity announcement (FOA). The majority of Alzheimer's-
related studies were either awarded under a more general neuroscience-
focused FOA or an FOA in a related area, or were truly investigator-
initiated studies reflecting the creativity and innovation of 
researchers seeking to build on scientific advances or offering new 
ways of thinking about the disease.
    The importance of Alzheimer's disease research within the overall 
NIH research portfolio continues to be reflected in our strategic 
planning process and scientific funding initiatives. Our Alzheimer's-
related funding opportunity announcements (FOAs) are carefully 
developed to advance the field consistent with the priorities 
established under the National Action Plan for Alzheimer's Disease and 
the 2012 Alzheimer's Disease Research Summit. In addition, in the past 
5 years NIH has released over 40 FOAs directly relevant to Alzheimer's, 
and the response to each of these has been robust. In fact, each year 
we receive many more applications for meritorious research in 
Alzheimer's disease than we are able to fund.
    Question. How do you prioritize funding for a disease when you 
know, as in the case of Alzheimer's disease, that the disease burden is 
only going to increase over the next 20 years?
    Answer. Priority-setting processes at both the NIH and individual 
Institute levels are designed to maintain a balance among a wide array 
of diverse and compelling priorities, based on close monitoring of the 
scientific and medical landscapes by expert program staff and outside 
advisors. This enables us to use our funds efficiently and effectively 
in order to have the optimal impact both on the scientific field and on 
the public health. Alzheimer's disease is one such high-priority 
research area. Our planning, priority-setting, and funding initiatives 
fully take into account the projected increase in disease burden in 
this area.
    The NIH Director is responsible for program coordination across the 
NIH Institutes and Centers (ICs) and for ensuring a balanced overall 
research portfolio. In turn, each IC has a process for establishing 
research and funding priorities based on its specific mission and the 
long-term research goals articulated within relevant strategic plans. 
These priorities are reflected in the ICs' plans to distribute 
resources.
    To ensure that these priorities are harmonized with the wider NIH 
mission, the NIH Director provides centralized coordination and 
communication across NIH. During biweekly meetings with the IC 
Directors, the NIH Director considers the entire biomedical research 
landscape and discusses with his colleagues ways that NIH can be most 
effective with its investments. They hear from innovative scientists 
about cutting-edge results and deliberate potential new initiatives 
that could significantly advance the science in a particular field.
    NIH receives input from many sources when setting research and 
funding priorities for Alzheimer's. In addition to scientific 
workshops, international conferences, and other interactions with the 
scientific community, these sources include the National Advisory 
Council on Aging and the Advisory Council on Alzheimer's Research, 
Care, and Services, established under the 2011 National Alzheimer's 
Project Act. In addition, input from the 2012 Alzheimer's Disease 
Research Summit and the 2013 workshop on Alzheimer's Disease-Related 
Dementias has been instrumental in facilitating the development of our 
Alzheimer's research agenda.
                                 ______
                                 
               Question Submitted by Senator Thad Cochran
                          jackson heart study
    Question. Dr. Collins, the Jackson Heart Study, located in Jackson, 
Mississippi, is the largest-ever investigation of cardiovascular 
disease in African Americans. In the National Heart, Lung and Blood 
Institute's congressional budget justification for this year, one of 
your focuses is on preventing and pre-empting chronic heart, lung, 
blood and sleep disorders. Can you tell me how the Jackson Heart 
Study's recent collaboration with the Framingham Heart Study can be 
leveraged to specifically address this particular theme?
    Answer. Since it began in 1998, the Jackson Heart Study (JHS) has 
provided extensive information on the causes of cardiovascular disease 
in African Americans. JHS is also one of the largest studies of the 
genetic factors that affect high blood pressure, heart disease, stroke, 
diabetes, and other diseases that disproportionately affect African 
Americans. A recent JHS-related paper, for example, showed that the 
gene APOL1, which is known to contribute to chronic kidney disease, was 
found to also increase risk of cardiovascular disease in African 
Americans. Genetic analyses such as this provide promise for targeted 
therapies that can pre-empt disease. In August 2013, NHLBI contracts 
supporting the JHS were renewed for another 5 years.
    A new collaborative research relationship has been established 
between the American Heart Association (AHA) and the University of 
Mississippi and Boston University, the academic coordinating center 
homes of the JHS and Framingham Heart study (FHS), respectively. The 
AHA-led study, called the Cardiovascular Genome Phenome Study (CVGPS), 
will expand upon the research taking place within the Framingham and 
Jackson Heart studies by investing in parallel genomic and genetic 
analyses among other research subjects, expanding diversity and 
enhancing new approaches to find more ``personalized'' treatment and 
prevention interventions that could pre-empt chronic cardiovascular 
disease and other conditions. The CVGPS will also seek to make new data 
available for analysis by qualified investigators.
    More generally, NHLBI is taking the necessary steps to transform 
its epidemiology research efforts in a way that builds on emerging 
scientific tools and data platforms. NHLBI has established an Advisory 
Council Working Group on Epidemiology Research to strategically examine 
how to maximize the potential of our epidemiological studies by joining 
complementary data across cohorts such as the FHS and the JHS for new 
scientific investigations. Leveraging our available resources, through 
strategic partnerships and collaborations, offers the best hope to 
address critical needs that will not only improve treatment but also 
change the course of disease before irreversible consequences occur.
                                 ______
                                 
            Questions Submitted by Senator Richard C. Shelby
           science, technology, engineering, and mathematics
    Question. The fiscal year 2015 budget request, once again, proposes 
a reorganization of science, technology, engineering, and mathematics 
(STEM) education. While the STEM proposal kept the Science Education 
Partnership Awards program at NIH, the budget proposes to eliminate 
four other STEM initiatives throughout the agency. What metrics were 
used to decide these programs should be eliminated?
    Answer. The President's budget for fiscal year 2015 proposes a 
reorganization of all Federal Science, Technology, Engineering, and 
Mathematics (STEM) education programs. Consistent with the Government-
wide STEM reorganization, NIH decided to phase out four of its smaller 
STEM programs and notified grantees of the discontinuation of future 
new STEM programs supported by the National Institute on Drug Abuse 
(NIDA), the National Institute of Environmental Health Science (NIEHS), 
the National Institute of Neurological Disorders and Stroke (NINDS), 
and the National Institute of Allergies and Infectious Diseases 
(NIAID). This decision to discontinue or eliminate these programs 
follows the recommendations of the Federal STEM Education 5-Year 
Strategic Plan (Appendix Table A6: STEM Education Funding in Millions 
by Agency, page 98). Consistent with the report language accompanying 
the Consolidated Appropriations Act, 2014 (Public Law 113-76), NIH is 
continuing support of the Science Education Partnership Award program 
and the Office of Science Education.
               clinical and translational science awards
    Question. Dr. Austin, can you tell me how the Clinical and 
Translational Science Awards (CTSA) program is helping underserved 
populations, for example in my home state of Alabama, and in other 
underserved states in the Deep South?
    Answer. The University of Alabama at Birmingham (UAB) CTSA began a 
new program in 2010 called, ``The Deep South Network for Translational 
Research (DSNTR).'' It involves the UAB CTSA as the organizing hub, 
with participation of other institutions in the Deep South that do not 
have a CTSA including, Louisiana State University, Tulane University, 
Tuskegee University, University of Alabama-Tuscaloosa, University of 
South Alabama, and University of Mississippi Medical Center. It makes 
the sophisticated research capabilities of UAB available to 
investigators at these other institutions for use in multi-
institutional collaborative research projects, especially those that 
focus on underserved populations. Further, in collaboration with 
Alabama's Historically Black Colleges and Universities, the UAB CTSA 
has built an extensive network for training the next generation of 
health disparities researchers.
    The University of Arkansas Translational Research Institute (TRI) 
aims to translate successful healthcare research projects directly to 
patient care delivery regardless of where they live. The TRI partners 
with key community organizations across the state to facilitate 
research contacts and clinical care connections among rural and 
medically underserved populations. The TRI has leveraged and built upon 
Arkansas' statewide telemedicine program, in particular the Antenatal 
and Neonatal Guidelines, Education, and Learning System (ANGELS) 
program, which links obstetricians across the state to UAMS maternal-
fetal medicine specialists. Its partnership with the Tri-County Rural 
Health Network has connected elderly and adult disabled citizens with 
home and community-based services as alternatives to nursing homes. 
Finally, a nascent partnership with the Philips County Faith Task Force 
has enabled development of a community-based program for rural veterans 
in Jefferson County to build capacity to conduct participatory 
research. The project's overarching goal is to establish a community-
linked infrastructure that will increase minority participation in 
translational research intended to reduce racial and ethnic health 
disparities.
    At the Atlanta CTSA, experts in community engagement seek out 
community healthcaregivers that can articulate the heath needs of the 
local population, especially those who face disproportionately higher 
health risks. The Atlanta CTSA includes Emory University, the Georgia 
Institute of Technology, and the Morehouse School of Medicine, which is 
dedicated to improving the health and well-being of individuals and 
communities with emphasis on the underserved urban and rural 
populations in Georgia. Morehouse provides leadership in developing 
programs that specifically address healthcare needs in the Atlanta 
region. Examples include ``e-Healthy Strides,'' which partnered with 
Big Bethel AME Church to collect health data and transmit it to the 
parishioners' physicians; ``i-Adapt,'' a program designed to provide 
instruction and motivation to people with diabetes to facilitate self-
care; and EPICS (Educational Program to Increase Colorectal Cancer 
Screening), a program aimed at teaching primary healthcare teams about 
screening more effectively for colorectal cancer.
                   accelerating medicines partnership
    Question. Under the new Accelerating Medicines Partnership program, 
rheumatoid arthritis and lupus will receive $41.6 million in research 
funding over 5 years, with about half of this funding coming from the 
NIH and half from pharmaceutical companies. I am concerned that the 
funding for lupus is not new NIH funds, but redirected funding from 
current research projects. Are you concerned that AMP is taking away 
from current lupus research resources as opposed to allocating 
additional resources towards lupus?
    Will data generated as a result of the Accelerated Medicines 
Partnership be available to other scientists studying these diseases?
    What other diseases and conditions will this program be supporting 
in the future?
    Answer. The Accelerating Medicines Partnership (AMP) is a unique 
type of public-private partnership of the National Institutes of Health 
(NIH), the Food and Drug Administration (FDA), nonprofit organizations, 
and biopharmaceutical companies. AMP is supporting research focused on 
identifying and validating biological targets for new therapeutics, a 
process called target validation. AMP was just launched in February, 
and as noted, is beginning with three specific pilot projects, 
including a rheumatoid arthritis and lupus project.
    The AMP program offers an exceptional opportunity to leverage NIH 
investments in lupus research with substantial funds and intellectual 
support from industry and non-profit organizations. Recognizing the 
need and opportunity, NIH, after consulting with the research 
community, released two Requests for Applications (RFAs) to implement 
the AMP program in lupus and rheumatoid arthritis. The RFAs will not 
take money away from existing lupus projects. We expect that a number 
of researchers studying lupus will apply and be funded through the AMP.
    Because a major goal of the AMP is to generate pre-competitive, 
disease-specific data that will be accessible to the broad biomedical 
community, the program will also facilitate research by lupus 
investigators not funded through the AMP. AMP partners have also agreed 
that the research findings should not be patented.
    The AMP partners intend to consider other project ideas later this 
year. As in the selection of the pilot projects, the AMP partners would 
need to agree that there is a scientific opportunity in target 
validation in a particular disease area with these characteristics: the 
research project would be amenable to a public-private partnership with 
joint scientific planning and governance; data would be shared broadly 
and not be patented; and industry or research foundations would be 
willing to commit substantial financial and other support. The 
Foundation for the NIH has a project proposal form on its Web site at 
http://fnih.org/work/key-initiatives-0/accelerating-medicines-
partnership to guide interested parties in developing project proposals 
for the AMP members to consider, and the AMP partners will also 
continue identifying and exploring their own areas of mutual scientific 
interest.
                                 ______
                                 
              Question Submitted by Senator Lindsey Graham
                        breast cancer screening
    Question. From 1990 to 2010, deaths from breast cancer decreased by 
34 percent. However, in 2013, 230,000 new cases of breast cancer were 
diagnosed in the United States and almost 40,000 women died from breast 
cancer.
    Recent news coverage has focused on studies that called into 
question the value of screening for breast cancers. Although the 
majority of scientific studies have corroborated the value of early 
detection of breast cancers through screening, these recent articles 
have created a less clear picture of the benefits of screening and may 
lead women to avoid periodic mammography, an experience some women 
already view as uncomfortable.
    Given these current controversies, do you think the NCI should 
undertake a new study to clarify the benefits of screening so that 
women and their doctors will have a better idea of how breast cancer 
screening should fit into a woman's overall preventative health 
program?
    Answer. We are aware of the growing concerns about the balance of 
benefits and harms associated with screening mammography. Some of these 
concerns have recently been outlined by the Swiss Medical Board in its 
recommendation to end the national Swiss breast cancer screening 
program (Reference: Biller-Andorno N and Juni P: N Engl J Med 
2014;3760:1965-1967). The concerns fall into two categories. First, the 
reduction in cancer mortality by early detection of breast cancer using 
mammography may decline as more effective adjuvant chemotherapy has 
been developed for treatment of early- and mid-stages of breast cancer. 
(Much of this unequivocal progress in treatment came from NCI-sponsored 
randomized trials of adjuvant therapy.) Nearly all of the randomized 
trials testing the efficacy of mammography were conducted decades ago, 
in the pre-adjuvant therapy era. A recently reported and widely 
publicized Canadian trial started early in the era of adjuvant therapy 
and showed no reduction in breast cancer mortality associated with 
mammography screening as opposed to screening by physical examination 
(Reference: Miller AB, et al.: BMJ 2014; doi: 10.1136/bmj.g366). 
Second, new evidence of harms associated with mammography has emerged 
in recent years, particularly one known as overdiagnosis--the detection 
of non-life threatening tumors that caused anxiety and were treated 
with measures that carry risks, such as surgery, radiation, and 
chemotherapy (Reviewed in: Pace LE and Keating NL: JAMA 2014;311:1327-
1335).
    The emerging evidence has led to calls for additional studies in 
the current modern era of breast cancer therapy that would clarify the 
balance of benefits and harms of breast cancer screening. The ideal or 
``gold standard'' test would be a large randomized trial comparing 
screening mammography to a control group that does not receive 
screening mammography, but such a study would not be feasible in the 
United States. National surveys show that a large proportion of 
American women continue to get routine screening mammography, with no 
change in usage after the U.S. Preventive Services Task Force issued 
its recommendations against routine screening for women ages 40-49 and 
for spacing mammography for women age 50-74 from annually to every 2 
years (Reference: Pace LE, et al.: Cancer 2013;119:2518-2523). Given 
current practice, a true control group for an optimally informative 
``gold standard'' trial appears to be impossible.
    Therefore, NCI is actively funding and planning other types of 
studies to learn more about the benefits and harms of breast cancer 
screening, and to try to maximize any benefits while limiting the 
harms. First, NCI is taking several approaches to improve on the 
benefits of mammography as currently practiced. NCI funds a multi-
institutional Breast Cancer Screening Consortium, a collaborative 
network of seven research registries designed to track outcomes of 
screening mammography in the community, including recall and biopsy 
rates, and tumor stages at diagnosis. A goal is to explore ways to 
achieve optimal and reproducible mammography reading in the community. 
A recently developed inter-divisional NCI request for applications 
(RFA) will focus on studying the process of screening and subsequent 
therapy, with a focus on overdiagnosis, which, as noted above, often 
leads to inappropriate and potentially harmful treatment. This project 
will compare tumor biology and clinical aggressiveness with the method 
of detection, including breast imaging, and with the criteria used for 
diagnosis. The research aims to identify ways to ensure timely follow-
up of abnormal findings and institution of effective therapy when 
necessary.
    Additionally, in an effort to minimize the harms of overdiagnosis, 
several other methods for screening are under investigation. The Early 
Detection Research Network (EDRN) is studying new methods to identify 
the molecular ``fingerprints'' of screen-detected tumors with little 
lethal potential, so that more patients can be followed without 
institution of unnecessary aggressive treatments. A funding opportunity 
announcement (FOA) for a consortium of multidisciplinary scientists 
specifically focused on identification of early screen-detected ``non-
progressor'' lesions that can be safely followed is under 
consideration, with breast cancer as one of the four primary areas of 
emphasis of the proposed consortium.
    A related research area involves the study of other imaging 
modalities to detect breast cancer. The balance of benefits and harms 
of breast MRI in the general population is not known, so it is not 
usually considered to be suited to general screening. However, some 
experts have recommended it as an adjunct screening tool for women at 
extremely high risk of breast cancer, such as women who have high-risk 
inherited mutations of their BRCA 1 or 2 genes, a history of ionizing 
radiation treatments to the chest (administered to treat other 
malignancies), or a family history of breast cancer. The screening 
recommendations for these women include both an annual mammogram and 
MRI for the BRCA mutation carriers and an optional MRI or ultrasound 
for the rest. (An update on breast cancer screening and prevention. 
Cruz MS, Sarfaty M and Wender RC; Primary Care: Clinics in Office 
Practice Vol. 41, Issue 2, June 2014, Pages 283-306.).
    FDA has approved digital breast tomosynthesis or 3-D mammography 
devices, which use low dose x-rays for breast cancer screening but 
experts do not agree on its clinical use. A few small studies have 
shown that adding digital breast tomosynthesis to standard mammography 
screening may result in a significant reduction in patients being 
recalled for additional testing compared to routine screening 
mammography alone, but more research is needed. NCI is considering 
potential studies to see if breast tomosynthesis can improve 
sensitivity and lower recall rates.

                          SUBCOMMITTEE RECESS

    Senator Harkin. Thank you very much.
    [Whereupon, at 11:55 a.m., Wednesday, April 2, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]