[Senate Hearing 113-]
[From the U.S. Government Publishing Office]
DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND
RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2014
----------
WEDNESDAY, MAY 15, 2013
U.S. Senate,
Subcommittee of the Committee on Appropriations,
Washington, DC.
The subcommittee met at 2:30 p.m., in room SD-138, Dirksen
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
Present: Senators Harkin, Mikulski, Moran, Cochran, Shelby,
and Boozman.
DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR
ACCOMPANIED BY:
ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY
AND INFECTIOUS DISEASES
GARY H. GIBBONS, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND
BLOOD INSTITUTE
RICHARD J. HODES, M.D., DIRECTOR, NATIONAL INSTITUTE ON AGING
STORY C. LANDIS, Ph.D., DIRECTOR, NATIONAL INSTITUTE FOR
NEUROLOGICAL DISORDERS AND STROKE
HAROLD E. VARMUS, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE
OPENING STATEMENT OF SENATOR TOM HARKIN
Senator Harkin. The Senate Appropriations Subcommittee on
Labor, Health and Human Services, and Education will please
come to order.
Today, we are privileged to have with us, again, as my
longtime compatriot Arlen Specter used to say, ``The crown
jewel of the Federal Government.'' That is our National
Institutes of Health (NIH) here today for our budget hearing.
So, Dr. Collins, we welcome you back to the subcommittee,
and also, in alphabetical order, Dr. Tony Fauci, Director of
the National Institute of Allergy and Infectious Diseases; Dr.
Gary Gibbons, Director of the National Heart, Lung, and Blood
Institute; Dr. Richard Hodes, Director of the National
Institute on Aging; Dr. Story Landis, Director of the National
Institute for Neurological Disorders and Stroke; Dr. Harold
Varmus, Director of the National Cancer Institute.
This is a perilous moment for NIH and, indeed, for the
future of biomedical research in this country. Since fiscal
year 2003, the end of the 5-year doubling effort, NIH funding
has dropped in real terms by 22 percent. In other words, the
purchasing power of NIH's appropriations has fallen by more
than one-fifth over the past decade.
This year, fiscal year 2013, NIH funding will drop in
actual dollars by $1.7 billion below last year's level, almost
entirely because of sequestration.
As a result, NIH will award 700 fewer new research project
grants this year than it did last. That means 700 fewer
opportunities to investigate and possibly find the cures for
cancer and Alzheimer's and diabetes and any number of diseases.
Perhaps even more alarming, a researcher's chance of
getting a grant approved by NIH will drop to just 16 percent.
That is the lowest success rate in the history of NIH.
That comes at the time when the potential for scientific
breakthroughs has perhaps never been better. At the National
Cancer Institute, the success rate will be just 12 percent. At
other institutes, below 10 percent. That's abysmal.
When you have less than a 1-in-10 chance of getting a
grant, that's when our best and brightest young minds start
asking, ``What's the point? Maybe I need to find a different
career.''
It's no wonder that some are saying our Nation's status as
the undisputed world leader in biomedical research is under
threat.
The President's budget request offers a welcome response to
this disturbing decline. His budget calls for $31.1 billion for
NIH in fiscal year 2014, which would not only reverse all of
the cuts that are occurring this year but result in an increase
over the fiscal year 2012 level. Included in that increase is
$40 million to the new Brain Research through Advancing
Innovative Neurotechnologies (BRAIN) Initiative, which I'm sure
we'll hear more about.
And I read your testimony last night, you mention that,
both Dr. Collins and, I'm sure, Dr. Landis.
So I want to do everything I can to help boost NIH's budget
this year. I suspect that many Senators on the other side of
the aisle also agree with this. NIH enjoys more bipartisan
support than perhaps any other Agency in the entire Labor-HHS
appropriations bill.
But here's a problem. At the same time some of my
colleagues are requesting a strong commitment to NIH funding,
they also want sequestration to continue in fiscal year 2014.
Some even want deeper cuts to nondefense discretionary spending
next year to pay for some more increases in defense spending.
There simply is no way to square these two priorities. I
can promise you, if sequestration stays in effect next year,
there's no chance that we will get close to the President's
request for NIH, let alone back to the fiscal year 2012 level.
It just won't happen.
We are not going to savage other functions in education,
health, labor, Centers for Disease Control and Prevention, and
others, which are already at minimal levels. I will not get
engaged in pitting NIH against other worthwhile endeavors in
this appropriations bill.
This is just one of the many reasons why we need to replace
sequestration with a mix of targeted, responsible spending
cuts, not just blind cuts to everything, and, yes, increased
revenue.
This sort of balanced approach is the only way NIH will
have the resources it needs to realize the enormous scientific
opportunities that we'll hear about shortly from our witnesses.
First, I'll yield to Senator Moran for his opening
statement.
STATEMENT OF SENATOR JERRY MORAN
Senator Moran. Mr. Chairman, thank you very much, and let
me thank you and your staff for the continual effort for us to
work together to find a path forward on a Labor-H bill. I very
much appreciate the attitude and approach that our staffs, and
you and I, are taking.
And I appreciate Dr. Collins and the other center directors
being here today. This is a highlight, I think, for our
subcommittee as we hear of some of the most recent and exciting
developments as we face the challenges that disease provides.
Science and research are the foundation of innovation,
growth in our economy, and the solution to a myriad of issues
that confront the health and well-being of our Nation. NIH
funding biomedical research is the catalyst behind many of the
advances that are now helping Americans live longer and
healthier lives.
Because of the Federal investment in biomedical research,
U.S. cancer rates are now falling 1 percent each year, with
each 1-percent decline saving our Nation about $500 billion.
The U.S. death rate from heart disease and stroke have
declined more than 60 percent in the last half century. And
between 1997 and 2006, the death rate among adults with
diabetes declined 23 percent.
However, health advances aside, and they are paramount, the
reduction of healthcare costs in the future may be one of the
most significant contributions to society that medical research
provides.
As baby boomers age, the cost of healthcare will continue
to increase. For example, a study led by the economists at the
RAND Corporation stated that the cost of dementia care is
projected to double over the next 30 years, surpassing
healthcare expenses for both heart disease and cancer. Without
a way to prevent or cure or effectively treat dementia, it will
be difficult, if not impossible, to rein in costs.
But science has confronted similar health challenges in the
past and has prevailed. In the mid-20th century, economists
predicted polio would cost taxpayers $100 billion a year to
treat patients in iron lung hotels. In the face of this
challenge, medical research produced a solution to this
devastating disease, and polio is now on the verge of being
eradicated worldwide.
In the next few years, we confront difficult spending
choices. And I believe we must prioritize our Federal
commitment to NIH. It is crucial that our next generation of
biomedical researchers, the ones who will develop better and
more cost-effective healthcare, remain in the scientific
research field.
Without adequate and sustained Federal support for medical
research, trainees will be driven from medical fields, or into
the arms of our global competitors.
Last year, China's Government pledged to increase basic
research investment by 26 percent and will contribute more than
$300 billion to biotechnology over the next 5 years.
PREPARED STATEMENT
In the last 5 years, China's percentage of science and
engineering degrees earned by university students was more than
double those earned here in the United States. Without
continued investment in NIH, we jeopardize our current
scientific progress, risk losing a generation of scientists,
and stunt our Nation's global competitiveness.
This is not a time to waver on America's commitment to NIH
and to the health of all Americans.
Mr. Chairman, thank you, and I look forward to working with
you on these priorities.
[The statement follows:]
Prepared Statement of Senator Jerry Moran
Thank you, Mr. Chairman. I appreciate Dr. Collins and the other
Center Directors being here today to discuss funding for the National
Institutes of Health (NIH).
Science and research are the foundation of innovation, growth in
our economy, and the solution to the myriad of issues that confront the
health and well-being of our Nation. NIH-funded biomedical research is
the catalyst behind many of the advances that are now helping Americans
live longer and healthier lives. Because of the Federal investment in
biomedical research, U.S. cancer death rates are now falling 1 percent
each year, with each 1-percent decline saving our Nation about $500
billion. U.S. death rates from heart disease and stroke have declined
more than 60 percent in the last half-century. Between 1997 and 2006,
the death rate among adults with diabetes declined by 23 percent.
However, health advances aside--and they are paramount--the
reduction of healthcare costs in the future may be one of the most
significant contributions to society from medical research. As baby
boomers age, the cost of healthcare will continue to increase. For
example, a study led by economists at the RAND Corporation stated that
the cost of dementia care is projected to double over the next 30
years, surpassing healthcare expenses for both heart disease and
cancer. Without a way to prevent, cure, or effectively treat dementia,
it will be difficult, if not impossible, to rein in costs. But science
has confronted similar healthcare challenges in the past and prevailed.
In the mid-20th century, economists predicted polio would cost
taxpayers $100 billion a year to treat patients in ``iron lung
hotels.'' In the face of this challenge, medical research produced a
solution to this devastating disease. Polio is now on the verge of
being eradicated worldwide.
In the next few years as we confront difficult spending choices, I
believe we must prioritize our Federal commitment to NIH. It is crucial
that our next generation of biomedical researchers, the ones who will
develop better and more cost-effective healthcare, remain in the
scientific research field. Without adequate and sustained Federal
support for medical research, trainees will be driven from the medical
field or into the arms of our global competitors. Last year, China's
Government pledged to increase basic research investment by 26 percent
and will contribute more than $300 billion into biotechnology over the
next 5 years. In the last 5 years, China's percentage of science and
engineering degrees earned by university students was more than double
those earned by U.S. students.
Without continued investment in the NIH we jeopardize our current
scientific progress, risk losing a generation of scientists, and stunt
our Nation's global competitiveness. This is not the time to waiver on
America's commitment to the NIH and the health of all Americans.
Thank you, Mr. Chairman.
Senator Harkin. Thank you very much, Senator Moran.
And we welcome back again Dr. Francis Collins, the 16th
Director of the National Institutes of Health, a physician and
geneticist noted for discoveries of disease genes and his
leadership of the Human Genome Project, of which he was the
director from 1993 to 2008. Dr. Collins received a B.S. from
the University of Virginia, his Ph.D. from Yale, and an M.D.
from University of North Carolina at Chapel Hill.
Dr. Collins, your statement will be made part of the record
in its entirety. And, again, the floor is yours. Please proceed
as you so desire.
SUMMARY STATEMENT OF DR. FRANCIS S. COLLINS
Dr. Collins. Well, good afternoon, Mr. Chairman and members
of the subcommittee. I'm very pleased to be here with my
colleagues to present the President's budget request for the
National Institutes of Health for fiscal year 2014.
This panel has a long history of supporting NIH's mission
to seek fundamental knowledge and apply it in ways that enhance
human health, lengthen life, and reduce suffering.
My sincere thanks to you, Mr. Chairman, for your strong
commitment to supporting biomedical research over these years.
NIH and millions of patients are grateful for that leadership.
But I'm here today to talk about the Administration's
fiscal year 2014 budget request of $31.331 billion, which is a
$471 million, or 1.5 percent, increase over fiscal year 2012.
This budget request will enhance NIH's ability to support
cutting-edge research and training of the scientific workforce,
with the ultimate goal of speeding up development of new ways
to improve human health.
This request allocates resources to areas of extraordinary
promise while allowing flexibility to pursue unplanned
scientific opportunities and address unforeseen health needs.
But even with these tremendous scientific opportunities
before us, and our hopes for your support in fiscal year 2014,
we cannot ignore the current fiscal situation. As the chairman
has just said, this is a perilous moment.
As you know, and despite this subcommittee's best efforts
to avert it, sequestration took effect on March 27. Frankly,
this has already dealt a devastating blow to NIH and to the
entire biomedical research enterprise.
We're absorbing a $1.7 billion cut to our budget--and
without action by this Congress, that will result, from the
sequester, in a loss of $19 billion over the next 10 years.
NIH PURCHASING POWER
This graph that I'm showing you shows in blue the
appropriated levels to NIH and the effects of inflation in
orange. So including the sequester, which you can see
identified by this red arrow, that leads to a significant
downturn in fiscal year 2013, and which we hope will turn back
up again with the President's budget proposal for 2014, almost
22 percent of the purchasing power for research has been lost
versus 10 years ago, as you stated, Mr. Chairman.
The consequences are stark. Look back at 2003. At that
point, as a direct result of the efforts of this subcommittee,
NIH was supporting a total of 38,216 research project grants.
Now, a decade later, with all the scientific opportunity in
front of us, that number has fallen by more than 3,300 grants.
And the drop is particularly severe in fiscal year 2013, where
we'll be funding 700 fewer new and competing research project
grants done in fiscal year 2012. Which of those grants might
have led to the next big discovery in cancer research or
launched a career of a promising young scientist? We will never
know.
The paradox of my directorship at this time of
unprecedented scientific opportunity, when we should be making
progress by leaps and bounds towards curing human disease, is
that our resources are suffering a historic downturn.
This cut in support in biomedical research in the U.S. is
particularly troubling when one considers the investments being
made in the rest of the world, as Senator Moran has referred
to.
WORLDWIDE INVESTMENT IN BIOMEDICAL RESEARCH
This bar graph is really quite striking, and I don't think
anyone can look at it without being troubled by its
significance. It shows the relative increases in support for
biomedical research by countries around the globe. And you will
notice the United States stands out on this graph in a very
troubling way.
Mr. Chairman, I cannot gloss over the severity of this
situation. The potential damage to scientific momentum,
economic growth, and morale is profound.
Despite these trying times, NIH has continued to pursue our
mission and has been accelerating scientific discovery in
several key areas, and I'd like to highlight a couple of those.
CANCER: DECREASE IN DEATH RATES
Let's consider cancer. One person dies from cancer every
minute in the United States. NIH research has contributed to
real progress with cancer death rates falling by 1 percent per
year for the last 15 years, as already cited by Senator Moran.
Economists estimate that each 1 percent drop is saving the U.S.
$500 billion, making this an extremely good investment. But we
are actually positioned to do much more.
THE CANCER GENOME ATLAS (TCGA)
The Cancer Genome Atlas, or TCGA, is a coordinated effort
to accelerate our understanding of the molecular basis of
cancer using dramatic advances in genome sequencing
technologies to carry out comprehensive analysis of more than
20 types of cancer. By identifying the molecular changes in a
cancer cell, as compared to a healthy cell of the same
individual, we are gaining a better understanding of the
driving forces behind the disease.
NIH-FUNDED RESEARCH MAJOR DEVELOPMENTS
For example, very recently, NIH-funded researchers reported
a major development. And in a study widely reported in the news
media, they discovered that the genetic profile of a deadly
form of uterine cancer closely resembles the profiles of the
most lethal ovarian and breast cancers. This result has
dramatic implications for prognosis and treatment.
And this breakthrough, and others like it, is leading to
the identification of new therapies tailored to the patient's
unique genetic profile that can empower personalized
interventions, and precision medicine instead of one-size-fits-
all chemotherapy.
STEM CELL ADVANCEMENTS
Another example of how NIH-supported research is advancing
biomedical discovery is in the area of stem cells. Induced
pluripotent stem cells, also known as iPS cells, are
revolutionizing the way we study disease. iPS cells are mature
cells typically derived from a patient's skin that researchers
can reprogram back to an immature state. These cells can then
be programmed into a wide variety of cell types, including
liver cells, neurons, or blood cells.
This means we can start with a skin biopsy from a patient
and then re-create that same individual's disease in a Petri
dish. We can learn molecular details about the disease and even
test potential drugs to see if they are likely to be safe and
effective. It may one day even be possible to use these cells
therapeutically. You can imagine how this might work, for
instance, for a disease of the blood, such as sickle cell
anemia. But we're not stopping there.
NEW INITIATIVES IN FISCAL YEAR 2014
I'd like now to focus on a landmark new scientific endeavor
that we're planning for fiscal year 2014. Neurological and
psychiatric disorders such as Alzheimer's disease, Parkinson's
disease, autism, schizophrenia, epilepsy, and traumatic brain
injury inflict a tremendous toll on society yet their
underlying pathology has remained largely unknown due to the
enormous complexity of the human brain.
This complexity, built on 86 billion neurons--that's what
you got up there--each with thousands of connections was once
thought to be beyond the reach of scientific understanding.
Today, however, tremendous strides in neuroscience have created
new opportunities for unlocking these mysteries and have placed
us in the position of proposing a truly bold new initiative.
BRAIN INITIATIVE
And so in fiscal year 2014, NIH will begin its support of
the Brain Research through Advancing Innovative
Neurotechnologies, B-R-A-I-N, the BRAIN Initiative. The goal of
this initiative is to accelerate the development and
application of new technologies that will enable researchers to
produce dynamic pictures of the brain that show how individual
brain cells and complex neural circuits interact, all at the
speed of thought.
To do that, we need to be able to record signals in much
greater numbers of brain cells at a much more rapid pace than
is currently possible. And while recent innovations like
functional magnetic resonance imaging (MRI) have contributed
substantially to our expanding knowledge of the brain,
significant breakthroughs on how we treat neurological and
psychiatric disease will require a new generation of tools.
By measuring activity at the scale of circuits and networks
in living organisms, we can begin to translate data into models
that will decode sensory experience, motor activity, and
potentially even memory, emotion, and thought. So how do we set
about doing this?
HUMAN CONNECTOME PROJECT
Another major NIH initiative has already laid the
groundwork for mapping the human brain, the Human Connectome
Project. This is an image, a noninvasive image, of a healthy
human being, using a new kind of MRI. This connectome depends
upon a dramatic set of advances in MRI scanning, giving this 3-
D picture of a wiring diagram of nerve cells in your brain.
Interestingly, this proves that you are more than just your
deoxyribonucleic acid (DNA). Environmental factors and life
experiences work in concert with genetics to create your unique
neural connections. And this is where the BRAIN Initiative
comes in. It is designed to develop technologies that are
capable of recording the activity of hundreds of thousands of
neurons in real time, allowing us to determine the way in which
brain circuits actually function.
BRAIN INITIATIVE: LONG-TERM PLAN
The BRAIN Initiative is ambitious, and the details of a
plan that will stretch over a decade or more are being worked
out. But we must begin now. The BRAIN Initiative will provide a
better understanding of the roots of human neurological
disorders, revolutionize the field of neuroscience, and set the
stage for major advances in diseases that will catalyze the
development of new treatments and cures.
DR. COLLINS' SUMMARY
So, to sum up, today I've told you about the tremendous
scientific progress we've already made and a few of the many
fantastic opportunities that lie on the horizon. However, I
need to drive home, again, the impact of sequestration.
Let me close by putting a human face on exactly who is at
risk during these trying fiscal times.
FUTURE OF YOUNG SCIENTISTS
I recently met with Dina, one of my former superstar
students, who spent 2 years working in my lab at NIH before
deciding to go on to graduate school. She's now finishing her
Ph.D. at MIT and has done spectacular work in developmental
biology. But she sees what is happening to biomedical research
in the United States, and she is sufficiently worried about her
own future to begin to consider other options quite seriously.
In fact, many of her contemporaries have begun looking for
options outside of science or outside of this country. She
wrote me these words after our recent meeting: ``Many of my
role models--top scientists with amazing ideas and the
potential to change the world--are unable to get funding. I
can't erase the fear that this is my future.''
PREPARED STATEMENTS
This is a defining moment. My fear is that we're putting an
entire generation of U.S. scientists at risk. And if they go
away, they won't come back.
Sequestration is compromising the future of biomedical
research and slowing improvement in the health of all
Americans.
So, thank you, Mr. Chairman. I look forward to answering
any questions you and this committee may have.
[The statements follows:]
Prepared Statement of Francis S. Collins, M.D., Ph.D.
Good afternoon, Mr. Chairman and distinguished members of the
subcommittee. I am Francis S. Collins, M.D., Ph.D., and I am the
Director of the National Institutes of Health (NIH). Accompanying me
today are: Anthony S. Fauci, M.D., Director of the National Institute
of Allergy and Infectious Diseases; Gary H. Gibbons, M.D., Director of
the National Heart, Lung, and Blood Institute; Richard J. Hodes, M.D.,
Director of the National Institute on Aging; Story C. Landis, Ph.D.,
Director of the National Institute for Neurological Disorders and
Stroke; and Harold E. Varmus, M.D., Director of the National Cancer
Institute.
It is an honor to appear before you today to present the
Administration's fiscal year 2014 budget request for the NIH.
NIH's mission is to seek fundamental knowledge about the nature and
behavior of living systems and to apply that knowledge to enhance human
health, lengthen life, and reduce illness and disability. I can report
to you that NIH leadership, employees, and grantees continue to believe
passionately in our mission.
NIH has been advancing our understanding of health and disease for
more than a century, and scientific and technological breakthroughs
generated by NIH-supported research are behind much of the gains this
country has enjoyed in public health. For example, deaths from heart
attack have fallen by more than 60 percent over the past 40 years;
deaths from stroke by more than 70 percent. HIV/AIDS treatment and
prevention may now enable us to envision the first AIDS-free generation
since this virus emerged more than 30 years ago. More than 90 percent
of children diagnosed today with the most common form of childhood
leukemia will survive. NIH research has given us vaccines for cervical
cancer, influenza, and meningitis. We can look forward to a future in
which advanced prevention and treatment strategies such as these allow
everyone to have a much better chance of living a long and healthy
life.
I would like to begin today by highlighting just a few areas in
which NIH-supported research is opening up extraordinary new
opportunities to improve the health of the American public.
Let's consider cancer. One person dies from cancer every minute in
the United States--that equates to 1,500 deaths every day, the
equivalent of five crashing jumbo jets.\1\ NIH research has contributed
to real progress, with cancer death rates falling by 1 percent per year
for the past 15 years--but we aim to do much more. With the National
Cancer Institute (NCI) and the National Human Genome Research Institute
(NHGRI) as leads, NIH established The Cancer Genome Atlas (TCGA) as a
coordinated effort to accelerate our understanding of the molecular
basis of cancer, using dramatic advances in genome sequencing
technologies to carry out comprehensive genomic analysis of more than
20 types of cancer. By identifying the molecular changes in a cancer
cell as compared to a healthy cell of the same individual, we are
gaining a better understanding of the driving forces behind the
disease. That is leading to identification of new drug targets, as well
as of subsets of disease with different responses to therapy that can
empower personalized interventions instead of one-size-fits-all
chemotherapy. As an example, a TCGA research network of investigators
recently identified promising new therapeutic targets in squamous cell
carcinoma of the lung, the second most common form of lung cancer,
including three families of enzymes that act as molecular switches.\2\
These findings lay the foundation for the development and
implementation of advanced diagnostics and treatments for squamous cell
cancer. Moreover, they underscore the value and promise of our Nation's
investment in TCGA.
Another new and exciting area of basic research is the Human
Microbiome Project. Microbes inhabit many parts of the human body and
have often had a bad reputation for causing sickness. But more often
than not, they actually contribute to the health of their human hosts.
In a 5-year endeavor supported by the NIH Common Fund, 200 scientists
at 80 institutions sequenced the genomes of bacteria from multiple body
sites of 250 individuals, with striking results. The research showed
that certain communities of bacteria help keep people healthy, whereas
others appear to make people more susceptible to disease.\3\ When the
bacterial population in the intestinal tract gets disrupted, chronic
conditions such as obesity can result; this new understanding may
provide us with novel ways to address this serious health threat. An
unexpected result from another NIH-funded study was that poor diet is
not the only contributor to malnutrition. In fact, a bad assortment of
microbes in the gut can conspire with a nutrient deficient diet to lead
to severe malnutrition.\4\
A final example I want to provide of how NIH-supported research is
accelerating scientific discovery is in the area of stem cells. Induced
pluripotent stem (iPS) cell technology is revolutionizing the way we
study disease, and holds the promise of dramatic advances in treatment.
iPS cells are patient-derived cells, typically from skin, that
scientists can reprogram back to an embryonic stem cell-like state.
These cells can then be induced to turn on specific sets of genes to
differentiate into a variety of cell types, including blood cells,
liver cells, or neurons. This means researchers can re-create a
patient's disease in a dish and screen drug compounds against the
cells--rather than the patient--to determine drug toxicity and
efficacy. But it's also possible that these cells could be used
therapeutically, especially if an individual's genetic misspellings
could be corrected in their own iPS cells, and then programmed and
delivered to a tissue where they are sorely needed. Recent NIH-funded
studies have developed copy-editing enzymes that are making it faster,
easier, and cheaper to correct genetic typos. In 2011, researchers used
a specially engineered copy-editing enzyme to find and correct the
mutation that causes sickle cell anemia using iPS cells derived from a
patient with the disease.\5\ Two very recent, groundbreaking
discoveries along this same avenue are the development of the next
generation methodology of ``find and replace'' enzymes that are making
it much simpler to copy-edit the genome.\6\ \7\
While these exciting findings have led to a much deeper
understanding of health and human disease, much more work needs to be
done in order to move these strategies and others like them out of the
lab and into the clinic--and to do so as quickly as possible. To this
end, the Administration's fiscal year 2014 budget request for the NIH
is $31.331 billion, $471 million above the fiscal year 2012 level. This
budget request reflects the President's and the Secretary's commitment
to improving the health of the Nation and to maintaining our Nation's
leadership in the life sciences. The request highlights investments in
innovative research that will advance fundamental knowledge and speed
the development of new therapies, diagnostics, and preventive measures
to improve public health.
The fiscal year 2014 budget request, a 1.5-percent increase over
fiscal year 2012, will enhance NIH's ability to support cutting-edge
research and training of the scientific workforce. Within the
Administration's fiscal year 2014 budget, we will continue to increase
Research Project Grants (RPGs), NIH's funding mechanism for
investigator-initiated research. NIH expects to support 10,269
competing RPGs in fiscal year 2014, an increase of 1,283 over fiscal
year 2012 levels. For fiscal year 2014, NIH anticipates funding a total
of 36,610 RPGs. The budget request allocates resources to areas of the
most extraordinary promise for biomedical research, while maintaining
the flexibility to pursue unplanned scientific opportunities and
address unforeseen health needs.
A major initiative for NIH in fiscal year 2014 will be in the area
of Alzheimer's disease research. As many as 5.1 million Americans
suffer this irreversible, progressive, and devastating brain disease
that slowly destroys cognitive functions including memory and the
ability to reason and think.\8\ At the same time, millions of American
families struggle with the physical, emotional, and financial costs of
caring for a loved one with Alzheimer's. A recently published NIH-
supported study found the costs of caring for people with dementia in
the United States in 2010 ranged from $157 billion to $215 billion.\9\
This disease is not just a burden on our health, but also a burden on
our economy.
NIH, with the National Institute on Aging (NIA) taking the lead,
currently supports a number of studies aimed at understanding,
diagnosing, preventing, and treating Alzheimer's disease. In fiscal
year 2014, NIA would plan to award a total of 591 new and competing
RPGs, an increase of 277 from fiscal year 2012. This includes an $80
million increase for Alzheimer's research.
A seminal finding that has recently generated a lot of excitement
is the discovery that the protein, tau, which appears to be in part
responsible for the cognitive decline in Alzheimer's patients, spreads
from neuron to neuron like an infection.\10\ This means that if
researchers could find a way to prevent cell-to-cell transmission,
perhaps by blocking tau with an antibody, the disease process could be
halted. There is also growing evidence that successful treatment of
Alzheimer's disease needs to happen very early in the course of the
disease, perhaps even before any symptoms have appeared at all. This
kind of Alzheimer's disease prevention is at the heart of new clinical
trials being conducted by scientists at the Dominant Inherited
Alzheimer's Network (DIAN), a NIA-funded international research
partnership. One of the investigational drugs being tested is a
monoclonal antibody that binds to certain forms of amyloid beta, a main
constituent of the signature plaques in Alzheimer's disease. Trying to
prevent Alzheimer's symptoms from ever occurring in individuals at very
high genetic risk is a new strategy--one that we are eager to pursue in
order to determine if early intervention can influence this terrible
disease.
With advancing scientific and technological capabilities, such as
genome sequencing machines and high resolution medical imagers,
biomedical researchers are generating huge amounts of data at an
unprecedented pace. The need to integrate and analyze massively complex
datasets is referred to as the Big Data challenge--a challenge that we
must overcome to gain a deeper understanding of disease and develop the
next generation of therapeutic targets.
Managing Big Data is a critical part of translating scientific
discoveries into clinical applications. To address this challenge, NIH
is developing the Big Data to Knowledge (BD2K) program, which will be
launched in fiscal year 2014. BD2K will support four programmatic
efforts: (1) facilitate the broad use and sharing of large, complex
biomedical data sets through the development of policies, resources and
standards; (2) develop and disseminate new analytical methods and
software; (3) enhance training of data scientists, computer engineers,
and bioinformaticians; and (4) establish Centers of Excellence to
develop generalizable approaches that address important problems in
biomedical analytics, computational biology, and medical informatics.
In fiscal year 2014, NIH will invest at least $40 million in the BD2K
program through the Common Fund, and each Big Data Center of Excellence
will be funded at $2 million to $5 million per year for 3 to 5 years.
As Big Data challenges in biomedical research are shared with other
areas of scientific research such as energy and space research, BD2K
will also require effective collaboration and coordination with other
Government agencies tackling similar challenges, including the National
Science Foundation and the Department of Energy, as well as privately
funded efforts. With the proper investments and efforts, we will
overcome the challenges associated with Big Data in order to accelerate
the translation of bench to bedside applications.
Another exciting new initiative I would like to tell you about is
NIH's efforts to recruit and retain a diverse pool of scientific talent
and creativity. NIH is strongly committed to maintaining a diverse
biomedical research workforce and has supported programs to enhance the
diversity of our workforce for more than 30 years in order to achieve
this goal. While progress has been made in some areas, more work needs
to be done. The centerpiece of the newest initiative is the BUilding
Infrastructure Leading to Diversity (BUILD) Program that is designed to
provide relatively under-resourced institutions with the opportunity to
provide a series of rigorous, mentored research experiences to their
students, many of whom are from backgrounds underrepresented in
biomedical research, with the goal of facilitating entry of a more
diverse pool of students into graduate programs for biomedical
research.
I want to emphasize that while all of these ambitious new
scientific endeavors provide unprecedented promise for advancing human
health, we cannot ignore the impact the sequester is having on
groundbreaking medical research. The fiscal year 2013 reduction of $1.6
billion, or 5.0 percent, is having a substantial impact on the
scientific community. If the Budget Control Act-imposed caps on
discretionary programs continue, and NIH funding is reduced
proportionally over the next 10 years, funding will decline by about
$19 billion. The consequences will be harmful to scientific progress
and to American leadership in science. NIH-funded investigators are
already feeling the effects as Institutes and Centers are forced to
fund a lower percentage of grant applications. In fiscal year 2012, we
funded 8,986 competing RPGs. In fiscal year 2013, our projection is
8,283. This trend is also reflected in our total research portfolio--we
expect to fund 34,902 RPGs this year compared to 36,259 in fiscal year
2012. With this new reality, more and more investigators will be unable
to pursue the bold ideas that NIH has traditionally supported.
NIH plays a significant role in the U.S. economy by advancing
scientific products and technologies that help maintain our Nation's
role as a global innovation leader.\11\ At a time when global
competition in the life sciences is intensifying, the American economy
cannot afford to lose ground in scientific efforts that promote human
health. Countries such as China and India are increasingly investing
resources into biomedical science and technology. According to the
Organization for Economic Cooperation and Development (OECD), in 2008,
including both public and private sources, the U.S. invested 2.8
percent of its GDP in research and development (R&D)--less than Israel,
Japan, Korea, Sweden, and Switzerland. Moreover, the U.S. ranks only
eighth in R&D as a share of GDP among countries in the OECD.\12\ China
has made policy changes to invest heavily in the life sciences
industry, moving them closer to becoming a world leader in science and
technology by the end of the decade.\13\ Over the past decade,
Singapore has also pursued a prominent role as a global leader in the
life sciences. For example, their pharmaceutical industry R&D funding
was five times greater than that of the U.S. in 2009, on a share of GDP
basis. Despite these factors, the United States is by far the largest
R&D performer globally, contributing $402 billion in 2009, accounting
for about 31 percent of the global total.\14\
But let me close on a more positive note. I began today by telling
you about some exciting new initiatives NIH is planning for fiscal year
2014. Now I want to tell you about our boldest new scientific
endeavor--one that we are all very excited about.
Neurological and psychiatric disorders such as Alzheimer's disease,
Parkinson's disease, autism, schizophrenia, and traumatic brain injury
inflict a tremendous toll on society, yet their underlying pathologies
remain unknown due to the great complexity of the human brain. This
complexity was once thought to be beyond the reach of scientific
understanding. Today, however, tremendous strides in neuroscience have
brought forward remarkable new opportunities for unlocking these
mysteries.
Indeed, neuroscience has made some extraordinary progress in recent
years. For example, a group of NIH-supported researchers has developed
a sophisticated neural interface that enables paralyzed people to move
a robotic arm, using just their thoughts. Using this robotic arm
system, 58-year-old Cathy Hutchinson recently was able to take a sip of
coffee on her own for the first time since she'd been paralyzed more
than 14 years earlier. A truly remarkable moment--but just a beginning,
because we need a lot more of these moments for a whole lot more
people.
In fiscal year 2014, NIH will begin its support of the Brain
Research through Advancing Innovative Neurotechnologies (BRAIN)
Initiative, in order to develop a deeper understanding of brain
function through the creation of new tools capable of examining the
activity of millions of nerve cells, networks, and pathways in real
time. By measuring activity at the scale of circuits and networks in
living organisms, we can begin to translate data into models that will
decode sensory experience, motor planning, and, potentially, even
memory, emotion, and thought. NIH is embracing a collaborative approach
in tackling this challenge, working with researchers from across the
country, industry, foundations, and other Government agencies including
the Defense Advanced Research Projects Agency and the National Science
Foundation. In fiscal year 2014, NIH will invest $40 million in this
initiative to leverage investment from a number of other sources,
including private sector and leading philanthropies. We believe that
successful completion of the BRAIN Initiative will revolutionize the
field of neuroscience and set the stage for major advances in diseases
such as Alzheimer's, Parkinson's, autism, schizophrenia, depression,
and epilepsy.
Granted, this is a very ambitious goal. But we at NIH have heard
and overcome such skepticism before. Take the example of the Human
Genome Project, which I had the privilege to lead. In its earliest
days, back in the late 1980s, many questioned the wisdom of that
proposal to sequence the 3 billion letters in the human genetic
blueprint. Nearly everyone in the research community agreed that it
would be fantastic to have a full readout of the human DNA instruction
book. But skeptics argued that it could not be done because the tools
and technologies didn't exist. In fact, they were right--we didn't have
the necessary technologies. But, the opportunity for dramatic progress
in genetics inspired a remarkable series of technical innovations.
These tools enabled the Human Genome Project to be successfully
completed in April 2003, ahead of schedule and under budget. Like the
Human Genome Project, we envision the BRAIN Initiative will create
data, tools, and technologies that will speed the efforts of many
different types of researchers all around the world. Though this
program will need to extend over many years, and we must be careful not
to overpromise immediate medical benefits, BRAIN will eventually lead
to scientific advances that will catalyze development of new treatments
and cures.
I have provided you today with a brief overview of NIH's past
successes and continuing commitment to basic and translational science,
as well as a glimpse into the critical role that NIH plays in our
domestic and global economies. We have never witnessed a time of
greater promise for advances in medicine than right now. With your
support, the future of medicine will be very bright.
This concludes my testimony, Mr. Chairman.
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\1\ http://cancergenome.nih.gov/PublishedContent/Files/pdfs/
1.1.0_CancerGenomics_TCGA-Genomics-Brochure-508.pdf.
\2\ http://www.nature.com/nature/journal/v489/n7417/pdf/
nature11404.pdf.
\3\ http://www.nature.com/nature/journal/v486/n7402/pdf/
nature11209.pdf.
\4\ http://www.sciencemag.org/content/339/6119/548.full.pdf.
\5\ http://onlinelibrary.wiley.com/doi/10.1002/stem.718/pdf.
\6\ http://www.sciencemag.org/content/326/5959/1501.full.pdf.
\7\ http://www.sciencemag.org/content/339/6121/819.full.pdf.
\8\ http://www.nia.nih.gov/alzheimers/topics/alzheimers-basics.
\9\ http://www.nejm.org/doi/pdf/10.1056/NEJMsa1204629.
\10\ http://www.plosone.org/article/
info%3Adoi%2F10.1371%2Fjournal.pone.0031302.
\11\ http://www.unitedformedicalresearch.com/wp-content/uploads/
2013/02/UMR_Impact_of_
Sequestration_2013.pdf.
\12\ http://www.itif.org/publications/winning-race-2012-memos-
science-and-technology.
\13\ http://www.itif.org/publications/leadership-decline-assessing-
us-international-
competitiveness-biomedical-research.
\14\ http://www.nsf.gov/statistics/seind12/c4/c4s8.htm.
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______
Prepared Statement of Anthony S. Fauci, M.D.
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of Allergy
and Infectious Diseases (NIAID) of the National Institutes of Health
(NIH). The fiscal year 2014 NIAID budget of $4,578,813,000 includes an
increase of $96,444,000 over the comparable fiscal year 2012 level of
$4,482,369,000.
NIAID conducts basic and clinical research with the ultimate goal
of improving human health through the development of diagnostics,
therapeutics, and vaccines for infectious diseases; and to increase our
understanding of the immune system, how it protects us from infection
and disease, and its role in immune-mediated diseases. NIAID also
addresses the scientific challenges that arise from emerging and re-
emerging infectious diseases, including influenza, HIV/AIDS,
tuberculosis, and malaria.
INFECTIOUS DISEASES RESEARCH
HIV/AIDS.--Through more than 30 years of supporting and conducting
basic and clinical research, NIAID has provided the scientific
foundation for groundbreaking interventions and strategies to treat and
prevent HIV/AIDS, including combination antiretroviral therapy (ART),
pre-exposure prophylaxis (PrEP), medical male circumcision, prevention
of mother-to-child transmission (PMTCT), microbicides, and
antiretroviral treatment as prevention. It is an exciting time in the
domestic and global fight against HIV/AIDS, and NIAID continues to
support research critical to a goal now within our reach: an AIDS-free
generation. The NIAID-funded HPTN-052 clinical trial--the ``Science''
magazine 2011 Breakthrough of the Year--conclusively demonstrated that
treatment of the HIV-infected person in a stable heterosexual
relationship with an uninfected partner dramatically reduces the
likelihood of transmitting HIV to the uninfected partner. Recently,
based upon results of the NIAID-funded iPrEx study and other research,
the Food and Drug Administration (FDA) approved the ART combination
drug Truvada as a prevention tool for uninfected adults at high risk
of acquiring HIV. Ongoing NIAID studies of PrEP, microbicides, and
PMTCT are exploring new strategies to limit HIV transmission in various
populations; one study (TLC-Plus) is evaluating the feasibility of a
community-level ``testing, link to care, and treatment'' strategy; and
the new population-based ART study (PopART) will determine the effects
of universal testing and immediate ART on HIV transmission.
NIAID continues its longstanding efforts to develop an effective
HIV vaccine. NIAID is currently investigating the reasons for the
modest efficacy (31 percent protection) of the HIV vaccine candidates
used in the RV-144 clinical trial conducted in Thailand several years
ago, and will seek to achieve significantly better results with future
vaccine candidates. In this regard, NIAID has funded two new HIV
vaccine initiatives and also is moving into Phase I clinical trials to
determine if passively transferred neutralizing antibodies can protect
against HIV infection.
Tuberculosis and Malaria.--Drug-resistant forms of tuberculosis
(TB) are emerging worldwide, and co-infection with TB and HIV is a
major cause of morbidity and mortality in the developing world. NIAID
is helping to bring TB research into the 21st century by applying
microbial genomic sequencing technologies, investing in the basic
science underlying point-of-care diagnostics, supporting research to
develop vaccine candidates, and engaging in public-private partnerships
for drug development. These efforts are bearing fruit: NIAID
researchers showed the potential of linezolid (originally developed for
staphyloccocal infections) as a treatment for extensively drug-
resistant TB, and FDA recently approved the first new TB drug
(bedaquiline) in decades.
NIAID continues its work to combat malaria. To counter the emerging
resistance to artemesinin, a first-line malaria drug, NIAID scientists
have identified a region in the genome of the parasite linked to
artemesinin resistance. NIAID is pursuing its promising efforts to
develop candidate malaria vaccines, including studies conducted at the
NIH Clinical Center.
Other Infectious Diseases of Domestic and Global Health
Importance.--Events in the news remind us almost on a daily basis of
the global threat of emerging and re-emerging infectious diseases.
Paramount among these are seasonal influenza and potential pandemic
influenza threats, such as the H7N9 influenza emerging in China. NIAID
conducts research on the pathogenesis and transmissibility of
influenza, and the emergence of epidemics and pandemics, with the goal
of furthering the development of influenza diagnostics, therapeutics,
and vaccines. We have made significant strides toward developing a
universal influenza vaccine, which would obviate the need for annual
influenza vaccination and enhance our ability to respond to the
emergence of influenza pandemics. Though it will be years before this
goal is achieved, NIAID grantees and scientists, including those at
NIAID's Vaccine Research Center, have demonstrated success in animal
models, and have begun Phase I trials in humans. In addition, the NIAID
Human Immunology Project Consortium is characterizing human immune
responses to improve vaccines and immunotherapeutics for a variety of
infectious diseases, including influenza.
NIAID scientists have developed an animal model to study the novel
coronavirus recently identified in Saudi Arabia, and to evaluate
potential treatments and vaccines. They have shown recently that a
combination of two antiviral drugs, ribavirin and interferon, can
inhibit replication of the virus in cell culture.
Common microbial infections are increasingly becoming resistant to
the drugs generally used to treat them. Methicillin-resistant
``Staphyloccus aureus'' (MRSA) has been a longstanding problem. Of
particular concern is the recent emergence of other antibiotic-
resistant organisms such as the carbapenem-resistant Enterobacteriaceae
(CRE) including ``Klebsiella pneumoniae''. To address the challenge of
antimicrobial resistance, NIAID continues its efforts in the
development and testing of vaccines to prevent these infections, and in
the evaluation of new and repurposed drugs to treat antimicrobial-
resistant organisms. This year, NIAID will establish a leadership group
for a national network to conduct clinical research on antibacterial
resistance.
We are witnessing rapid changes in the treatment of hepatitis C
virus (HCV), a major cause of chronic liver disease and a common co-
infection with HIV. Promising new HCV protease inhibitor drugs recently
approved by FDA were developed with the help of NIAID and other NIH
Institutes. NIAID also is collaborating with industry to develop new
HCV therapeutics and vaccines, and to test approved drugs in
individuals with HCV/HIV co-infection.
NIAID biodefense research continues to build on our fundamental
understanding of the biology of and immune response to microbes. Recent
successes include FDA approval of a monoclonal antibody to treat
anthrax and progress on vaccines against Ebola and other hemorrhagic
fever viruses. NIAID biodefense research also addresses the global
threat of emerging and re-emerging diseases, including the development
of vaccines for dengue fever and animal models to study West Nile
virus.
RESEARCH ON IMMUNOLOGY AND IMMUNE-MEDIATED DISORDERS
NIAID remains committed to basic and clinical research on the
immune system and immune-mediated diseases, including the development
and testing of adjuvants to enhance the immune response to vaccination.
NIAID also supports groundbreaking studies in the treatment of food
allergy, a significant concern for many Americans. Recently, NIAID-
funded scientists found that oral egg immunotherapy can reduce and even
eliminate allergic responses for extended periods in certain children.
Similarly promising results showed that peanut immunotherapy given
under the tongue can reduce the allergic response in adolescents and
adults.
CONCLUSION
NIAID conducts critical research on infectious and immune-mediated
diseases that ultimately will enable interventions to improve health
domestically and worldwide. Understanding and developing
countermeasures against microbes that threaten our public health is
central to NIAID's mission. NIAID will continue to fund meritorious
basic and clinical research with the ultimate goal of translating these
discoveries into global public health benefits.
______
Prepared Statement of Gary H. Gibbons, M.D.
Mr. Chairman and distinguished members of the subcommittee: I am
pleased to present the President's budget request for the National
Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of
Health (NIH). The fiscal year 2014 budget of $3,098,508,000 includes an
increase of $25,206,000 over the comparable fiscal year 2012 level of
$3,073,302,000.
NHLBI leads research and education programs to discover and apply
knowledge to improve health by preventing and treating heart, lung, and
blood diseases. It is a privilege to serve as NHLBI Director in this
time of unprecedented opportunity in biomedical research. Today, I will
discuss new opportunities to reduce health disparities, advance
understanding of complex chronic diseases, and enhance clinical
research.
HEALTH DISPARITIES RESEARCH
The NHLBI portfolio includes studies of many diseases that impose
strikingly disparate burdens on Americans from different walks of life.
Understanding and alleviating health disparities has been a passion of
mine throughout my career, and I am honored to lead an Institute with
such a longstanding commitment to supporting work in that area. Many of
you are familiar with the NHLBI's large epidemiological studies that
focus on minority populations, including the Jackson Heart Study in
African Americans, the Hispanic Community Health Study, the Multi-
Ethnic Study of Atherosclerosis, which includes a sizeable cohort of
Asian Americans, and the Strong Heart study in American Indians. Our
recent investments in genotyping of diverse cohorts promise to shed
critical light on biological differences in disease susceptibility as
well as the interactions between genes and environment as determinants
of health among all Americans. We also have an outstanding record of
including substantial numbers of minorities in our clinical research,
particularly in studies of high blood pressure, which appears with
great frequency and often devastating complications in African
Americans.
Efforts to date have yielded progress that has benefited most
people to some extent but, unfortunately, has done little to close the
gaps that persist between the healthiest and least healthy segments of
society. Because health disparities are complex and are clearly
influenced not only by genetics but also by factors such as family,
social community, and physical environment, we believe that they offer
an excellent model for a new ``systems'' approach to our research
strategy. Until recently scientists have had to consider such factors
separately; for instance, one researcher might look at basic biological
pathways or genetic factors, while another examines lifestyle choices
and a third considers socioeconomic influences. This piecemeal approach
provides a limited view of how disease occurs and, more important, how
it can be prevented or managed effectively. To revolutionize our
understanding of health and disease, we are now developing and
exploiting new tools that enable consideration of many factors--
biological, behavioral, environmental--together in a holistic way.
That, I believe, is the path to future progress in preventing and pre-
empting chronic heart, lung, and blood disorders. If we can develop the
``systems'' research model for health disparities research we can
transform both science and medicine by applying it more broadly to
other public health needs.
A NEW PARADIGM FOR UNDERSTANDING COMPLEX DISEASES
Let me give you one example of recent findings that highlight the
value of a cross-disciplinary approach. We have known for decades that
the foods we eat influence our risk of developing cardiovascular
disease (CVD). Observational studies have taught us the value of so-
called heart-healthy diets that emphasize fruits, vegetables, whole
grains, fish, and ``good'' fats such as olive oil. Nevertheless,
controversies persist about the potential harmful effects of red meat
consumption. Scientists still don't know why certain foods increase or
reduce the risk of CVD.
Recently, a provocative series of NHLBI-funded studies provided
some important new insights into the potential link between red meat
consumption and atherosclerotic CVD. Researchers have shown that the
bacteria that reside in our guts and metabolize L-carnitine, a
substance found in red meat, may be an important culprit behind CVD.
This interaction between diet and gut microbes leads to the production
of TMAO (trimethylamine-N-oxide), an organic compound that circulates
in the blood and promotes the ``clogging of arteries'' by inhibiting
the removal of cholesterol from atherosclerotic plaque.
This and other work is dramatically enhancing our view of how the
trillions of microbes that co-exist in and around our bodies contribute
to both health and disease. The research perfectly illustrates a
``systems'' approach that interactively integrates studies in mice as
well as large-scale population science and smaller-scale human studies.
It provides an entirely new and critical understanding of the dynamic
interplay between the factors that predispose patients to CVD.
ENHANCING CLINICAL RESEARCH
As we work to integrate our research efforts across multiple
disciplines, we are placing particular emphasis on ensuring that our
clinical research is robust. A major challenge is to enhance clinical
trials, which provide critical evaluation of new preventive and
therapeutic approaches but are, arguably, some of our most challenging
and expensive undertakings. In recent years, the NHLBI has been
exploring ways to make trials more efficient and more applicable to
real-world clinical settings. Moving forward, we plan to build on past
successes while capitalizing on new technologies and data sources, such
as electronic medical records.
For many years, the NHLBI has used a network model to increase the
efficiency of clinical trials. Our networks have a strong track record
of conducting multiple, multi-center, clinical trials using
standardized operations and sustainable infrastructures that minimize
the time required to start new studies. They span a wide range of
topics, such as asthma, cardiovascular cell therapy, pediatric heart
disease, heart failure, childhood obesity, and transfusion medicine. A
major problem facing our healthcare system is the costly cycle of
chronic disease care that is characterized by persistent debilitating
symptoms, hospitalizations for acute exacerbations of the condition,
eventual hospital discharge, and then subsequent re-hospitalizations.
To address this clinical practice challenge, the NHLBI is supporting
innovation in discovery science that holds promise for breaking this
vicious cycle of chronic heart, lung, and blood disorders. In 2014, we
will pilot a new network structure to evaluate treatment strategies for
acute, serious lung conditions--such as exacerbations of chronic
obstructive pulmonary disease--that require hospitalization. If the new
model proves successful we will apply it to clinical trials of other
chronic diseases that are treated in inpatient clinical settings.
Another cost-effective strategy that the NHLBI has used very
successfully is funding ancillary studies piggybacked onto trials to
maximize return on investment. For example an NHLBI-funded clinical
trial demonstrating that aspirin reduces the risk of heart attack also
included ancillary studies that sought to identify new risk factors for
CVD. These ancillary discovery science projects superimposed on the
original clinical trial yielded strong evidence that elevated levels of
a marker for inflammation called c-reactive protein are correlated with
CVD events. The insights gained from the original clinical trial and
subsequent ancillary studies have led to an innovative strategy to
reduce CVD that targets the inflammatory process as a causative factor
in heart attacks. Accordingly, the NHLBI recently funded the
Cardiovascular Inflammation Reduction Trial to determine whether
treatment with the anti-inflammation drug methotrexate, which is
commonly prescribed for rheumatoid arthritis, reduces the risk of heart
attacks and strokes. Taken together, these studies illustrate the
NHLBI's ongoing efforts to enhance the efficiency and return-on-
investment of our clinical trial portfolio so that advances in the
practice of medicine are translated into healthier lives for all
Americans.
We also are pursuing new opportunities to conduct trials that are
bigger, but simpler, with clinically relevant end points that leverage
routine medical care and existing data in electronic medical records
and registries. By using electronic health records data from real-world
clinical practice, we hope not only to make trials more relevant to
clinical practice, but also to make the results more robust and
reproducible by including hundreds of thousands of participants. In
fiscal year 2014, the Institute will explore the use of electronic
medical records in clinical trials through a new initiative to compare
the ability of two data sources, electronic health records and
traditional prospective patient-based clinical and research data, to
answer research questions about pediatric pulmonary vascular diseases.
We anticipate that these innovations that enhance the cost-
effectiveness of NHLBI's approach to supporting clinical research will
yield additional new discoveries that have a dramatic impact on the
health outcomes of patients with chronic heart, lung, and blood
disorders.
______
Prepared Statement of Richard J. Hodes, M.D.
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute on Aging
(NIA) of the National Institutes of Health (NIH). The fiscal year 2014
budget includes $1,193,370,000, which is $72,979,000 more than the
comparable fiscal year 2012 level of $1,120,391,000.
More than 40 million people age 65 and older live in the United
States, and data from the Federal Interagency Forum on Aging-Related
Statistics indicate that their numbers will double by 2040. In less
than 50 years, the number of ``oldest old''--people ages 85 and older--
may quadruple. As record numbers of Americans reach older age, profound
changes will occur in our health care and social systems.
NIA leads the national effort to understand aging and to identify
and develop interventions that will help older adults enjoy robust
health and independence, remain physically active, and continue to make
positive contributions to their families and communities. We support
genetic, biological, clinical, behavioral, and social research related
to the aging process, healthy aging, and diseases and conditions that
often increase with age. We also carry out the crucial task of training
the next generation of researchers who specialize in the issues of
aging and old age. Finally, we support a vibrant program of basic,
clinical, and translational research through our Intramural Research
Program, which underwent a revision in 2013, to recognize new paradigms
in the field of aging research and integrate laboratories and resources
in a way that will more efficiently foster discovery.
IMPROVING THE HEALTH AND WELL-BEING OF OLDER AMERICANS
Life expectancy in the developed world has improved dramatically
over the last century, and advances in public health and medicine are
allowing people to stay healthier longer. But, since 1980, U.S. life
expectancy, especially for women, has lagged behind other wealthy
nations, and cross-national studies suggest that older Americans get
sicker sooner than older Europeans. Similar disparities in health and
longevity exist across geographical areas within the United States. NIA
has established an initiative to identify and address the behaviors and
social circumstances behind these differences.
NIA-supported investigators are continuing to work to identify the
optimal means to address the unique health needs of older individuals.
For example, studies have shown that regular physical activity can
improve physical performance in older people, and with the U.S. Surgeon
General, NIA has launched its nationwide ``Go4Life'' campaign to
motivate older Americans to engage in physical activity and exercise.
However, definitive evidence that physical activity can prevent
mobility disability is lacking, and NIA supports the Lifestyle
Interventions and Independence for Elders Study to assess whether a
specific physical activity program can prevent disability in sedentary
older individuals.
NIA-supported investigators are also testing interventions for
health conditions common to old age. For example, the Centers for
Disease Control and Prevention reports that fully half of older
Americans have at least two chronic health conditions that compromise
quality of life. NIA participates in a trans-NIH initiative to develop
interventions to modify behavior and improve health outcomes among
individuals with multiple chronic conditions. In addition, NIA supports
research on rehabilitation from a number of acute and chronic
conditions, including the development and pilot testing of a smart
phone-based self-management system for older patients with heart
failure and development of a unique biomaterial that can act as a
temporary replacement for both bone and cartilage. Other ongoing
studies include the ASPirin in Reducing Events in the Elderly (ASPREE)
trial to determine whether the benefits of aspirin outweigh the risks
in people over 70; testosterone supplementation to delay or prevent
frailty in older men; exercise for mood, health, and cognition; and
several interventions for menopausal symptoms.
THE FIGHT AGAINST ALZHEIMER'S DISEASE
It is estimated that as many as 5 million people in the United
States aged 65 and older currently have Alzheimer's disease (AD), and
annual costs of care for dementia, of which Alzheimer's is the most
common cause, have been calculated using data from the Health and
Retirement Study at between $157 billion and $215 billion among people
70 and older. Unless effective treatment or preventive interventions
are identified, these numbers will rise significantly as the number of
older Americans continues to increase. NIA has been a leader in the
implementation of the National Alzheimer's Project Act and the
development of the National Plan to Address Alzheimer's Disease. Recent
initiatives have boosted support for AD research, including the NIH
Director's allocation of an additional $50 million in fiscal year 2012
and $40 million in fiscal year 2013 for the disease. In the fiscal year
2014 President's budget request for NIA, $80 million of the increase
planned for competing research project grants will be devoted to
Alzheimer's disease projects, in response to recommendations of the
Alzheimer's Disease Research Summit held in May 2012. The recent launch
of the International Alzheimer's Disease Research Portfolio (IADRP), a
publicly available database to capture the full spectrum of current AD
research investments and resources throughout the world, will
facilitate coordination of these efforts.
One active and highly promising area of research is the
identification and elucidation of risk and protective genes for AD. For
example, a variation in TREM2, a gene involved in inflammation and
immune response, was recently identified as a moderate risk factor for
late-onset AD, and a variant of the BCHE gene has been associated with
deposition of beta-amyloid in the brain--a pathologic hallmark of the
disease. Other investigators found that in mice, ApoE-4, the best-known
genetic risk factor for late-onset AD, is associated inflammation of
the blood vessels that feed the brain involving a molecule called
cyclophilin A, suggesting that cyclophilin A may be a viable drug
target. Finally, investigators with the NIH-supported AD Genetics
Consortium have identified a gene, ABCA7, which appears to be more
strongly associated with AD in African Americans than in individuals of
European ancestry. Further study is needed to confirm and extend this
finding.
NIH currently supports more than 35 clinical trials, including both
pilot and large-scale trials, of a wide range of interventions to
prevent, slow, or treat AD and/or cognitive decline; more than 40
compounds are in preclinical development through the AD Translational
Initiative. Funding for the groundbreaking Alzheimer's Disease
Cooperative Study was renewed earlier this year, and several
interventional studies are planned: a secondary prevention trial to
test an amyloid-clearing drug in 1,000 symptom-free older volunteers
with abnormal levels of brain amyloid accumulation; a randomized,
controlled trial to find out if supervised aerobic exercise can
influence cognitive decline, slow brain atrophy, or mitigate
Alzheimer's pathology in older adults with mild cognitive impairment, a
condition that often leads to AD; and a study to test the drug prazosin
to help control agitation, a common symptom in AD patients.
UNDERSTANDING AGING AT THE MOST BASIC LEVEL
NIA initiatives on the molecular mechanisms of aging, from in-depth
study of single cells to the broad study of organisms at the systems
level, continue to advance our understanding of the basic underpinnings
of the aging process. The NIH Geroscience Interest Group (GSIG) was
formed in 2012 to accelerate and coordinate efforts to promote
discovery on the common risks and mechanisms behind age-related
diseases and conditions. The GSIG has planned a number of initiatives
for coming years, including informational activities, expansion of
current initiatives to incorporate aging-related aims, and new trans-
NIH funding initiatives. A GSIG workshop on inflammation and age-
related diseases was held in September 2012, and a larger-scale
workshop tentatively entitled ``Geroscience: Foundations for Delaying
Chronic Disease and Increasing Healthspan'' is planned for fall 2013.
EMPOWERING THE NEXT GENERATION OF AGING RESEARCHERS
The need for health care professionals and research scientists who
specialize in the unique needs of older individuals is becoming ever
more urgent. Recently, NIA established the Grants for Early Medical/
Surgical Subspecialists' Transition to Aging Research (GEMSSTAR)
program to support physicians who seek to become clinician-scientists
in geriatric aspects of their subspecialty. NIA has also established a
program targeting undergraduate students from diverse backgrounds in
order to advance their interest in and knowledge of aging issues.
______
Prepared Statement of Story C. Landis, Ph.D.
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of
Neurological Disorders and Stroke (NINDS) of the National Institutes of
Health (NIH). The fiscal year 2014 NINDS budget of $1,642,619,000
includes an increase of $19,275,000 over the comparable fiscal year
2012 level of $1,623,344,000.
COMBATING NEUROLOGICAL DISORDERS
The NINDS mission is to reduce the burden of neurological disorders
through research. For stroke, research on prevention and treatment led
to reductions of the age-adjusted death rate by 36.9 percent and of the
actual number of deaths by 22.9 percent from 1999 to 2009.\1\
An intensive and inclusive NINDS planning process has identified
the highest priority research investments to continue this progress
against stroke. Experts across disciplines agreed that stroke clinical
trials networks could accelerate progress. In response, NINDS is
establishing a flexible stroke clinical trials network to conduct
prevention, treatment, and recovery trials. With shared infrastructure,
the network will better set priorities for studies, reduce cost and
time in start-up, and therefore significantly improve efficiency. The
network builds on lessons from the NeuroNEXT network, which expedites
early phase clinical trials of new treatments, especially for rare
diseases. NeuroNEXT uses a single Institutional Review Board and
standard site contracts, which reduce time required to start a trial by
months. It also accommodates projects from academic investigators or
private partners. Trials for spinal muscular atrophy (SMA) biomarkers
and secondary progressive multiple sclerosis are under way, and
planning has begun for clinical trials of two therapies developed by
the NIH Therapeutics for Rare and Neglected Disease Program.
Reducing cognitive impairment from brain vascular disease is
another priority that emerged from planning. Stroke itself is a major
cause of dementia. Furthermore, the 7 million U.S. stroke survivors
have an increased likelihood of cognitive problems, and the 13 million
people with ``silent strokes'' \2\ may also be at risk. Vascular risk
factors are also associated with Alzheimer's disease. In fact, there is
a spectrum from pure vascular dementia to pure Alzheimer's disease,
with most patients having contributions from both.\3\ This month a
scientific workshop on Alzheimer's Related Dementias, part of the
National Alzheimer's Project Act activities, focused on vascular
dementia.
Traumatic Brain Injury (TBI) is the leading cause of death and
disability in children and young adults, common among the elderly, and
a major concern for the military and veterans. New studies will address
two reasons why more than 30 major clinical trials of interventions for
TBI failed to demonstrate improved outcomes: classification schemes do
not distinguish between different types of damage in different parts of
brain that may respond differently to interventions, and large
variations in outcomes among medical centers confound assessment of
interventions in clinical trials. A study of 1,000 children will
evaluate the effectiveness of six major critical care guidelines for
severe, pediatric TBI that lack compelling evidence. Another
prospective, observational, multi-center study of 5,000 adults and
children with TBI will be coordinated with studies by the European
Union and the Canadian Institute of Health Research to enhance the
statistical power to detect differences. The research community has
agreed upon standards through the NINDS TBI Common Data Elements
program that will allow meaningful comparison across studies, and the
Department of Defense and NIH-led Federal Interagency TBI Research
informatics system (FITBIR) provides a database for sharing
information. NIH is also addressing TBI through the Foundation for
NIH's Sports and Health Research Program, with support from the
National Football League. In December a workshop focused on Chronic
Traumatic Encephalopathy (CTE), a neurodegenerative disorder that can
follow repetitive mild brain trauma in sports and the military. Follow-
up research solicitations are underway, and this public private
partnership will address other key aspects of sports and health in the
coming years.
Epilepsy is another common disorder that affects people of all
ages. Every 6 years since 2001, the Epilepsy Benchmarks process has
brought NINDS, the research community, and non-governmental
organizations together to establish research milestones and monitor
progress. This April NINDS convened a major workshop to assess progress
and set pathways forward. Previous Benchmarks guided investments that
are now yielding important gene findings, advances in understanding how
epilepsy develops, and attention to comorbidities, including Sudden
Unexplained Death in Epilepsy (SUDEP). Future Benchmarks will focus on
disease progression and modification, predictability of seizures and
treatment response, and aspects of gender, ethnicity, and age (children
and elderly), among other issues. Opportunities from other investments
could also have a significant impact on epilepsy. The community is
excited, for example, about advances in genetics, ``big data,'' and
brain circuit analysis.
Opportunities are also emerging for many other brain diseases,
common and rare. Induced pluripotent stem cells derived from patients
with Parkinson's disease, amyotrophic lateral sclerosis (ALS),
Huntington's and other disorders allow laboratory testing of potential
drugs. Biomarkers under development for Parkinson's, SMA, and other
diseases will speed clinical testing. Brain stimulation therapies have
proven benefit for Parkinson's disease, essential tremor, and dystonia,
and show promise for diseases including epilepsy and Tourette syndrome.
In research settings, brain machine interfaces enable paralyzed
individuals to control a robotic arm and hand; development of practical
devices is underway. Gene discoveries have led to mechanism targeted
therapies that are now in the translational pipeline for many diseases,
for example, muscular dystrophies, SMA, familial dysautonomia, and
fragile X.
BASIC NEUROSCIENCE
Researchers in academia and industry agree that basic science
drives progress against disease. A few recent examples: genes
discovered for epilepsy, ALS, and autism enable the dissection of
underlying disease mechanisms, pointing to potential targets for
therapy development. Research is also revealing unexpected ways that
degeneration propagates in the brain, why acute pain can become
chronic, and that serious disabilities in children born prematurely may
be more reversible than expected. Science of the normal brain advanced
this year on topics as diverse as the mechanisms of itch, how the brain
clears waste, control of brain blood flow in infants, the influence of
anesthetics on consciousness, and brain circuits for memory.
NINDS relies on investigator-initiated research throughout its
programs. Engaging the insight and ingenuity of the scientific
community in this way is especially crucial for basic research. The
Institute has also emphasized the importance of transparent reporting
of research findings, stressing rigor and reproducibility. A June 2012
NINDS workshop brought together representatives of all major
stakeholders, which has already lead to changes within and outside the
NIH, including policies of leading journals.\4\
Technology can also empower investigators. Investment by the NIH
and others, together with advances in optics, computer science, genetic
engineering, and other disciplines, has led to promising technological
strategies to study the activity of large numbers of brain cells and
the intricacies of their connections. The Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative partners
Federal agencies and private foundations in a coordinated program to
develop and apply these emerging opportunities, including study of the
human brain. This will ultimately revolutionize understanding of how
networks of brain cells enable us to perceive, think, and act, and what
goes wrong in diseases of the brain. A stellar committee of scientists
will guide this initiative, with recommendations on first steps due
this fall and a more complete plan the following summer. History
suggests that the most important benefits of BRAIN will be those that
we have not yet even imagined.
---------------------------------------------------------------------------
\1\ ``Circulation'' 134:e6-245, 2013.
\2\ ``Circulation'' 125:e2-e220, 2012.
\3\ ``Neurology'' 72:368-74, 2009.
\4\ e.g., ``Nature'' 490:187-91, 2012; ``Nature'' 496:398, 2013;
``Nature Neuroscience'' 16:1, 2013; 16:517, 2013.
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______
Prepared Statement of Harold E. Varmus, M.D.
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Cancer Institute (NCI)
of the National Institutes of Health (NIH). The fiscal year 2014 NCI
budget of $5,125,951,000 includes an increase of $63,189,000 over the
comparable fiscal year 2012 level of $5,062,762,000.
CANCER DEATHS CONTINUE TO DECLINE
The 2013 Report to the Nation on the Status of Cancer shows that
overall cancer death rates continued to decline in the United States
among both men and women, among all major racial and ethnic groups, and
for all of the most common cancer sites, including lung, colon and
rectum, female breast, and prostate. However, death rates continued to
increase for melanoma of the skin (among men) and for cancers of the
liver, pancreas, and uterus. The Report also emphasizes the importance
of human papilloma virus (HPV) infection as a cause of the growing
number of cancers, and shows that incidence rates are increasing for
HPV-associated oropharyngeal and anal cancers. Also noted was that HPV
vaccination coverage remains disappointingly low, falling short of the
U.S. Government's Healthy People 2020 target, and much lower than
vaccination rates reported in several other countries.
The continued decline in death rates for most cancers shows that
our nation's investment in cancer research produces life-saving
approaches to cancer control. However, there is still critical work to
do, for example, in reducing tobacco exposure and obesity. Taken
together, adverse health effects from cigarette smoking--including
heart disease, stroke, and cancer--account for an estimated 443,000
deaths every year in the U.S.; nearly 1 in 5 deaths that could have
been prevented. Since tobacco is responsible for about 30 percent of
all cancer deaths in the U.S. (approximately 174,000 preventable cancer
deaths in 2013), NCI continues to support research into methods to
encourage smoking cessation and to discourage initiation; behavioral
modification; and effectiveness of tobacco control efforts. Obesity,
another significant cause of disease and preventable death, is
associated with heart disease, stroke, type 2 diabetes and at least
eight types of cancers. NCI funds research on the molecular mechanisms
of obesity and cancer, and has developed new initiatives that explore
ways to prevent and control obesity as a cancer risk factor.
NATIONAL CANCER INSTITUTE-SUPPORTED RESEARCH ADVANCES
The past year has yielded significant advances across the spectrum
of cancer research, including studies of cancer mechanisms, prevention,
detection, and therapy. One cancer detection study showed that the
protein fibulin-3 may be able to identify patients with mesothelioma,
suggesting that it may be a promising biomarker for high-risk
populations exposed to asbestos. Another study found a way to target
mesothelin, a cell surface protein that is present in normal tissues
but overexpressed in more than 90 percent of pancreatic cancers and
mesotheliomas, as well as in lung and ovarian cancers. Currently, the
NCI intramural program is conducting a Phase I study of SS1P, an
immunotoxin that targets mesothelin and destroys cancer cells, with
plans for a Phase II study under way.
NCI is supporting research to identify the genetic drivers of
cancer, and to advance adoption of precise tumor diagnosis and the
development of targeted therapies. The two major genomics initiatives,
involving hundreds of investigators nation-wide, are The Cancer Genome
Atlas (TCGA) and the Therapeutically Applicable Research to Generate
Effective Treatments (TARGET) initiative, focused on adult and
pediatric cancers respectively. TCGA recently completed a study of lung
squamous cell carcinoma that identified several potential therapeutic
targets related to the initiation and progression of that disease.
Another study examined nearly 400 endometrial (uterine) cancers and
identified four new subtypes with several possible therapeutic targets.
This study also found genomic similarities between endometrial and
other cancers, including breast, ovarian, and colorectal. A TARGET
study identified a subclass of acute lymphoblastic leukemia with high
risk of recurrence associated with novel chromosomal translocations;
these translocations represent exploitable therapeutic targets. Another
TARGET study found few recurrent mutations among 240 cases of high-risk
neuroblastoma, suggesting a limited number of targets for this
pediatric disease.
In 2011, one of several noteworthy achievements was FDA approval of
a new class of drug, vemurafenib, for the treatment of metastatic
melanoma. The drug targets mutant forms of the BRAF protein, which is
mutated in about 60 percent of these patients, leading to inhibition of
a key growth pathway in the tumor cell, the MAPK pathway. Although the
drug can increase the lifespan of these patients, almost all patients
eventually develop drug resistance and relapse. Recent observations
from several research groups have indicated that drug resistance can
arise by any of several mechanisms. Some resistance is attributable to
activation of the MAPK pathway, which can result from further mutation
of BRAF itself or changes in other genes in the MAPK pathway. In other
cases, resistance seems to result from activation of parallel pathways.
These findings are now leading to clinical trials testing the
hypothesis that combining the BRAF inhibitor with drugs that have been
shown in preclinical models to reduce development of these resistance
mechanisms will lead to longer therapeutic responses.
A potentially exciting therapeutic advance has come from
immunotherapy research for B cell lymphoma being conducted at several
institutions. The approach is to use genetic engineering to construct a
chimeric antigen receptor (CAR) by combining parts from two different
receptors, each with key immune functions, into one receptor that is
then expressed by the patient's own normal T cells. Early-phase
clinical trials with a receptor called anti-CD19 CAR, which works by
directing T cells to the malignant B cells of the tumor, have resulted
in several dramatic long-term responses in patients with advanced stage
lymphoma.
PRECISION MEDICINE--APPROACHES TO CANCER
Incorporation of genomics into cancer research and clinical trials
constitutes a growing portion of the Institute's research portfolio. In
the years ahead, NCI and the entire cancer research enterprise will
extend studies of the pathogenetic roles for specific genomic changes
in tumors and test more interventions that are based on genetic
profiles of tumors. There are several ways in which NCI is expanding
its pursuit of these goals, most notably by mandating that all NCI-
sponsored clinical trials include tissue collection and genomic
analysis. NCI is also developing new approaches that explore the
relationship between a cancer patient's genomic data (genotype) and the
behavior of each patient's tumor (phenotype). One such study is the
Exceptional Responders initiative, which will begin with phenotypes--
asking why a small number of patients respond very well to a particular
regimen, while the same treatment fails in almost all others with the
same cancer type. To probe this phenomenon, researchers will explore
the genomic data (genotype) to look for clues as to why some patients
enrolled in clinical trials respond to agents that do not benefit most
patients in the same study. Some recently reported cases provide
dramatic evidence for how a combination of molecular factors can
explain why patients responded so well to therapy while comparable
patients did not.
An approach from the opposite perspective (genotype to phenotype)
is the ``NCI MATCH'' study, which aims to screen about 3,000 patients
with advanced cancers in an effort to find approximately 1,000 such
cancers with genetic mutations for which new therapies, including some
not yet approved for use, are made available by the pharmaceutical
industry through collaborative arrangements. This approach will provide
a level of genomic data far beyond what would typically be available
when genotyping is limited to one or more mutations known to be
associated with a particular cancer type. There is a great opportunity
for investigator-initiated research to build on information that
emerges from this kind of novel trial, leading to yet greater
therapeutic insight.
TARGETING RAS
The Frederick National Laboratory for Cancer Research (FNLCR) is a
federally Funded Research and Development Center (FFRDC) supported by
NCI, providing a national resource with unique capabilities for the
development of new technologies and the translation of basic science
discoveries into novel agents for the prevention, diagnosis and
treatment of cancer and AIDS. NCI is poised to launch a large-scale
project targeting RAS, an oncogene known for decades to drive the
development of many types of cancers and about a quarter of all cancers
in the U.S., including more than 90 percent of pancreatic
adenocarcinomas. However, despite that information, the cancer research
community has failed to develop effective treatments. Now, with the
knowledge of new chemical approaches to inhibit the RAS protein
directly and a deeper understanding of how RAS signaling works, NCI is
launching a large-scale project to develop therapeutic strategies
against cancers driven by RAS through a national ``hub and spoke''
model with scientific leaders, core facilities and important
technologies at the FNLCR hub, and research led by investigators at
companies, academic institutions and the NCI intramural research
program at the spokes.
We find ourselves at a time of tremendous opportunity in cancer
research, building our knowledge of the genetic changes that cause
cancer, and finding new ways to use this information to diagnose, treat
and even prevent cancers. The President's budget for 2014 for the
National Cancer Institute will support studies intended to foster the
discoveries essential for this next frontier of cancer research.
______
Prepared Statement of Thomas R. Insel, M.D., Director, National
Institute of Mental Health
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of Mental
Health (NIMH) of the National Institutes of Health (NIH). The fiscal
year 2014 NIMH budget of $1,465,782,000 represents a decrease of
$11,734,000 below the comparable fiscal year 2012 level of
$1,477,516,000. In my statement, I will review the scope of mental
disorders in the United States and their impact on public health, and I
will outline examples of NIMH's research efforts designed to address
this challenge.
PUBLIC HEALTH BURDEN OF MENTAL ILLNESS
The National Institute of Mental Health (NIMH) is the lead Federal
agency for research on mental and behavioral disorders, with a mission
to transform the understanding and treatment of mental illnesses
through basic and clinical research. The global burden of mental
illness is enormous. An estimated 11 million American adults
(approximately 5 percent of all adults) suffer from a seriously
disabling mental illness each year.\1\ Mental disorders are the leading
cause of disability in the United States and Canada, accounting for 28
percent of all years of life lost to disability and premature mortality
(Disability Adjusted Life Years or DALYs) for people age 15-49.\2\ The
personal, social, and economic costs associated with these disorders
are tremendous. A cautious estimate places the direct and indirect
financial costs associated with mental illness in the U.S. at well over
$300 billion annually, and it ranks as the third most costly medical
condition in terms of overall healthcare expenditure, behind only heart
conditions and traumatic injury.\3\ \4\ Even more concerning, the
burden of illness for mental disorders is projected to sharply increase
over the next 20 years.\5\
NIMH-supported research has found that Americans with serious
mental illness (SMI)--in which the ability to function in daily life is
significantly impaired--die 8 years earlier than the general
population.\6\ People with SMI experience chronic medical conditions
and the risk factors that contribute to them more frequently and at
earlier ages. There are low rates of prevention, detection, and
intervention for chronic medical conditions and their risk factors
among people with SMI, and this contributes to significant illness and
earlier death.
PREDICTING AND PREVENTING PSYCHOSIS
In the past, we viewed mental disorders as chronic conditions
defined by their apparent symptoms, even though behavioral
manifestations of illness are in fact the last indications--following a
cascade of subtle brain changes--that something is wrong. We understand
now that mental disorders are brain disorders, with specific symptoms
rooted in abnormal patterns of brain activity. Moving forward, NIMH
aims to support research on earlier diagnosis and quicker delivery of
appropriate treatment, be it behavioral or pharmacological.
The majority of people with serious mental illness (SMI)--in which
the ability to function in daily life is significantly impaired--
experience significant delays to seeking care--nearly 2 years, on
average.\7\ \8\ Untreated SMI, particularly psychosis, poses an
increased risk for using potentially life-threatening, self-
administered treatments, such as legal or illicit substances,
potentially resulting in death. When untreated psychosis is also
accompanied by symptoms of paranoia and when it is associated with
substance abuse, the risk of violence is increased. Importantly, the
risk of violence is reduced with appropriate treatment.\9\ \10\
Moreover, people with SMI are 11 times more likely than the general
population to be victims of violence.\11\ Therefore, NIMH has planned
several new research initiatives, ramping up the Institute's commitment
to early treatment in order to reduce this period of untreated
psychosis to less than 12 weeks. These initiatives propose two
objectives: (a) improving detection of youth and young adults at high
risk for psychosis; and (b) reducing the duration of untreated
psychosis in community treatment settings.
IMPROVING PUBLIC HEALTH
When violence is associated with mental illness, it is most often
self-directed. Approximately 5 percent of individuals with
schizophrenia will die by suicide during their lifetime, a rate 50-fold
greater than the general population.\12\ Furthermore, suicide is the
10th leading cause of death in the United States, accounting for the
loss of more than 38,000 American lives each year, more than double the
number of lives lost to homicide.\13\ NIMH is spearheading several
initiatives intended to reduce and prevent suicide, such as taking a
lead role with The National Action Alliance for Suicide Prevention, a
public-private partnership tasked with developing the next National
Strategy for Suicide Prevention. Alongside the Jed Foundation, NIMH is
co-chairing the Action Alliance's Research Task Force (RTF), which is
developing a National Research Agenda to reduce suicide morbidity
(attempts) and mortality (deaths) by at least 20 percent in 5 years,
and 40 percent or more in 10 years. The RTF aims to release the Agenda
in September 2013.
One of the most notable and disturbing increases in suicide over
the past decade has occurred among the Nation's returning military
veterans. To counter this trend, NIMH has partnered with the Department
of the Army to conduct the Army Study to Assess Risk and Resilience in
Servicemembers (Army STARRS) Project--the largest study of mental
health risk and resilience ever conducted among military personnel.
Army STARRS seeks to identify factors that both protect soldiers'
mental health and those that put a soldier's mental health at risk. The
goal is to provide empirical evidence to help the Army develop targeted
prevention and treatment strategies. Army STARRS has established a data
enclave that integrates the administrative records of the 1.6 million
soldiers who served between 2004 and 2009. In addition, Army STARRS
includes a series of studies involving soldiers currently serving on
active duty. Most of these studies have now finished enrolling subjects
and the data are being analyzed.
NIMH, along with other NIH Institutes and the Departments of
Defense, Education, and Veterans Affairs are contributing to the
development of the National Research Action Plan (NRAP), pursuant to
Executive Order, ``Improving Access to Mental Health Services for
Veterans, Service Members, and Military Families'' (http://
www.whitehouse.gov / the-press-office / 2012 / 08 / 31/executive-order-
improving-
access-mental-health-services-veterans-service). NRAP will
strategically inform planning for future federally funded research
related to mental health and traumatic brain injury among veterans and
soldiers. NRAP will address post-traumatic stress disorder, depression,
suicide prevention, and some aspects of substance abuse prevention and
treatment.
THE FUTURE OF MENTAL HEALTH RESEARCH
On April 2, President Obama proposed the Brain Research through
Advancing Innovative Neurotechnologies (BRAIN) Initiative (http://
www.nih.gov/science/brain/index.htm), a bold plan not only to transform
our fundamental understanding of the brain, but also to revolutionize
both our approach to brain research and our understanding of brain
disorders. BRAIN will encourage the development of innovative
technology necessary for monitoring the activity of millions of brain
cells simultaneously and translate that activity into circuit diagrams
and algorithms. This effort will advance our understanding of how the
brain works and fails to work, and how it can be repaired.
Research has taught us to detect diseases early and intervene
quickly to preempt later stages of illness. This year, we will avert
1.1 million deaths from heart disease because we have not waited for a
heart attack to diagnose and treat coronary artery disease.\14\ Our
best hope of reducing mortality from mental illness and other brain
disorders will come from realizing that just like other medical
disorders, we need to diagnose and intervene before the symptoms become
manifest. Our investments today ensure a healthy tomorrow.
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\1\ Substance Abuse and Mental Health Services Administration.
``Results from the 2009 National Survey on Drug Use and Health: Mental
Health Findings'' (Office of Applied Studies, NSDUH Series H-39, HHS
Publication No. SMA 10-4609). Rockville, MD: Substance Abuse and Mental
Health Services Administration, 2010.
\2\ The World Health Organization. ``The global burden of disease:
2004 update,'' Table A2: Burden of disease in DALYs by cause, sex and
income group in WHO regions, estimates for 2004. Geneva, Switzerland:
WHO, 2008.
\3\ Insel TR. Assessing the economic cost of serious mental
illness. ``Am J Psychiatry.'' 2008 Jun;165(6):663-5.
\4\ Soni A. ``The Five Most Costly Conditions, 1996 and 2006:
Estimates for the U.S. Civilian Noninstitutionalized Population.''
Statistical Brief #248. July 2009. Agency for Healthcare Research and
Quality, Rockville, MD.
\5\ Bloom DE, Cafiero ET, Jane-Llopis E, Abrahams-Gessel S, Bloom
LR, Fathima S, Feigl AB, Gaziano T, Mowafi M, Pandya A, Prettner K,
Rosenberg L, Seligman B, Stein A, Weinstein C. ``The Global Economic
Burden of Non-communicable Diseases.'' Geneva, Switzerland: World
Economic Forum, 2011.
\6\ Druss BG, Zhao L, Von Esenwein S, Morrato EH, Marcus SC.
Understanding excess mortality in persons with mental illness: 17-year
follow up of a nationally representative U.S. survey. ``Med Care.''
2011 Jun;49(6):599-604.
\7\ Wang PS, Berglund PA, Olfson M, Kessler RC. Delays in initial
treatment contact after first onset of a mental disorder. ``Health Serv
Res.'' 2004 Apr;39(2):393-415.
\8\ Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T.
Association between duration of untreated psychosis and outcome in
cohorts of first-episode patients. ``Arch Gen Psychiatry.'' 2005 Sep
62:975-983.
\9\ Swanson JW, Swartz MS, Van Dorn RA, Volavka J, Monahan J,
Stroup TS, McEvoy JP, Wagner HR, Elbogen EB, Lieberman JA; CATIE
investigators. Comparison of antipsychotic medication effects on
reducing violence in people with schizophrenia. ``Br J Psychiatry.''
2008 Jul;193(1):37-43.
\10\ Steadman HJ, Mulvey EP, Monahan J, Robbins PC, Appelbaum PS,
Grisso T, Roth LH, Silver E. Violence by people discharged from acute
psychiatric inpatient facilities and by others in the same
neighborhoods. ``Arch Gen Psychiatry.'' 1998 May;55(5):393-401.
\11\ Teplin, LA, McClelland, GM, Abram, KM & Weiner, DA. Crime
victimization in adults with severe mental illness: comparison with the
National Crime Victimization Survey. ``Arch Gen Psychiatry,'' 2005,
62(8), 911-921.
\12\ Hor K. & Taylor M. Suicide and schizophrenia: a systematic
review of rates and risk factors. ``J Psychopharmacol.'' 2010;24(4S):
81-90.
\13\ Centers for Disease Control and Prevention, National Center
for Injury Prevention and Control. Web-based Injury Statistics Query
and Reporting System (WISQARS): www.cdc.gov/ncipc/wisqars accessed May
2013.
\14\ Vital Statistics of the United States, CDC/National Center for
Health Statistics. (2011, August). Age-adjusted Death Rates for
Coronary Heart Disease (CHD). National Heart Lung and Blood Institute.
Retrieved January 23, 2013, from http://www.nhlbi.nih.gov/news/
spotlight/
success/conquering-cardiovascular-disease.html.
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______
Prepared Statement of Martha J. Somerman, D.D.S., Ph.D., Director,
National Institute of Dental and Craniofacial Research
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of Dental and
Craniofacial Research (NIDCR) of the National Institutes of Health
(NIH). The fiscal year 2014 NIDCR budget of $411,515,000 includes an
increase of $1,568,000 over the comparable fiscal year 2012 level of
$409,947,000.
When NIDCR was established as a research home for oral health in
the mid-20th century, it focused primarily on oral infectious diseases
like tooth decay and periodontal disease. Today, the Institute
maintains a diverse and productive research portfolio that extends
beyond infections in the mouth. In keeping with its mission to improve
the Nation's oral health, the breadth of NIDCR-funded research includes
basic science studies aiming to understand development, maintenance,
and regeneration of tissues of the face and head; novel preventive,
diagnostic, and treatment approaches for oral infections and oral
cancer; investigating the role the mouth plays as an indicator of
overall health; and community-led studies of issues related to dental
care.
REALIZING PERSONALIZED ORAL HEALTH
Personalized health, aiming to individualize care based on a
person's unique genetic, environmental, and clinical profile, is not
new: dentists and physicians have long recognized variations among
patients, and they have provided customized care based on the history,
environmental exposure, and behavioral components that shape a person's
health. However, new technologies offer additional strategies. For
example, the NIDCR investment in molecular diagnostics using saliva is
a key step toward advancing personalized care. As a diagnostic fluid,
saliva has long been recognized to have many advantages over blood.
These include simple, non-invasive collection; the potential for lower
testing costs; portability; and application at or near the site of
patient care, maximizing convenience and allowing the results to be
available immediately to the patient. Recent progress comes from NIDCR-
supported scientists that developed a miniaturized, portable biochip
that can analyze small volumes of saliva. During the first phase of
this project, the researchers found promising predictive markers for
cardiac events. Other research identified the presence, in saliva, of
disease-related proteins and RNAs for oral cancers, Sjogren's syndrome,
and conditions such as periodontal disease.
Beyond supporting the development of molecular-based tools to
individualize care, NIDCR appreciates the important role of behavior
and environment in determining an individual's health status. As
trusted providers in a private setting, dentists have an extraordinary
opportunity to communicate to their patients the health risks of
behaviors such as alcohol and tobacco use. NIDCR-funded projects are
currently exploring how dental providers can help their patients by
providing smoking-cessation advice.
PROGRESS IN ORAL DISEASES: CANCER
The 5-year relative survival rate for oral and pharyngeal cancer is
approximately 60 percent, which is among the lowest for all major
cancers.\1\ This outlook is significantly worse for African Americans,
who face a 5-year relative survival rate close to 40 percent. In
addition to bringing behavioral science tools and expertise to bear on
this problem, NIDCR aims to initiate and lead an NIH-wide effort in
oral premalignancy identification and oral cancer prevention. The
multi-pronged approach weaves together scientific advances in molecular
profiling with clinical testing of the FDA-approved drug rapamycin for
its effectiveness against certain cancers of the head and neck. Also,
in fiscal year 2014 NIDCR will launch an initiative supporting research
on a unique type of cell capable of initiating oral cancer, as
therapies targeting these cells could potentially eliminate the
``root'' of the cancer.
Infection with human papillomavirus (HPV) is an increasingly
recognized risk factor for distinct forms of oral and pharyngeal
cancer. NIDCR remains vigilant to this rising public health concern.
The incidence of HPV-linked oral cancers in the United States has been
increasing at a rapid rate--by 225 percent from 1998 to 2004, and now
37 percent of oral and pharyngeal cancers are HPV-associated
cancers.\2\ Because the FDA-approved HPV vaccine Gardasil is effective
against the particular strains of HPV implicated in oral cancers, NIDCR
is supporting efforts to determine the potential benefit of this
vaccine in preventing these terrible diseases.
PROGRESS IN ORAL DISEASES: PAIN
NIDCR has a long-standing interest in the understanding and
management of chronic pain. In 2012, the Institute launched the second
phase of Orofacial Pain: Prospective Evaluation and Risk Assessment
(OPPERA), the first-ever large, prospective clinical study to identify
risk factors for temporomandibular joint disorder (TMJD). OPPERA II
will follow more than 3,000 initially pain-free individuals for three
to 5 years. OPPERA II will build upon OPPERA I and further explore risk
factors and genome-wide markers for chronic TMJD as well as for several
frequently overlapping pain conditions. Also in 2012, NIDCR partnered
with the National Institute of Neurological Disorders and Stroke to
host a workshop focused on identifying innovative scientific approaches
to the study of chronic overlapping pain conditions. Together, these
efforts are expected to have an impact not only on TMJD, but also on
other chronic pain conditions including fibromyalgia, irritable bowel
syndrome, chronic headache, vulvodynia, and chronic fatigue syndrome.
In addition, NIDCR co-sponsored a meeting in 2013 with two other NIH
Institutes to explore opportunities to utilize contemporary and
integrative approaches in understanding TMJ structure and function,
including novel imaging and molecular diagnostic techniques.
SYSTEMS APPROACHES TO UNDERSTANDING ORAL HEALTH
Oral tissues and fluids have remarkable protective roles, dependent
on human components and those of oral bacteria. The NIH Human
Microbiome Project (HMP) has created unprecedented opportunity to learn
much more. NIDCR is harnessing HMP knowledge and tools to define the
overlapping and unique roles of the oral microbiota in oral diseases
and immune function--such as in susceptibility to autoimmune diseases
and cancer--and in other systemic conditions like metabolic syndrome, a
cluster of co-occurring conditions including increased blood pressure,
blood sugar levels, body fat, and cholesterol levels that can raise the
risk of heart disease, stroke, and diabetes. NIDCR is investing
resources in new approaches to understand the properties of the vast
majority (more than 80 percent) of the microbial universe in our mouths
that cannot be grown in the laboratory. These studies will provide
insights into interactions among microbes and with human cells,
potentially leading to the development of novel strategies for
prevention, diagnosis, and treatment of oral diseases.
Genome-wide association studies, or GWAS, are another example of
the broad utility of systems approaches for investigating oral health
biology. GWAS methods combine human genome sequencing and high-speed
computing, to scan the entire genome for disease triggers and factors.
In the realm of oral health, GWAS suggest that the risk for dental
caries arises from interplay between genetic factors, home fluoride
exposure levels, and in some cases, taste preferences. Further analyses
may point to common risk factors for dental caries and other conditions
such as diabetes and cardiovascular disease. NIDCR-funded genetic
studies of craniofacial development and birth defects have yielded
information on the causes of cleft lip and palate and craniosynostosis,
and this research will continue to be a focus moving forward.
NEW DIRECTIONS IN ORAL HEALTH RESEARCH
Minding workforce trends and the importance of interdisciplinary
science to health promotion, NIDCR recognizes the need for
investigators representing a range of scientific areas to conduct
research in dental, oral, and craniofacial health. NIDCR is
particularly engaged with the needs and contributions of practitioners,
whose participation in research could cut the time it takes for
laboratory research to be applied for patients. In 2005, NIDCR launched
the Practice-Based Research Network, or PBRN, and the second, 7-year
phase began in April 2012. This powerful ``real world'' research
network is recruiting practitioners in every State--with a goal of
involving at least 5,000--to propose and perform clinical studies on
topics important to dentistry. Because the research is conducted by
clinicians in their own practices, dentists are more likely to accept
and adopt the findings. The expected result is nothing short of a
transformation of dental practice--one that will yield more
individualized and evidence-based treatment and prevention, to the
benefit of millions of Americans.
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\1\ Siegel et al., (2013) Cancer statistics, 2013. ``CA: A Cancer
Journal for Clinicians.'' 63 (1) 11-30.
\2\ Gillison ML et al. (2012) ``JAMA'';307,693-703; Jemal A et al.
(2013) ``J Natl Cancer Inst.''
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______
Prepared Statement of Griffin P. Rodgers, M.D., M.A.C.P., Director,
National Institute of Diabetes and Digestive and Kidney Diseases
Mr. Chairman and members of the committee: I am pleased to present
the President's fiscal year 2014 Budget request for the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the
National Institutes of Health (NIH). The fiscal year 2014 budget
includes $1,811,786,000, which is $18,080,000 above the comparable
fiscal year 2012 appropriation of $1,793,706,000. Complementing these
funds is an additional $150,000,000 also available in fiscal year 2014
from the Special Statutory Funding Program for Type 1 Diabetes
Research. NIDDK supports research on a wide range of common, chronic,
costly, and consequential diseases and health problems that affect
millions of Americans. These include diabetes and other endocrine and
metabolic diseases; digestive and liver diseases; kidney and urologic
diseases; blood diseases; obesity; and nutrition disorders.
TODAY'S BASIC SCIENCE FOR TOMORROW'S BREAKTHROUGHS
NIDDK-supported basic science research is achieving remarkable
advances and building the foundation for previously unimaginable
strategies to improve health and quality of life. Among these advances,
recent research into biological processes showed that two newly
discovered molecules--irisin and TRPV4--regulate energy expenditure in
mice. Irisin was shown to promote energy expenditure (calorie burning),
and reduced obesity and type 2 diabetes. Mice genetically engineered to
lack TRPV4 had increased energy expenditure without differences in food
intake, physical activity, or body temperature. If these findings are
extended to humans, administration of irisin or targeting of TRPV4
could be potential new therapeutic approaches for obesity and type 2
diabetes. In addition, newly identified brown fat progenitor cells and
factors that regulate brown fat development may lead to new obesity
therapies that coax cells in white fat tissue to burn calories faster,
like brown fat. The microorganisms that inhabit the gastrointestinal
tract are important factors in maintaining or tipping the balance
between digestive health and disease. Investigators have also reported
that early exposure to ``friendly'' microbes protects against
inflammatory bowel disease in animal models. Investigating the
different types of bacteria that reside in the intestines, researchers
have discovered surprising links to diet, diversity with respect to age
and geographic location, fatty liver disease, and antibiotic exposure.
Scientists supported by our Institute have shown that pancreatic b
cells can revert to an earlier developmental stage and lose their
ability to produce insulin; thus, approaches that save cells that have
regressed and restore them to become b cells again could be an
effective way to treat type 2 diabetes. Other scientists have
illuminated the complex system of regulation surrounding kidney
fibrosis following injury, and identified potential targets for further
strategies aimed at preventing and possibly reversing kidney fibrosis.
For example, one molecule, called microRNA-21, was found to be highly
elevated in two mouse models of kidney disease soon after injury but
before fibrosis appeared. Mice engineered to lack the microRNA-21 gene
showed diminished fibrosis in response to kidney injury. This molecule,
which is found in humans with kidney injury, represents a potential
target for antifibrotic therapies in kidney disease.
NIDDK will continue support for basic research across the
Institute's mission, to gain further insights into health and disease
and propel new ideas for interventions. Areas of emerging opportunity
include research on human b cells toward the goal of developing cell
replacement therapies; genetic analyses to identify genes and gene
regions associated with inflammatory bowel disease; identification of
environmental triggers of type 1 diabetes in genetically susceptible
newborns; and development of blood and urine tests to better predict
patients who will have rapid progression of kidney disease or worsening
of heart disease.
TRANSLATIONAL AND CLINICAL SCIENCE
Through innovative design and rigorous testing of interventions--
whether in the operating room, doctor's office, or home or community
settings--NIDDK-supported researchers are improving lives with new
approaches to prevent, treat, and reverse diseases and disorders. For
example, investigators have recently reported that weight loss and
increased physical fitness slow decline in mobility in overweight or
obese adults with type 2 diabetes. Invasive and costly tests commonly
performed in women before surgery for stress urinary incontinence may
not be necessary--information that women and their physicians can
consider in planning treatment. This could result in fewer unnecessary
procedures and a savings in healthcare costs. Additional research has
shown that interventions to prevent type 2 diabetes in people at high
risk for the disease are a very cost-effective way to improve their
health and quality-of-life.
Because many diseases within our mission disproportionately affect
certain populations, we will also continue to seek insights and answers
to health disparities. As just a few examples of our many clinical
studies, Institute-supported scientists are conducting two large-scale,
long-term observational studies of chronic kidney disease (CKD), the
Chronic Kidney Disease in Children (CKiD) Study and the Chronic Renal
Insufficiency Cohort (CRIC) Study, to address a wide range of
scientific questions focused on prediction and mechanisms of CKD
progression in both children and adults. Several efforts are
translating CKD research into improved clinical outcomes such as
decision support interventions to improve renal replacement therapy
preparation. Among multifaceted efforts to meet the challenge of
obesity is a consortium studying lifestyle interventions for overweight
and obese pregnant women, to improve the health of both mother and
child. The Institute continues to support clinical studies for a range
of liver diseases including a multicenter research network planning
trials of different treatment strategies for hepatitis B, including
comparative effectiveness research. The MERIT-UC study investigators
are conducting a multicenter trial to investigate the safety and
efficacy of methotrexate (a drug also used to treat some forms of
cancer and rheumatoid arthritis) in adult patients with active
ulcerative colitis. The Glycemia Reduction Approaches in Diabetes: A
Comparative Effectiveness study has as its overarching goal to
understand the relative effectiveness of different medications in
combination with metformin, and whether introducing them sequentially
or initially in combination is most effective in maintaining glycemic
goals over time in patients with type 2 diabetes. To maximize the reach
and benefits of interventions proven successful in clinical trials,
NIDDK will sustain support for translational research.
RECRUITING AND RETAINING DIVERSE SCIENTIFIC TALENT
NIDDK will continue programs to train and support researchers at
all stages of their careers, and to ensure that we benefit from the
best scientific minds. This year, NIDDK held its 11th annual Network of
Minority Research Investigators workshop to encourage and facilitate
participation of underrepresented racial and ethnic minority groups in
the conduct of biomedical research. Several NIDDK-sponsored programs
provide opportunities for minority students to obtain research
experience. For example, NIDDK's Short-Term Education Program for
Underrepresented Persons, or STEP-UP, provides research education
grants to seven institutions to coordinate three high school and four
undergraduate STEP-UP programs that enable students to gain summer
research experience and training. STEP-UP and the NIH Building
Infrastructure Leading To Diversity (BUILD) Consortium will work to
identify resources which may be shared and to exchange lessons learned/
best practices.
INTEGRATING SCIENCE-BASED INFORMATION INTO PRACTICE: EDUCATION AND
OUTREACH
NIDDK also will continue to support education, outreach, and
awareness programs. In 2012, NIDDK, in collaboration with NLM, launched
the LiverTox database--a free source of evidence-based information for
healthcare professionals and for researchers studying liver injury
associated with prescription and over-the-counter medications, herbal
products, and dietary supplements. Likewise, in 2012, NIDDK
collaborated with Home Box Office to develop ``The Weight of the
Nation'' documentary series showing how obesity affects the Nation's
health, and how interventions can turn the tide against obesity and its
complications. In addition, NIDDK's National Kidney Disease Education
Program collaborated with the American Diabetes Association's ``Live
Empowered'' program, the National Coalition of Pastors' Spouses, and
Chi Eta Phi Sorority, Incorporated, to kick off the first nationwide
``Kidney Sundays'' event to raise awareness of kidney disease risk
factors among African Americans.
In closing, NIDDK's future research investments will be guided by
five principles: maintain a vigorous investigator-initiated research
portfolio; support pivotal clinical studies and trials; preserve a
stable pool of new investigators; foster research training and
mentoring; and disseminate science-based knowledge through education
and outreach programs.
______
Prepared Statement of Judith H. Greenberg, Ph.D., Director, National
Institute of General Medical Sciences
Mr. Chairman and members of the committee: I am pleased to present
the President's budget for the National Institute of General Medical
Sciences (NIGMS) of the National Institutes of Health (NIH). The fiscal
year 2014 budget of $2,401,011,000 includes a decrease of $24,511,000
below the comparable fiscal year 2012 level of $2,425,522,000.
Basic discovery for better health is the past, present, and future
of NIGMS. Today, amid the breakneck speed of progress in biomedical and
information science technology, truly phenomenal opportunities for
progress are at our doorstep.
In one recent example of the merit of joining the biological and
information sciences, scientists with the NIGMS-led NIH
Pharmacogenomics Research Network (PGRN) devised a computer algorithm
to sift through millions of reports to the U.S. Food and Drug
Administration to predict dangerous, yet unsuspected interactions
between medications such as those between antidepressants and a common
blood-pressure medication. In another case, researchers with the
Institute's flagship Protein Structure Initiative (PSI) solved the
three-dimensional atomic structure of the molecule on the surface of
brain cells that attaches to opioids and is centrally involved in
pleasure, pain, addiction, depression, psychosis, and related
conditions. By linking these conditions in molecular terms, the
research may well lead to better, more targeted drug therapies for a
range of brain-related conditions. A third example comes from
investigators with the NIGMS-funded Models of Infectious Disease Agent
Study (MIDAS) program. They showed that methicillin-resistant
``Staphylococcus aureus'', or MRSA, infections are better prevented
when hospitals cooperate and coordinate their infection control
procedures. This research points to policy-related measures that could
have a significant impact on public health.
FROM BENCH TO BEDSIDE AND BACK
For several decades, NIGMS has provided a home for research
conducted in emergency care settings. The Institute's burn and trauma
centers have made many discoveries that have been implemented
clinically. These include the development of artificial skin for burn
victims, nutritional standards for the care of severely injured
patients, and new understanding of how inflammation affects injury and
healing in people who have experienced severe physical trauma.
This past year, NIGMS announced the formation of the Office of
Emergency Care Medicine (OECR). This office is the culmination of
several years of discussions between NIH and the emergency medicine
community, and responds to reports about the Nation's emergency medical
system issued in 2006 by the Institute of Medicine. Although OECR does
not have funding authority, it will provide agency-wide coordination
toward speeding diagnosis and improving care for the full spectrum of
conditions that require emergency treatment.
Another compelling example of the clinical relevance of NIGMS-
supported basic research is the Developmental Genome Anatomy Project
(DGAP), which employs a model of ``patient as laboratory.'' DGAP
scientists identify abnormalities in the DNA of people with a disorder
that is not well understood, and then follow up with laboratory studies
to further probe the molecular defect in animal models. One exciting
DGAP discovery is a prenatal diagnostics method that analyzes DNA in
amniotic fluid using customized whole-genome sequencing.
BASIC DISCOVERIES FOR BETTER HEALTH
NIGMS-supported research employs a range of non-human model
organisms to ask and answer questions about human biology. One example
is research to understand circadian rhythms, commonly known as the
biological clock. The foundation of knowledge gathered over the years
in this area of science is now coming together to help explain how
various diseases and conditions are influenced by the time of day.
Recent NIGMS-funded studies have shown that circadian rhythms have a
major influence on the production of the basic units of metabolism such
as amino acids, sugars, and fats. Researchers learned that about 60
percent of these essential metabolites that sustain and promote cell
health and growth are synchronized with the body's clock system. These
findings are important because of their connection to other NIGMS-
supported research established a link between circadian rhythms and
chronic conditions like diabetes and obesity, which involve activities
linked to time of day including eating, sleeping, and physical
activity. Integrating knowledge from basic metabolism and circadian
biology has implications for managing the many conditions related to
our biological clocks.
Aside from their use as models for basic cell biology, genetics,
and metabolism, bacteria are a focus of study for NIGMS-supported
researchers in another way: the study of bacterial communities called
biofilms. Many individual microbes do not cause disease; indeed, they
aid in normal digestion and perform other vital roles in the body. Yet,
when some otherwise non-harmful strains of bacteria assemble into a
film structure, they can clog medical devices like heart valves and
catheters. Using powerful microscopes and time-lapse imaging, NIGMS-
supported scientists watched biofilms form, as microbes joined together
to create slimy ribbons that ensnared other bacteria as they traveled
through narrow, fluid-filled tubes mimicking implanted medical devices.
The researchers were surprised to learn just how fast this clogging
occurred, and with no apparent warning. These research results could be
used toward the development of clog-resistant medical devices.
ENABLING TECHNOLOGY THAT ADVANCES DISCOVERY
Technology is a key driver of progress in biomedicine. NIGMS
considers its support of resource development a vital component of the
Institute's investment in allowing creative scientists to uncover new
knowledge and make breakthrough discoveries.
One example of NIGMS-supported resource development is the NIGMS
Biomedical Technology Research Centers program, a synergistic
interaction of technical and biomedical expertise. These Centers
promote the widespread and routine application of pioneering
technologies and methods, and apply them to a broad range of basic,
translational, and clinical research efforts. The resources--ranging
from electron microscopes to bioinformatics platforms to mass
spectrometers and other technologies--are used by thousands of NIH-
supported scientists each year.
A second example is the Institute's investment in research on
chemistry methods that can be used and re-purposed by both academia and
industry. In one recent instance, scientists used NIGMS research funds
to make a chemistry toolkit that can quickly and easily generate dozens
or even hundreds of versions of a single molecule, toward the testing
and refining of such molecules as potential drugs. This research is
important because companies are unlikely to sponsor the development of
broad-based resources like this. A key advantage of this new technique
is that it simplifies complicated and potentially hazardous chemical
reactions such that they can be automated and can be performed in a
water-based environment without the use of harmful chemicals.
STRATEGY FOR THE FUTURE
NIGMS has always planned strategically for the future, since
biomedical research is a long-term commitment to supporting creative
people to develop and test new ideas. Part of this process is keeping
an eye on the evolution of biomedicine as new tools emerge and new
disease threats come to light. In recent years, NIGMS has published
companion strategic plans that chart the Institute's course for
research and research training, noting the tight link between the two.
The Institute continues to invest funds and resources toward activities
that reflect the content of these plans. NIGMS strives for a healthy
balance within its scientific portfolio between small projects that are
conducted by individual scientists within their laboratories, and
larger consortia (like the PGRN, PSI, and MIDAS) that enable
researchers to work together on problems that call for a broader range
of expertise, samples, and resources than can be managed reasonably and
successfully by individual scientists.
NIGMS is pleased that many of its research and research training
efforts under way resonate so well with recommendations put forth last
year by the NIH Advisory Committee to the Director on NIH's role in
research training and in promoting a diverse biomedical workforce.
Toward building a strong evidence base in workforce-related issues,
NIGMS has funded grants that investigate factors contributing to gender
and ethnic/racial disparity in workforce representation, to increase
diversity. Emerging concepts include eliminating unconscious bias,
career flexibility, and the value of good mentoring. This growing body
of work will be pivotal to effecting change on a larger scale.
NIGMS recognizes its vital role in supporting basic research for
better health. In so doing, the Institute contributes in a sustained
fashion to the health of the American people and to maintaining
America's leadership role in science.
______
Prepared Statement of Alan E. Guttmacher, M.D., Director, ``Eunice
Kennedy Shriver'' National Institute of Child Health and Human
Development
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the ``Eunice Kennedy Shriver''
National Institute of Child Health and Human Development (NICHD). The
fiscal year 2014 budget of $1,339,360,000 includes an increase of
$20,417,000 over the comparable fiscal year 2012 level of
$1,318,943,000.
This past year, NICHD celebrated its 50th anniversary. Beyond
celebrating past accomplishments, this milestone inspired the
Institute, along with its many stakeholders, to identify compelling
scientific opportunities for the next decade. The Institute's future
research must build upon its strong foundation of scientific advances,
from better understanding of the basic mechanisms that transform cells
into healthy and effectively functioning individuals, to clinical
studies that improve the health and well-being of women, children,
families, and individuals with disabilities.
DEVELOPMENTAL BIOLOGY
Research in developmental biology helps to explain how individuals
develop and the origins of various diseases and conditions. Recently,
NICHD-funded scientists found that pregnant women with epilepsy who
took the prescription drug topiramate during their first trimester to
prevent seizures were at a slightly increased risk of having babies
with cleft lip. Intramural scientists recently used next-generation
gene sequencing techniques to discover new brain regions in an animal
model, once thought to be inert, which appear to be active in the
pineal gland, which controls the body's 24-hour wake-sleep cycle and is
integral to development. Advances in genetics and systems biology will
shed new light on human development, and provide critical underpinnings
for emerging fields such as regenerative medicine.
DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE
Complex interactions among biological and external factors,
starting before conception, can influence health across the life
course, and even across generations. NICHD researchers discovered a
genetic pathway common to the rapid growth of healthy fetuses and the
uncontrolled cell division of cancer, shedding light on both normal
development and the genetic bases of common cancers. Understanding the
developmental origins of health and disease will benefit from
interdisciplinary and global studies and, ultimately, can be applied to
prevent, treat, or even reverse chronic conditions such as obesity,
diabetes, and cognitive deterioration.
PREGNANCY AND PREGNANCY OUTCOMES
Achieving a better understanding of pregnancy processes and fetal
development can pave the way for predicting and preventing poor
pregnancy outcomes as well as improving lifelong health for both women
and infants. A new NICHD-funded study reported that pregnant women's
exposure to the flu was associated with a nearly four-fold increased
risk that their children would develop bipolar disorder in adulthood.
This information may encourage and increase the use of prevention
strategies, such as the flu vaccine. Another study found that women who
develop gestational diabetes during pregnancy can greatly decrease
their risk of developing type 2 diabetes later in life by maintaining a
healthy diet in the years following pregnancy. Targeted areas for
future research include obtaining further understanding of how to
promote healthy pregnancies and unraveling the complex causes of
stillbirth and prematurity.
REPRODUCTION
Reproductive health is an essential element of personal well-being
across the lifespan, and necessary to ensuring the health of future
generations. NICHD-supported research found that the hormone progestin,
often given as a first step in infertility treatment for polycystic
ovary syndrome, unexpectedly decreased the odds of conception and
giving birth. Discoveries such as this advance our understanding of
what works in clinical practice and what may have unintended
consequences and, at the same time, be used to identify potential new
diagnostic and therapeutic targets for managing critical aspects of
women's and men's reproductive health.
BEHAVIOR AND COGNITION
Human behaviors can contribute to positive health outcomes or
increase the risk of adverse ones. NICHD-funded researchers found that
when the mind is at rest, the electrical signals by which brain cells
communicate appear to travel in reverse, wiping out unimportant
information, while sensitizing cells for future learning. NICHD
research found that children who failed to acquire a particular math
skill, number system knowledge, in first grade scored well behind their
peers by seventh grade, pointing the way for targeted intervention when
it matters most. In another study, seven-month old babies who were
later diagnosed with autism took slightly longer to shift their gaze
than babies who developed normally, which may provide an early clue to
differences in their brain structure. Future basic and translational
research that combines neuropsychological, behavioral, and social
science perspectives will increase knowledge about the mechanisms that
underlie typical and atypical behavior and cognition.
PLASTICITY AND REHABILITATION
Plasticity, adaptive or maladaptive change at the cellular, tissue,
organ, or system levels, is at the core of human development and
rehabilitation. NICHD researchers have identified proteins in an animal
model that help fuse early-stage cells and eventually develop into
muscle cells. This finding has implications for understanding how to
repair and rehabilitate muscle tissue and how specialized cells
(osteoclasts) repair and maintain bones. The ongoing challenge for
scientists will be to generate additional knowledge about the
mechanisms of plasticity, and translate this knowledge into
interventions that can help individuals remodel, maintain, or enhance
functioning.
POPULATION DYNAMICS
Individuals, families, and communities are all critical units,
through which population-level factors interact with genetic and
environmental variables, influencing individual health across the
lifespan. An NICHD study demonstrated that the stresses of poverty
(e.g., financial worries, inadequate child care), were shown to lead to
impaired learning ability in children; high levels of stress hormones
influence the developing circuitry of children's brains, impairing
their executive functions. Another study, a landmark collaboration
among NICHD, other NIH Institutes and Centers, Federal agencies, and
private foundations, demonstrated that providing specialized housing
vouchers that enabled low-income women and children to move from
impoverished neighborhoods to those with relatively few poor residents
reduced extreme obesity and diabetes over time. Over the next decade,
research must continue to provide the comprehensive evidence needed for
what works and how to scale programs at the population level,
accounting for individual behaviors and biomedical factors, family and
community characteristics, and social forces.
CONDUCT OF SCIENCE
In the coming years, biomedical and biobehavioral researchers will
need to work as transdisciplinary teams, manage massive amounts of
data, and acquire new and diverse skill sets. The very breadth of
NICHD's mission requires us to create, train, and support such teams to
be able to fully translate our research advances into actions that
improve the health of women, children, families, and individuals with
disabilities.
______
Prepared Statement of Paul A. Sieving, M.D., Ph.D., Director, National
Eye Institute
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Eye Institute (NEI) of
the National Institutes of Health (NIH). The fiscal year 2014 budget of
$699,216,000 includes a decrease of $2,191,000 below the comparable
fiscal year 2012 level of $701,407,000. As the director of the NEI, it
is my privilege to report on the many research opportunities that exist
to reduce the burden of eye disease.
STRATEGIC PLANNING
``The NEI Challenge to Identify Audacious Goals in Vision Research
and Blindness Rehabilitation'' was a novel strategic planning
initiative designed to identify innovative, groundbreaking long-term
research goals. The challenge was open to anyone with an idea for a 10-
year audacious research goal including scientists, engineers,
clinicians, and the public. NEI used a new prize competition authority,
from the America COMPETES Reauthorization Act of 2010, to attract
attention and received more than 500 ideas for audacious goals. A
Federal review panel selected 10 winning entries for further
consideration. Then, more than 200 leading scientists and clinicians
met to further develop these ideas at the NEI Audacious Goals
Development Meeting held in February 2013. Afterwards, NEI announced an
audacious goal (Regenerate Neurons and Neural Connections in the Eye
and Visual System) and two high-priority areas (Molecular Therapy for
Eye Disease and the Intersection of Aging and Biological Mechanisms of
Eye Disease) at the Association for Research in Vision and
Ophthalmology meeting on May 5. NEI is now identifying the necessary
steps to boldly attack these research endeavors over the coming decade.
CLINICAL TRIALS
This month, NEI-supported investigators published results of the
Age-Related Eye Disease Study 2 (AREDS2), a large, multi-center
clinical trial designed to refine the antioxidant and mineral
supplement formulation that was evaluated in the original AREDS
clinical trial. The original Age-related Eye Disease Study (AREDS)
established that daily doses of vitamins C and E, beta-carotene, zinc,
and copper slows the progression to advanced age-related macular
degeneration (AMD), the leading cause of visual impairment and legal
blindness in older Americans. AREDS2 was undertaken for three reasons.
First, preliminary evidence indicated that Omega-3 fatty acids might be
beneficial. Second, beta-carotene, used in AREDS, was found to increase
lung cancer risk in cigarette smokers. Third, it was suggested that the
rather high zinc level in AREDS might cause minor side effects, such as
stomach upset. AREDS2 investigators found that adding Omega-3 fatty
acids, replacing beta-carotene with two other carotenoids, lutein and
zeaxanthin, and lowering zinc levels maintained, but did not improve
the effectiveness of the original formulation. Thus, changing the
carotenoid and lowering the zinc in original AREDS formulations offers
an equally effective alternative with fewer side effects. The AREDS2
study results provide physicians and patients with new information
about delaying or preventing vision loss from AMD.
In February 2013, the FDA approved the Argus II Retinal Prosthesis
System, a medical device capable of restoring ambulatory vision to
those blind from retinitis pigmentosa. Argus II consists of a miniature
video camera that is mounted on a pair of glasses. A processing unit
worn on a belt converts images captured by the camera into electrical
impulses that are wirelessly transmitted to a 60-electrode grid
implanted in the eye. Users perceive the electrical impulses as
patterns of light that produce visual information. The Argus II,
developed by Second Sight, Inc., was made possible through more than a
decade of clinical trial support from NEI.
TRANSLATIONAL RESEARCH
Retinitis pigmentosa (RP) is a group of rare, degenerative diseases
that result from mutations in any one of 40 genes that function in rod
photoreceptor cells in the retina. These cells form our peripheral
vision and allow us to see in dim and dark environments. As RP
progresses, patients experience night blindness and severely restricted
visual fields. For reasons that are not understood, the loss of rods
eventually leads to the degeneration and death of cones, the
photoreceptor cells in the central portion of the retina that allow us
to perceive fine visual detail and color. Without central vision, it is
impossible to perform essential tasks of daily life such as reading,
driving, walking without assistance, or recognizing faces and objects.
Vision researchers have long sought a therapeutic approach that can
address multiple RP genotypes. However, current efforts with gene
therapy address only one specific gene defect at a time. In a highly
novel approach that could be applied to most, if not all, forms of RP,
NEI-supported investigators genetically reprogrammed rods to become
cone-like cells in a rodent model of RP. This approach reduced rod cell
function but preserved cone cells. Although such a treatment would
leave patients with limited peripheral vision and night blindness, this
would be preferable to the added debilitating loss of central vision
for the estimated 200,000 Americans who live with RP.
NEI-supported investigators have developed a potential new
treatment to prevent proliferative vitreoretinopathy (PVR) a sight-
threatening complication of retinal detachment that requires prompt
surgical treatment. PVR occurs in about 10 percent of retinal
detachments, resulting in permanent scarring of the retina. In this
condition, retinal pigment epithelial (RPE) cells, which line the
neural retina, migrate through the retinal detachment into the vitreous
fluid where they rapidly multiply, dedifferentiate and contribute to
the formation of an abnormal membrane on the surface of the retina.
This membrane eventually contracts, pulling at the retina and forming a
larger detachment. PVR causes heavy scarring of the retina and severe
visual impairment. NEI investigators identified seven classes of
biological growth factors and regulatory proteins that promote the
proliferation and contraction of the RPE-derived membrane in an animal
model of PVR. By inhibiting the expression of these biological factors,
the investigators prevented PVR. This study provides insight into the
causes of PVR and proof-of-concept for treating the condition.
The cornea, the outer protective layer of the eye, is amazingly
resilient to infection. By exposing cultured human corneal cells to
bacteria, NEI researchers identified a class of peptides important in
the cornea's defense against bacterial infection. Blocking these
peptides in a rodent model led to a marked increase in corneal
infections. Synthetic variations of these peptides effectively killed
bacteria that lead to flesh-eating disease and strep throat, staph
infections, diarrhea, and cystic fibrosis associated lung infections.
The findings could lead to a powerful new class of low-cost antibiotics
at a time when antibiotic resistance to existing agents is of growing
concern.
______
Prepared Statement of Linda S. Birnbaum, Ph.D., D.A.B.T., A.T.S.,
Director, National Institute of Environmental Health Sciences
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of
Environmental Health Sciences (NIEHS) of the National Institutes of
Health (NIH). The fiscal year 2014 NIEHS budget of $691,348,000
includes an increase of $7,051,000 from the comparable fiscal year 2012
level of $684,297,000.
INTRODUCTION
In fiscally challenging times for science, NIEHS is finding
innovative ways to maximize its investments through strategic planning,
collaborative research, and focused translation of science. For
example, NIEHS grantees have discovered a key mechanism by which
dietary omega-3 fatty acids (fish oils) could reduce the growth and
spread of cancer, which kills 580,000 Americans a year.\1\ New findings
from the NIEHS Sister Study show that even moderate physical activity
can reduce breast cancer risk,\2\ and that estrogen may help offset
effects of obesity and alcohol on risk.\3\
COLLABORATIVE RESEARCH
NIEHS develops and leads multi-disciplinary collaborations in areas
such as the Gulf Oil spill, breast cancer and the environment,
nanotechnology, bisphenol A, and science data management. In
partnership with the Substance Abuse and Mental Health Services
Administration, the NIEHS Gulf Long-term Follow-up (GuLF) Study of
33,000 men and women will assess mental health trajectories, resiliency
and coping, and mental healthcare needs of participants. NIEHS has
invested $30 million from 2009 to date working with Federal partners
and the Nation's leading researchers to fill data gaps and resolve
controversies over the human health effects of exposure to low levels
of BPA. Nearly 150 papers have resulted from this effort so far.\4\
Recent observational human studies \5\ show that early life exposures
to BPA can potentially lead to diseases or health problems in adulthood
such as prostate and breast cancer, obesity, diabetes, and
cardiovascular, neurobehavioral, and reproductive disorders. Work of
the Engineered Nanomaterials Grand Opportunity (Nano GO) Consortium of
13 laboratories now provides investigators with standardized methods
for predicting the toxicity of selected nanomaterials.\6\ \7\ NIEHS is
a partner in the new National Consortium for Data Science that aims to
address the challenges of collecting, sharing, and using large, diverse
datasets. At its recent summit, genomic and data scientists drafted
recommendations for translating genomic data into better, more
affordable healthcare by developing new ways to collect, manage,
analyze, and apply massive amounts of data into tools for scientific
discovery and economic growth.
SCIENTIFIC ADVANCES
NIEHS's investigator-initiated research provides critical advances
in environmental health and basic sciences. New findings suggest that
Vitamin D may reduce the risk of uterine fibroids,\8\ a condition that,
according to NIH, afflicts up to 80 percent of American women, causes
more than 200,000 hysterectomies each year, and results in direct
health costs of $2.1 billion. A recent study points to exposure to
polybrominated diphenyl ethers in flame retardants as a factor in
increased risk of Parkinson's disease.\9\ A new analysis of the
scientific literature shows that exposure to increased levels of
particulate matter during pregnancy can lead to greater risk of low
birth weight babies,\10\ putting them at risk of poor health in
childhood and adulthood.
Exposure to toxic substances in the environment accrues huge costs
in human suffering, and results in economic costs to individuals and
society; NIEHS-funded studies illustrate this dual burden. Each year in
Europe, 1.8 million children suffer unsafe prenatal methylmercury
exposures that affect brain development, mostly from fish in mothers'
diets. Preventing such exposures could save the European Union 8 to 9
billion euros per year in lost earning potential of these children.\11\
In a study of approximately 12.5 million elderly Medicare
beneficiaries, researchers found a consistent increase in costly
respiratory hospitalizations with increasing outdoor temperatures.\12\
STAKEHOLDER TRANSLATION
Just as scientific rigor is required to generate sound research
findings, vigorous approaches are needed to translate these findings to
stakeholders. In 2012, NIEHS released a strategic plan that identifies
key goals for the next 5 years that will provide the rubric for NIEHS
to achieve its vision as a catalyst for the application of state-of-
the-art biomedical research to the most critical environmental health
problems. NIEHS ``talks the talk'' by committing to effective research
translation in its strategic plan, and ``walks the walk'' through
engagement and translation activities with the American public.
Community Forums around the United States allow the public to raise
environmental health concerns with the NIEHS director. In November
2012, NIEHS held its first virtual Community Forum on environmental
exposures and childhood obesity, using social media and webcasting to
reach 600 viewers and spark 1.5 million tweets. In a March forum in
Seattle, residents voiced concerns about a site along the Duwamish
River that is one of the most polluted in the U.S., as well as home to
low-income and recent immigrants, and fishing grounds of three
Northwest Tribes. In February, the NIEHS-led Interagency Breast Cancer
and Environmental Research Coordinating Committee released
``Prioritizing Prevention,'' recommendations for reducing environmental
exposures and modifying lifestyle factors implicated in breast cancer.
NIEHS provides critical Federal and global leadership to advance
science on how the environment affects people's health to promote
healthier lives.
---------------------------------------------------------------------------
\1\ Zhang G, et al., Epoxy metabolites of docosahexaenoic acid
(DHA) inhibit angiogenesis, tumor growth, and metastasis. Nature. April
3, 2013. Published online at: http://www.pnas.org/content/early/2013/
04/03/1304321110.
\2\ McCullough LE, et al., Fat or fit: the joint effects of
physical activity, weight gain, and body size on breast cancer risk.
Cancer. Oct. 1, 2012, 118(19):4860-8. Published online at: http://
www.ncbi.nlm.nih.gov/pubmed/22733561.
\3\ Hong J, Holcomb VB, Kushiro K, Nunez NP. Estrogen inhibits the
effects of obesity and alcohol on mammary tumors and fatty liver. 2011.
Int J Oncol 39(6):1443-1453. Published online at: http://
www.ncbi.nlm.nih.gov/pubmed/21850368.
\4\ http://www.niehs.nih.gov/research/resources/bpa-related/
index.cfm.
\5\ Li D, et al., Occupational exposure to bisphenol-A (BPA) and
the risk of self-reported male sexual dysfunction. Hum Reprod. 2010
Feb;25(2):519-27. Published online at: http://www.ncbi.nlm.nih.gov/
pubmed/19906654.
\6\ Xia T, et al., Interlaboratory Evaluation of ``In Vitro''
Cytotoxicity and Inflammatory Responses to Engineered Nanomaterials:
The NIEHS Nano GO Consortium. Environ Health Perspect. 2013 May 6.
[Epub ahead of print] Published online at: http://www.ncbi.nlm.nih.gov/
pubmed/23649538.
\7\ Bonner JC, et al., Interlaboratory Evaluation of Rodent
Pulmonary Responses to Engineered Nanomaterials: The NIEHS Nano Go
Consortium. Environ Health Perspect. 2013 May 6. [Epub ahead of print]
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/23649427.
\8\ Baird DD, Hill MC, Schectman JM, Hollis BW. 2013. Vitamin D and
the risk of uterine fibroids. ``Epidemiology''; 24(3):447-453.
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/23493030.
\9\ Bradner JM, et al., Exposure to the polybrominated diphenyl
ether mixture DE-71 damages the nigrostriatal dopamine system: Role of
dopamine handling neurotoxicity. Exp Neurol 2013, 241:138-147.
Published online at: http://www.ncbi.nlm.nih.gov/pubmed/23287494.
\10\ Dadvand P, et al., Maternal exposure to particulate air
pollution and term birth weight: a multi-country evaluation of effect
and heterogeneity. Environ Health Perspect; 2013 [Online 6 February
2013]. Published online at: http://ehp.niehs.nih.gov/1205575/.
\11\ Bellanger M, et al., Economic benefits of methylmercury
exposure control in Europe: Monetary value of neurotoxicity prevention.
Environ Health; 2013 [Online 7 January 2013]. Published online at:
http://www.ncbi.nlm.nih.gov/pubmed/23289875.
\12\ Anderson GB, et al., Heat-related emergency hospitalizations
for respiratory diseases in the Medicare population. AJRCCM [In Press]
Published on 14 March 2013 as doi: 10.1164/rrcm.201211-1969OC.
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______
Prepared Statement of Stephen I. Katz, M.D., Ph.D., Director, National
Institute of Arthritis and Musculoskeletal and Skin Diseases
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of Arthritis
and Musculoskeletal and Skin Diseases (NIAMS) of the National
Institutes of Health (NIH). The fiscal year 2014 NIAMS budget of
$540,993,000 includes an increase of $6,202,000 over the comparable
fiscal year 2012 level of $534,791,000.
INTRODUCTION
As the primary Federal agency for supporting medical research on
diseases of the bones, joints, muscles, and skin, NIAMS touches the
lives of nearly every American. The burden of these diseases is
substantial. Arthritis limits the activities of nearly 21 million
adults in the United States each year; medical care and lost wages
attributable to musculoskeletal conditions cost Americans an estimated
$950 billion annually; and skin conditions such as eczema and psoriasis
affect more than 12 percent of people world-wide.\1\ NIAMS is
accomplishing its mission of improving health by supporting basic and
translational research that will impact clinical practice, by training
the next generation of bone, joint, muscle, and skin scientists, and by
disseminating the findings from its studies, and related health
information, to all Americans.
BASIC SCIENCE: THE FOUNDATION FOR TOMORROW
Tomorrow's treatments are rooted in the basic research conducted
today. NIAMS is committed to better understanding the molecular and
cellular processes that contribute to health and disease. This basic
research will serve as the foundation for new diagnostic tests,
therapies, and prevention strategies that will improve the lives of
those who are affected by arthritis, and musculoskeletal and skin
conditions.
NIAMS investigators are leveraging the Nation's investment in
understanding the human genome and making use of its associated
technologies. One such project is studying facioscapulohumeral muscular
dystrophy (FSHD)--a neuromuscular disease of the face, shoulders, and
upper arms. Building on earlier findings about DNA sequences on
chromosome 4 that lead to FSHD, researchers discovered that a rare form
of the disease--called FSHD2--is caused by mutations on both chromosome
4 and chromosome 18. These results set the stage for new diagnostic
tests and treatments for patients who have FSHD2. Moreover, the
recognition that distant genes interact with each other may lead to
similar discoveries in other conditions.
NIAMS recognizes industry's important role in conducting basic
research, developing new technologies, and commercializing federally
supported discoveries. For this reason, NIAMS is offering grants to
eligible small businesses for development of biomarkers or therapies
for rare musculoskeletal, rheumatic, or skin diseases.
TRANSLATIONAL SCIENCE: BRIDGING BENCH AND BEDSIDE
NIAMS basic research can only improve public health when the
understanding it generates is translated into new and improved
treatments and preventive strategies. Recent insights into the
molecular mechanisms of cell processes are already suggesting
treatments. NIAMS researchers at the NIH Clinical Center launched a
small clinical trial after experiments into the cause of neonatal-onset
multisystem inflammatory disease (NOMID) revealed that it may be
corrected with the adult rheumatoid arthritis (RA) drug anakinra. The
children participating in the trial, who had been ill for years,
improved within days of receiving the drug. Their rashes disappeared,
their eye problems resolved, and their hearing improved or stopped
worsening. The investigators then initiated a 5-year study, which led
to U.S. Food and Drug Administration (FDA) approval of anakinra for
pediatric NOMID patients earlier this year.
NIAMS-funded basic research also contributed to the recent FDA
approval of a new treatment for RA. The drug, tofacitinib, targets a
protein discovered at NIH in 1993. Following many years of
collaboration between NIH and private industry, tofacitinib became the
first drug approved in more than a decade that can be taken as a pill,
rather than an injection, to slow or halt RA joint damage. It provides
an option for adults with moderately to severely active RA who do not
respond well to the standard therapy for the disease--methotrexate.
In addition to helping patients by supporting basic research and
developing new treatments, NIAMS facilitates work that guides
clinicians in the use of existing therapies. NIAMS funding assisted a
national consortium of pediatric rheumatologists establish treatment
recommendations for newly diagnosed juvenile idiopathic arthritis
patients, and for children who develop kidney inflammation due to
lupus. These recommendations are guiding patient care today and can be
integrated into future effectiveness and toxicity studies as therapies
are developed.
Other work may help clinicians predict which scleroderma patients
will respond to the drug mycophenolate mofetile (MMF), one of the
standard therapies for this disorder. A small clinical trial built on
findings about the molecular causes of scleroderma revealed a
connection between gene expression patterns in patients' skin biopsies
and their responses to MMF. If an ongoing study confirms this genetic
biomarker's predictive value, countless patients might be spared
needless exposure to MMF and could begin receiving other drugs before
their disease progresses.
NIAMS-supported research also is contributing to knowledge about
dietary and behavioral changes that can prevent common public health
challenges. Poor nutritional habits increase older Americans' risk of
metabolic acidosis, a condition that occurs when the body produces too
much acid or the kidneys fail to remove excess acid from the blood.
Because bone is a reservoir for alkaline salts (e.g., calcium
phosphate), it can lose minerals and weaken in an effort to maintain a
healthy acid-base balance. Findings from an NIAMS-funded clinical trial
revealed that the dietary supplement potassium citrate improves the
acid-base equilibrium of people's blood, their calcium balance, and
markers of skeletal health. This supports the hypothesis that potassium
citrate can slow or prevent bone loss that occurs with age. If future
studies confirm the results, potassium citrate could become a safe and
easily administered intervention for patients who have, or are at risk
of, osteoporosis and related fractures.
NIAMS research findings are assisting healthcare providers and
patients select among treatment options. Many adults have debilitating
knee pain due to a tear in the meniscus, a cushion-like tissue that
absorbs impact. Although meniscal tears can be treated with physical
therapy or surgery, it was unclear which intervention was best until a
recent paper showed that most patients benefited equally from either
option over time. Those in the physical therapy group improved less
quickly, however, and about one-third resorted to surgery because
physical therapy did not provide adequate relief.
ENSURING A DIVERSE SCIENTIFIC WORKFORCE
NIAMS is committed to developing and retaining a diverse and
collaborative scientific workforce. Planning discussions in fiscal year
2012 that included investigators, health professionals, and patients
identified the transition from mentored research to full independence
as a vulnerable period in clinician-scientists' careers. In fiscal year
2013, NIAMS met with grantees nearing the end of their clinical or
patient-oriented research career development awards to learn about the
challenges they and their peers are facing. NIAMS plans for fiscal year
2014 include a similar effort, with a long-term goal of identifying
ways to better support early-stage investigators' transition to
research independence.
SHARING HEALTH INFORMATION AND RESEARCH PROGRESS
The Internet and other electronic communication platforms have
emerged as valuable tools for disseminating health information. An
increasing number of visitors are accessing the NIAMS Web site from
mobile devices, and current trends indicate that mobile traffic to Web
sites may overtake desktop traffic as soon as 2015. In response, NIAMS
began providing its health information in a mobile device friendly
format in fiscal year 2013. NIAMS will continue to assess and adapt to
new technologies and tools to provide research updates and health
information to the widest possible audience.
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\1\ Cheng YJ, et al. Prevalence of doctor-diagnosed arthritis and
arthritis-attributable activity limitation--United States, 2007-2009.
MMWR 2010;59(39):1261-1265.
U.S. Department of Health and Human Services, Agency for Healthcare
Research and Quality, Medical Expenditures Panel Survey, 1996-2006.
Data analyzed and modeled by Edward H. Yelin, PhD, Institute for Health
Policy Studies, University of California, San Francisco, San Francisco,
CA, as cited in www.boneandjointburden.org/highlights/FactsinBrief.pdf,
accessed March 27, 2013.
Vos T, et al. Years lived with disability (YLDs) for 1160 sequelae
of 289 diseases and injuries 1990-2010: a systematic analysis for the
Global Burden of Disease Study 2010. Lancet. 2012 Dec
15;380(9859):2163-96. doi: 10.1016/S0140-6736(12)61729-2.
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______
Prepared Statement of James F. Battey, Jr., M.D., Ph.D., Director,
National Institute on Deafness and Other Communication Disorders
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute on Deafness
and Other Communication Disorders (NIDCD) of the National Institutes of
Health (NIH). The fiscal year 2014 NIDCD budget of $422,936,000
includes an increase of $7,436,000 over the comparable fiscal year 2012
appropriation of $415,500,000.
NIDCD conducts and supports research, and research training in the
normal and disordered processes of hearing, balance, smell, taste,
voice, speech, and language. Our Institute focuses on disorders that
affect the quality of life of millions of Americans in their homes,
workplaces, and communities. The physical, emotional, and economic
impact for individuals living with these disorders is tremendous. NIDCD
continues to make investments to improve our understanding of the
underlying causes of communication disorders, as well as their
treatment and prevention. It is a time of extraordinary promise, and I
am excited to be able to share with you some of NIDCD's ongoing
research and planned activities on communication disorders.
RESEARCHERS RESTORE HEARING IN NOISE-DEAFENED MICE
Our ability to hear relies on sensory hair cells in the inner ear.
The hairs on these specialized cells convert sound vibrations into
electrical signals, which travel to the brain by way of the auditory
nerve. When hair cells are damaged--by disease, injury, or aging--a
person experiences hearing loss, and mammals cannot regenerate these
lost hair cells.
Researchers supported by NIDCD have shown for the first time that a
drug can be used to grow sensory hair cells in the inner ear. They
injected a drug into the cochlea (a spiral shaped organ in the inner
ear that shelters hair cells) of mice made deaf by exposure to loud
noise. The drug blocked a cell-signaling system known to keep stem
cells in the inner ear from turning into hair cells. By blocking that
particular pathway, the drug encouraged cells supporting and
surrounding the hair cells to turn into new hair cells, which led to a
small improvement in the mice's hearing.
This is the first study to show that scientists can use a drug to
restore partial hearing in a mouse with noise-induced hearing loss.
Scientists now hope to develop similar treatments to reverse hearing
loss in humans, especially among the estimated 36 million adult
Americans who report hearing loss.
NOVEL APPROACHES OF INNER EAR REGENERATIVE THERAPIES
Although research to determine ways to regenerate inner ear hair
cells is under way, there remains a lack of potential treatments to
restore lost mammalian hair cell function. Research is needed to
identify and facilitate important molecular switches and regulators
that initiate and sustain mammalian hair cell repair.
NIDCD places a high priority in research that focuses on
regenerative medicine. For example, the Institute is planning a
research initiative for fiscal year 2014 with the goal of developing
hair cell regeneration strategies. NIDCD held a workshop, in September
2011, to identify opportunities to induce regeneration in the inner
ear. As a result of this workshop, NIDCD issued a Funding Opportunity
Announcement to encourage innovative and novel approaches to inner ear
regenerative therapies research. The ultimate goal of the research is
to identify and ``turn on'' important molecular switches and regulators
to enable mammals to regenerate and repair their own inner ear hair
cells. This research may result in therapies that will provide hope of
future treatments for those who have lost hearing due to aging, injury,
or noise exposure, including military veterans returning from active
duty.
Another purpose of the initiative is to attract and support NIH-
defined basic and clinical early-stage investigators (ESIs) to the area
of biological repair of mammalian inner ear hair cells. NIDCD is
especially interested in ESIs who bring new, innovative approaches, and
strategies from scientific fields minimally represented in the NIDCD
portfolio, such as tissue fabrication, biomaterials, and regenerative
medicine. By supporting ESIs from other scientific areas, this
initiative will encourage diversified approaches and an increased
number of investigators focused on regenerative therapies in the inner
ear.
RESEARCHERS IDENTIFY GENE LINKED TO PROGRESSIVE HEARING LOSS FROM NOISE
AND AGING
An international team of scientists funded by NIDCD has identified
the first gene in humans and mouse models that is associated with both
noise-induced and age-related hearing loss. The gene, P2X2, appears to
be crucial for the preservation of life-long normal hearing and for
protection from exposure to loud noise. P2X2 is associated with the
human gene locus DFNA41, a form of hearing loss that typically begins
early in life (around 12-20 years of age), and progresses with age.
High-frequency tinnitus (high-pitched ringing in the ears) often
accompanies hearing loss associated with DFNA41.
The research team discovered that the P2X2 gene mutation found in
DFNA41 results in defects in sensory hair cells in the inner ear, which
eventually lead to ongoing hearing loss. The study establishes, at the
cellular and molecular levels, that the function of this ion channel,
previously known to be involved in sensory signaling of pain, has a
major impact on noise-induced and age-related hearing loss.
These findings demonstrate the importance of genetic approaches to
uncover the underlying mechanisms that contribute to hearing loss,
either as a result of age or chronic exposure to noise. Importantly,
identifying the P2X2 mutation may provide scientists with a way to
develop targeted treatments for progressing hearing loss in humans with
DFNA41, and may be applicable to the treatment of noise-induced and
age-related hearing loss in the broader population.
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
SUPPORTS RESEARCH TO DEVELOP A VACCINE AGAINST AN EMERGING TYPE OF
CHILDHOOD EAR INFECTION
Ear infections during childhood are of great concern to NIDCD,
because they not only cause pain and suffering, but they also interfere
with a child's ability to hear properly during a critical period of
language development. Since 2000, childhood vaccines have prevented
many ear infections caused by two strains of bacteria--``Haemophilus
influenzae and pneumococcus''. However, doctors are now seeing an
increase in the number of ear infections caused by another strain of
bacteria, called ``Moraxella catarrhalis (M. catarrhalis)''.
NIDCD-supported scientists are working to understand how this
bacterium infects humans and avoids destruction by the immune system.
They hope to identify a particular structure (called an antigen) that
is very similar among all strains of ``M. catarrhalis'', so that a
vaccine based on a single antigen will protect against as many strains
of the bacterium as possible.
The research team is using bioinformatics to predict which ``M.
catarrhalis'' proteins are likely to be found on the surface, to make
an attractive antigen target. They are using gene chips to identify
which genes are identical or similar among multiple strains of the
bacterium, and then testing these in petri dishes and in animal models.
The scientists are now testing several promising vaccine antigens
against ``M. catarrhalis'', and hope that a new vaccine could be ready
for human testing in a few years.
______
Prepared Statement of Nora D. Volkow, M.D., Director, National
Institute on Drug Abuse
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute on Drug Abuse
(NIDA) of the National Institutes of Health (NIH). The fiscal year 2014
budget of $1,071,612,000 includes an increase of $20,202,000 over the
comparable fiscal year 2012 level of $1,051,410,000.
The individual and societal impact of both licit and illicit
substance abuse in America is incalculable, not to mention the
associated economic cost, estimated at well over half a trillion
dollars a year in healthcare, crime-related, and productivity losses.
The current landscape of the problem reveals both new and recurrent
trends. Prescription drug abuse remains at high levels in all age
groups, causing thousands of needless overdose deaths each year. New
synthetic drugs, like ``bath salts'' and synthetic marijuana
(``spice''), are sending many teens and young adults to emergency
rooms. And as cultural changes promote greater acceptance of the use of
marijuana, more teens report using it and fewer perceive its real
risks. This, despite new research showing that early onset of marijuana
use can disrupt learning circuitry and lower IQ.
NIDA supports a broad research agenda that leverages the full
potential of genetic/epigenetic, psychosocial, neuroimaging,
pharmacological, health services, and epidemiological studies in order
to reduce the burden of drug abuse and addiction. In the context of the
current prescription drug abuse epidemic, for example, NIDA is
harnessing the translational power of a multidisciplinary addiction
science to: (1) identify the major factors that modulate risk; (2)
develop universal, broad-based prevention and treatment models
involving individuals, their families, schools, and communities; (3)
develop pain medications with little or no abuse potential (for
example, a new opioid medication that must pass through the digestive
system to become active, preventing its abuse via non-oral routes); and
(4) promoting physician education to both improve pain treatment and
minimize drug abuse. NIDA also supports research to make the most of
new opportunities and therapeutics, including healthcare reform
legislation that stands to extend effective interventions to under-
served populations, including people with substance use disorders.
NOVEL THERAPEUTICS
To help those already suffering from addiction, we must expand our
treatment toolkit. NIDA is optimally positioned to parlay research
findings into new medication targets and promising compounds for
pharmaceutical company investment or partnerships. Strategies now being
tested include recruiting the body's immune system to attack and
destroy drug molecules before they can enter the brain. This is being
tried against nicotine, heroin, and stimulant drugs such as cocaine and
methamphetamine, for which no medications are yet available. A related
strategy involves delivery of an enzyme that has been molecularly
engineered to rapidly destroy cocaine in the blood, currently in a
phase II clinical trial. Combining existing medications is another
promising approach, which has proven successful for a number of
diseases (e.g., cancer and HIV/AIDS) but has not been exploited for
treating addictive disorders. NIDA also continues to use its National
Drug Abuse Treatment Clinical Trials Network (CTN) as a community-based
platform to test new therapeutic interventions. For example, the CTN is
testing an FDA-approved anxiety medication, buspirone, for its safety
and efficacy in preventing relapse to cocaine use.
WIDENING THE SCOPE OF CARE
Even effective interventions are not useful if they fail to reach
the people who need them. Implementation research and inclusiveness of
diverse populations in clinical trials are thus vital components of
NIDA's research agenda to close the vast treatment gap. One example is
research that pertains to the integration of substance abuse screening,
brief intervention, and referral to treatment (SBIRT) into routine
medical care and evaluation of the impact of such an approach in
clinical outcomes of patients. Importantly, our goals in this context
dovetail those of the Affordable Care Act, which promises to expand the
scope of care and treat more patients suffering from substance use
disorders. Another critical setting is the criminal justice system,
where NIDA has long supported research to better deliver evidence-based
treatment. Now, this focus extends to youth in the juvenile justice
system, virtually all of whom could benefit from prevention or
treatment interventions for drug abuse.
Improving drug abuse prevention and treatment services also helps
ameliorate other health consequences of abuse, including infectious
diseases like HIV and hepatitis C virus (HCV) that can readily spread
through the sharing of needles and other injection drug use equipment.
One of the many translational initiatives spearheaded by NIDA is the
``Seek, Test, and Treat'' (and ``Retain'') strategy, aimed at
evaluating the impact of expanding highly active antiretroviral therapy
(HAART) coverage in criminal justice and other at-risk populations
through aggressive outreach, early entry into HIV treatment, and
follow-up in the community. There is accumulating evidence that early
treatment with HAART reduces new HIV diagnoses, deaths, and HIV
prevalence, suggesting that ``Treatment as Prevention'' should be
implemented as soon and as widely as possible.
NEW SCIENTIFIC OPPORTUNITIES
By taking full advantage of continuous developments in a wide range
of scientific disciplines, NIDA is positioned to make significant
advances in averting and treating addictive disorders. For example, we
can now affordably sequence full individual genomes to identify rare
genetic variations that influence addiction and responses to treatment,
increasing not just our basic understanding of addiction but also
paving the way for personalized treatments. Through the rapidly
developing field of ``epigenetics'', we can determine the lasting
impact of environmental variables like early stress or drug exposure on
gene expression linked to later drug use. Another powerful new tool
called ``optogenetics'', which allows us to activate (or deactivate)
specific brain cells and networks, has enabled NIDA researchers to link
compulsive cocaine-seeking in rats to deficits in the prefrontal cortex
that were reversed by activating the affected brain regions. Clinical
trials will soon test whether noninvasive (magnetic) stimulation can
modify brain activity and reduce compulsive drug-seeking and craving in
human drug users. Meanwhile, advanced imaging techniques are allowing
us to ask questions about brain structure and function that were
unimaginable just a few years back.
Yet even with these new technologies, the underlying causes of most
neurological and psychiatric conditions remain poorly understood, due
to the human brain's incredible complexity. NIDA is one of the key
participants in an exciting new NIH initiative to conquer this major
frontier. Brain Research through Advancing Innovative
Neurotechnologies, or BRAIN, will produce a revolutionary new dynamic
picture of the brain, showing how individual cells and complex neural
circuits interact in healthy individuals, and in those with brain
disorders.
To better capitalize on synergies in addiction science, NIDA, the
National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the
National Cancer Institute (NCI) have formed a consortium, the
Collaborative Research on Addiction at NIH (CRAN), which will pool
resources and expertise to address unmet research opportunities and
public health needs. Among these, the study of ``comorbidities'' is
poised to benefit. NIDA, NIAAA, and the National Center for
Complementary and Alternative Medicine, in collaboration with the
Department of Defense, recently issued a call for research on
interventions to prevent comorbid alcohol and other drug abuse in U.S.
military personnel, veterans, and their families. NIAAA and NIDA also
issued a call for research on mechanisms of alcohol and nicotine co-
addiction.
The accelerating pace of science is rapidly outstripping our
capacity to use what we collect. ``Big Data'' requires a significant
repositioning in who we train and how we can best identify and exploit
emerging scientific opportunities. We will need to build a workforce
that includes people skilled in non-biomedical fields, such as
informatics, computational science, mathematics, and engineering.
Training the next generation of scientists to be able to understand the
possibilities and complexities of what they will be dealing with is a
daunting but exciting challenge as we go forward.
In closing, we know much more about the causes and treatment of
substance use disorders than ever before. Yet obstacles such as the
lingering stigma attached to diseases of addiction continue to hamper
our ability to recognize and care for those afflicted. NIDA remains
committed to tackle these and other challenges, taking advantage of
unprecedented scientific opportunities to transform how we prevent and
treat substance abuse and related health consequences in this country.
______
Prepared Statement of Kenneth R. Warren, Ph.D., Acting Director,
National Institute on Alcohol Abuse and Alcoholism
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute on Alcohol
Abuse and Alcoholism (NIAAA) of the National Institutes of Health
(NIH). The fiscal year 2014 NIAAA budget request of $463,848,000
reflects an increase of $5,183,000 over the comparable fiscal year 2012
level of $458,665,000.
SCOPE OF THE PROBLEM
According to the Centers for Disease Control and Prevention,
excessive alcohol use cost the U.S. an estimated $223.5 billion in
2006; it also takes a tremendous toll on individuals and their
families. Alcohol affects individuals across the lifespan, from the
developing fetus to the elderly. Each of you likely knows someone
affected by alcohol problems.
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM RESEARCH
To reduce the considerable burden of illness associated with
alcohol misuse, NIAAA is working to prevent the onset and escalation of
drinking during childhood and adolescence and intervene with problem
alcohol use at all ages. A substantial portion of NIAAA's research
portfolio focuses on the underlying mechanisms, prevention, and
treatment of alcohol dependence. The remainder is allocated to studies
on the consequences of alcohol use, including: health benefits
associated with moderate drinking; adverse effects resulting from
alcohol misuse such as fetal alcohol spectrum disorders (FASD), effects
on the developing adolescent brain, and tissue and organ damage; and
policy research to reduce harms both to drinkers and those around them.
FUNCTIONAL INTEGRATION
NIAAA has embraced the decision of the NIH Director to pursue a
functional integration of addictions research, which provides a
framework for NIAAA, the National Institute on Drug Abuse (NIDA), the
National Cancer Institute (NCI), as well as other Institutes and
Centers (ICs), to enhance and expand collaborations and identify
synergistic research opportunities to advance addictions science. Now
referred to as the Collaborative Research on Addictions at NIH (CRAN),
this new venture will support a variety of activities. Importantly,
while advancing addictions research, a functional integration maintains
the unique research contributions of each IC.
Prior to the official launch of CRAN, NIAAA, and NIDA implemented a
number of changes to improve integration between the two ICs and
initiated additional joint funding opportunity announcements (FOA). One
joint FOA focuses on research to prevent alcohol and other drug abuse
in active military personnel, veterans and their families. Going
forward, CRAN will explore cross-cutting research opportunities such as
studies on individuals who suffer from addiction to multiple
substances--40 percent of individuals who have a past year addiction to
illicit drugs and/or abuse prescription drugs also have past year
alcohol abuse or dependence, and 16 percent of individuals with past
year alcohol abuse or dependence have a past year drug addiction. CRAN
will also support efforts to identify mechanisms that underlie tobacco,
alcohol and/or other drug addiction, recognizing that while some
mechanisms may be common to more than one substance, others will be
unique. Expanding studies to address multiple substances when feasible
and appropriate will enhance our ability to treat multi-substance co-
morbidities in an efficient and cost-effective manner. Funding
opportunities under CRAN will begin in fiscal year 2014 with two
initiatives; the first will expand existing projects to be more
integrative and/or collaborative, the second will focus on mobile
technologies and social media for interventions for substance abuse.
NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM'S UNIQUE RESEARCH
FOCUS
NIAAA also has a robust research program outside of CRAN. Studies
exploring pharmacological, behavioral and policy interventions to
reduce acute and chronic consequences of alcohol misuse are a major
component of NIAAA's portfolio. Medications development is an active
area of study, both for the treatment of alcohol dependence and for the
treatment of consequences of chronic alcohol misuse such as alcohol-
induced liver disease. NIAAA's Clinical Investigations Group (NCIG) has
streamlined the process for phase 2 clinical testing of potential
compounds for alcohol dependence and has established an active
collaboration with pharmaceutical companies. In a recent NCIG-led
study, the smoking-cessation medication varenicline (Chantix)
significantly reduced alcohol consumption and craving among people who
are alcohol-dependent. Varenicline's effects were comparable to those
seen in studies of naltrexone and acamprosate, two of the medications
already approved by the U.S. Food and Drug Administration (FDA) for the
treatment of alcohol dependence. If varenicline receives FDA approval
for treatment of alcohol dependence, it could significantly expand
treatment options. Personalizing treatment also continues to be a goal,
and studies showing links between an individual's genetic make-up and
treatment efficacy for various medications suggest that goal is within
reach. Relapse, however, is still common and a focus of NIAAA research.
A recent study showed that distinct patterns of brain activity are
linked to a higher rate of relapse among patients in early recovery.
These patterns may be useful for identifying patients at greatest risk
for relapse.
The link between stress and alcohol-related problems is an
important area of investigation. While a number of studies have focused
on how stress contributes to the development of alcohol-related
problems and relapse, a recent line of investigation is exploring how
chronic alcohol use might increase vulnerability of the brain to the
development of stress-related disorders. A study in mice suggests that
chronic alcohol use may increase the risk for post-traumatic stress
disorder (PTSD) by altering neural circuits that normally enable the
brain to extinguish fear following a traumatic event.
NIAAA also continues to support medications development for the
treatment of alcoholic liver disease (ALD), one of the most serious
medical consequences of alcohol dependence, and continues to seek
biomarkers for alcoholic liver damage. Scientists are gaining an
appreciation for the interconnectedness of systems within the human
body. NIAAA uses a systems biology approach to investigate how
pathological changes in one organ as a result of alcohol exposure can
also result in physiological aberrations in another. Basic research
using animal models is also important to better understand the
mechanisms underlying ALD; however, many of the current models do not
evoke the full range of symptoms or are expensive and technically
difficult. A new mouse model of alcohol drinking and disease was
developed which more closely approximates ALD in humans and may also be
useful to study alcohol damage of other organs.
The developing embryo/fetus is uniquely vulnerable to the effects
of alcohol; prenatal alcohol exposure is a significant contributor to
neurodevelopmental disorders in children. Understanding the mechanisms
leading to the neurodegeneration that underlies development of FASD is
a critical step in developing treatments. A recent study provides
evidence that endocannabinoids and their receptors in the brain play a
role in the development of FASD.
Policy research is another important component of NIAAA's
portfolio. Data from NIAAA-supported studies will help inform local
decisions such as the implementation of policy measures on college
campuses to reduce alcohol poisonings. In addition, research findings
play an important role in national issues such as the debate over the
legal limit for blood alcohol content for operation of a motor vehicle,
as policy-makers work to find a balance between increased alcohol
restrictions and public safety. Screening and brief intervention for
harmful alcohol use have been a major focus of NIAAA research for
several decades. Based on this research, the U.S. Preventive Services
Task Force (USPSTF) recently recommended that clinicians screen adults
for alcohol misuse and provide persons engaged in risky or hazardous
drinking with brief interventions. The USPSTF did not endorse screening
for adolescents citing insufficient evidence. To increase this evidence
base, NIAAA is supporting six studies to evaluate its youth alcohol
screening guide in a variety of settings as a predictor of alcohol
risk, alcohol use, and alcohol problems, and as an initial screen for
other behavioral health problems such as drug use or smoking.
In summary, NIAAA is enthusiastic about opportunities to expand
research to improve the lives of Americans struggling with addiction to
alcohol and other substances through the newly created CRAN. At the
same time, NIAAA continues to focus on reducing the significant burden
of illness associated with alcohol misuse.
______
Prepared Statement of Patricia A. Grady, Ph.D., RN, FAAN, Director,
National Institute of Nursing Research
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of Nursing
Research (NINR) of the National Institutes of Health (NIH). The fiscal
year 2014 NINR budget of $146,244,000 includes an increase of
$1,744,000 over the comparable fiscal year 2012 level of $144,500,000.
The mission of NINR is to promote and improve the health of
individuals, families, communities, and populations. The Institute does
so by supporting and conducting clinical and basic research to build
the scientific foundation for clinical practice, prevent disease and
disability, manage and eliminate symptoms of illness, improve
palliative and end of life care, and train the next generation of nurse
scientists. NINR-supported investigators contribute to developing the
evidence base for science-driven practice through innovative treatment
and behavioral research. Today, I offer a brief overview of NINR's
investment and progress in six key areas and provide examples of how
the research we support improves quality of life.
SYMPTOM MANAGEMENT IN MULTIPLE CHRONIC CONDITIONS
Due to the large aging population with longer life expectancies,
and treatment advances for formerly fatal diseases, over one in four
Americans are living with multiple chronic conditions (MCC) and their
associated adverse symptoms. To address these symptoms and improve
quality of life, NINR currently supports five Centers of Excellence in
symptom science that explore pain, sleep disturbance, and the effects
of chronic illness on neurocognitive functioning. A recent NINR-
supported study found an association between an anti-inflammatory
protein and a symptom cluster, including pain, fatigue, and sleep
disturbance, opening the door to potential therapeutics development to
alleviate these symptoms.
FAMILY AND COMMUNITY-BASED RESEARCH
The family and community-based approach to clinical and
translational research is intrinsic to nursing science and NINR. Child
behavioral issues can create problems that negatively affect learning
and peer relationships. NINR-supported studies that developed and
tested the Chicago Parent Program (CPP), a high-quality, cost-
effective, early childcare program for low-income communities that
promotes positive parenting behaviors and reduces risky behaviors in
children and their families. The CPP was adapted and disseminated to
Chicago Head Start sites, where it was well-received in the community.
The researchers reported improvements in parenting skills and child
behavior. Based on these results, CPP-derived interventions have been
implemented in diverse settings across the U.S., such as the Mayo
Clinic, the Harlem Children's Zone, Johns Hopkins Bayview Medical
Center, and New York City and Chicago Head Start centers. CPP's
successful adoption into diverse communities underscores the importance
of partnering with individuals, families, communities, and healthcare
practitioners to ensure a program's effective translation into real
world settings.
PALLIATIVE CARE AND END OF LIFE RESEARCH
As the lead NIH Institute for end-of-life research, NINR supports
evidence-based palliative care research that assists individuals,
families, and healthcare professionals in managing the symptoms of
advanced illness and planning for end-of-life decisions. Individuals of
all ages with advanced illness can face protracted courses of decline,
requiring that difficult decisions be made to ensure appropriate
intervention and to maximize quality of life. NINR supports a
palliative care research cooperative to enhance the evidence base for
palliative care by carrying out multi-site research studies and
clinical trials to be used to inform health practice and policy.
NINR grantees are also evaluating palliative care interventions for
patients with heart failure. Others are testing the efficacy of an
integrated model of palliative care early in the cancer diagnosis
process. The Institute also supports research on family members'
perceptions and the importance of end-of-life strategies. These
activities will provide for both optimal care and treatment for
patients facing life-limiting conditions, and assist patients and
family members.
RESEARCH TO IMPROVE CLINICAL PRACTICE
As the healthcare providers most frequently interacting with
patients, nurses are uniquely positioned to develop successful
interventions to address treatment challenges. As our Nation's aging
population continues to grow, the demand for critical care services is
projected to increase. As a result, the number of patients transferred
to long-term acute care hospitals, and the resulting costs, are
expected to increase significantly. A recent NINR-funded study compared
two methods for weaning patients from prolonged mechanical ventilation.
Researchers found that one method, using a device known as a
tracheostomy collar, resulted in earlier, successful weaning from
mechanical ventilation. Implementing standard, best practice guidelines
based on these findings could lead to shorter length of stays, better
patient outcomes, and decreased healthcare costs. NINR will continue to
facilitate the implementation of evidence-based treatment interventions
into the clinical setting.
INNOVATIVE TECHNOLOGIES TO ENHANCE HEALTHCARE
Innovative technologies are gaining a larger role in healthcare,
and nursing science can provide the foundation for developing novel
advances that deliver personalized care and real-time information to
individuals, families, and communities. For example, subtle changes in
an individual's health status often indicate the early development of
acute illness or worsening of chronic conditions, but detecting these
changes can be difficult. NINR supported the development of an
unobtrusive, inexpensive proactive disease management system that uses
infrared sensors to monitor older adults' daily activities and
automatically alert healthcare providers to changes in the patient's
health status. This technology identified health conditions 1-2 weeks
earlier than traditional assessment methods and led to improved
functional abilities. Based on these successful results, the
researchers hope to expand its use to other care facilities.
For example, NINR supports scientists who are using information
technology (IT) to assist patients in understanding the medications
they are supposed to take and track whether they are actually taking
the medications as prescribed. These scientists are developing an
Electronic Medical Record (EMR)-based tool (the Medtable), which is now
being evaluated for its effectiveness in provider/patient communication
and whether it improves medication knowledge, adherence, and health
outcomes among chronically ill adults with complex medication regimens.
LOOKING TOWARD THE FUTURE: NURSE SCIENTISTS
This Nation is facing complex healthcare challenges, and nurses and
nurse scientists will play a pivotal role in addressing these issues.
Since its inception, the training and career development of an
innovative and diverse scientific workforce have been fundamental to
NINR's mission. NINR supports nurse scientists and promotes earlier
entry of nurses into research by providing research fellowships and
career development awards. A recent initiative, the Scholars Training
for the Advancement of Research (STAR) program, provides additional
resources for institutions to support the ``fast-track'' training of
outstanding undergraduate nursing students who are interested in
pursuing a Ph.D. NINR training programs produce future nursing school
faculty to strengthen the nursing workforce.
In closing, NINR appreciates the opportunity to support science
that can significantly improve the health of the Nation. The Institute
provides innovative nursing science that becomes the evidence-based
practice for clinical care. NINR will continue its mission to improve
the quality of life by advancing nursing science to shape the future
direction of healthcare.
______
Prepared Statement of Eric D. Green, M.D., Ph.D., Director, National
Human Genome Research Institute
Mr. Chairman and members of the committee: I am pleased to present
the fiscal year 2014 President's budget request for the National Human
Genome Research Institute (NHGRI). The fiscal year 2014 budget of
$517,319,000 includes an increase of $5,061,000 above the comparable
fiscal year 2012 level of $512,258,000.
THE LAST DECADE OF GENOMICS HAS CHANGED BIOMEDICAL SCIENCE
This year, we celebrate the tenth anniversary of the completion of
the Human Genome Project (HGP). An ambitious scientific endeavor
likened to biology's ``moon shot,'' HGP catalyzed profound changes for
many areas of biomedical research and beyond. To provide a perspective
about these changes, it is illustrative to compare the ``state-of-the-
art'' at the beginning of HGP in 1990, at its completion in 2003, and
now. To place these three-time points in a cultural context, in 1990
Americans communicated by phone and fax; in 2003 it was email; and in
2013 it is the tweet.
Just as technology development has transformed routine
communications (from the phone call to the tweet), it has been the
cornerstone of the Federal investment in genomics. During the HGP, it
took 6-8 years of active sequencing and approximately $1 billion to
generate that first sequence of the human genome. In 2003, that same
feat would have required 3-4 months and $10-50 million. Today, a human
genome can be sequenced in approximately 1-2 days for a mere $3-5
thousand. As the time and cost have plummeted, the power of genomic
strategies to advance research and the volume of generated genomic data
have increased profoundly.
Why is this massive increase in capacity for data generation
important? This extraordinary increase in data generation allows us to
understand genome structure and function and through this knowledge to
learn how genomes contribute to health and disease. For example, in
1990, we knew of approximately 50 genes that, when mutated, caused a
human disease; in 2003 that number was almost 1,500; and today, it is
nearly 3,000. Further, knowledge about the genomic basis for our
responses to medications--an area of science called pharmacogenomics--
has also grown steadily. In 1990, only four Food and Drug
Administration (FDA)-approved drugs required labels that pointed out
the relevance of a patient's genetic makeup for that medication; by
2003, this number had increased to 46; and today, it stands at 106. In
fact, genomic contributions to medical research have been so
substantial that fully half of the 2012 ``Top 10 Medical
Breakthroughs'' identified by ``Time Magazine'' \1\ reflected genomics
accomplishments, and these were in large part supported and/or
facilitated by NHGRI's research programs.
Although extraordinary progress has occurred over the past decade,
much remains to be learned about the genome's role in biology and
disease, and how to translate that knowledge to improve health
outcomes. At the conclusion of HGP, we were but at the beginning of an
exciting, but long journey to learn how to apply genomic information to
improve health.
LEARNING FROM THE DATA DELUGE
A major challenge for genomics research is the handling, analysis,
and interpretation of the large volumes of genomic data now routinely
generated. Solving this will require innovative infrastructure and
novel methodologies. In fiscal year 2014, NHGRI will support pioneering
bioinformatics research across its research portfolio, from the use of
cloud computing for efforts such as the 1000 Genomes Project to the
development of novel clinical bioinformatics tools by the Clinical
Sequencing Exploratory Research (CSER) program and the Electronic
Medical Records and Genomics (eMERGE) Network, two flagship programs
intended to study how to utilize an individual's genomic information in
different clinical settings. Additionally, the Institute will provide
key leadership within NIH for the Big Data to Knowledge (BD2K)
initiative.
Consistent with NHGRI's 2011 strategic plan, the Institute's
portfolio spans a continuum from basic research to study genomic
structure and function, to translational research to discover the
genomic basis for disease, through efforts to use genomics to increase
the effectiveness of healthcare. The ENCyclopedia of DNA Elements
(ENCODE) project, a key effort to identify the `functional parts'
within the human genome, published a landmark series of papers in 2012
reporting a catalog of functional elements within the human genome. The
ENCODE catalog is like a GPS map for the human genome--just as by
zooming in on a GPS map of the United States (to find the location of
points of interests like banks and gas stations), the ENCODE catalog is
now routinely used by researchers worldwide to zoom in on regions of
interest in the human genome that are important for their studies. In
fiscal year 2014, NHGRI will begin to add another layer of knowledge to
this map with the launch of the Genomics of Gene Regulation (GGR)
initiative. GGR will fund research to decipher how genes are regulated
and to understand how gene regulation affects the function of cells and
tissues, human development, and disease.
In fiscal year 2014, NHGRI also will continue advancing the
discovery of the genomic bases of disease. For example, the search for
genes that play a role in rare diseases will be accelerated through the
work of NHGRI's Centers for Mendelian Genomics, as well as an
extramural expansion of the highly successful NIH Undiagnosed Diseases
Program. Through research programs such as the Large-Scale Genome
Sequencing and Analysis Centers, the genomic underpinnings of common
complex diseases, such as cancer, diabetes, autism, and Alzheimer's
disease, will remain a focus within NHGRI's portfolio as well.
IMPLEMENTING GENOMIC MEDICINE
With the increasing accessibility of genomic technologies, the
utility of genomics is already being demonstrated in clinical areas
such as pharmacogenomics, non-invasive prenatal testing, infectious
disease diagnostics, and cancer. The largest class of drugs now with
FDA-required pharmacogenomic information to guide use on their labels
includes those used for the treatment of cancer. Further, genome
sequencing to identify mutations in a tumor's DNA sequence is now
commonplace in the research setting and beginning to be seen in the
clinical setting. Current examples of genomics informing care include
the widespread use of ``BRCA'' testing in patients with familial risk
factors for breast and ovarian cancer, the use of testing to predict
breast cancer recurrence, and the use of genomic diagnostic tests to
determine the suitability of particular treatments such as trastuzumab
(Herceptin) use in breast cancer, vemurafenib (Zelboraf) use in
melanoma, or crizotinib (Xalkori) use in lung cancer.
In fiscal year 2014, NHGRI also will continue extending its
portfolio to investigate the methods and evidence needed to integrate
genomics as a standard component of clinical care. Both existing (e.g.,
CSER program) and new (e.g., Genomic Medicine Pilot Demonstration
projects and the Genomic Sequencing and Newborn Screening Disorders
program) initiatives will be carried out by integrated research teams
that include clinicians, scientists, and bioethicists. These multi-
disciplinary groups will examine the medical as well as the ethical,
social, and legal issues involved with making genomic data an
essential, broadly accessible and broadly desirable element to inform
clinical care. In fiscal year 2014, the Institute will continue
supporting research pertaining to the pursuit of genomic research and
the realization of genomic medicine, including protecting research
participant privacy, determining when to return individual results, and
how to handle unanticipated, but clinically important, ``incidental
findings''.
Through these and other programs, NHGRI will continue to lead the
field of genomics in an effort to benefit the broad biomedical research
enterprise and to realize the goal of advancing human health through
genomics research.
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\1\ http://healthland.time.com/2012/12/04/top-10-health-lists/
slide/junk-no-more/.
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______
Prepared Statement of Roderic I. Pettigrew, M.D., Ph.D., Director,
National Institute of Biomedical Imaging and Bioengineering
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Institute of Biomedical
Imaging and Bioengineering (NIBIB) of the National Institutes of Health
(NIH). The fiscal year 2014 NIBIB budget request of $338,892,000 is
$1,164,000 more than the comparable fiscal year 2012 level of
$337,728,000. The mission of NIBIB is to improve human health by
leading the development and accelerating the application of biomedical
technologies. The Institute is committed to integrating the engineering
and physical sciences with the life sciences to advance basic research
and medical care. As we enter our second decade as an NIH Institute,
NIBIB is continuing to build on that integration.
From wound healing to finding ways for the human body to create new
cartilage for damaged joints, advances in regenerative medicine are
helping wounded warriors and an aging population. Robotic leg
prostheses with powered knee and ankle joints and other efforts in
rehabilitation engineering hold the promise of giving once unimaginable
independence to people who are severely paralyzed or have lost limbs.
Advances in the field of nanotechnology, such as the ability to deliver
drugs directly into tumors while sparing healthy tissue, and using
imaging technologies for non-invasive treatment as well as diagnostics,
hold the potential to make healthcare more precise and more effective
for patients.
ADVANCES IN REGENERATIVE MEDICINE
NIBIB is at the forefront of the developing field of tissue
engineering and regenerative medicine, and already advances in stem
cell research are being developed to aid our wounded warriors and the
general population. Working toward this goal is the Armed Forces
Institute for Regenerative Medicine (AFIRM), which includes NIBIB-
funded researchers and more than thirty U.S. universities and
companies. Research supported by AFIRM has developed advanced treatment
options and accelerated delivery of regenerative medicine therapies to
treat the most severely injured U.S. service members. An exciting
example of just one of the many innovative projects under way is the
development of bioprinting of skin for battlefield injuries. This
technology uses a bioprinter that creates and delivers skin cells and
biomaterials to rapidly cover large wounds, which are a major cause of
morbidity and mortality in severe burn injuries in civilians and
military personnel. Other efforts are focusing on the difficult repair
of segments of bone and nerve that are lost or damaged following
traumatic injuries.
In the general population, injury to cartilage can lead to joint
pain and arthritis. One regenerative medicine project may help patients
with knee injuries to successfully regenerate new, working cartilage
through an innovative technique developed by NIBIB-funded researchers.
The technique uses an engineered `biogel' scaffold (a structure that
supports and holds cells together) that solidifies when exposed to
light, combined with a strong biological adhesive that covers the
injured area and provides an environment that promotes the growth of
cartilage-producing cells. This successful research led to a small
clinical trial in patients undergoing microfracture surgery, a first-
line therapy for cartilage repair where holes are drilled in the
cartilage to encourage new growth. Patients who received the biogel and
adhesive, in addition to microfracture surgery, had improved cartilage
growth, less scarring, and decreased pain at 6 months post-surgery,
when compared to microfracture without the biogel treatment. The
technique has the potential to transform the field of knee cartilage
repair, which affects many people and is difficult to treat
successfully. A larger clinical trial using this promising technique is
currently in progress. While the clinical trials are not funded by
NIBIB, these are examples of public private partnerships of translating
research to clinical settings.
REHABILITATION ENGINEERING TO ENABLE INDEPENDENCE
Overcoming major barriers, researchers have now developed an
implantable, compact, self-contained device for the sensing and
transmission of brain activity. The device is an important step toward
the development and use of brain-computer interfaces that harness the
power of thought to remotely control computers, prosthetics, and other
devices. The new wireless device allows the user more freedom of
movement than the earlier version, which was connected to a computer
with wires and cables and greatly limited the range of movement. The
small device is fully implanted beneath the skin much like a cochlear
implant. It is capable of recording neural activity from 100 different
sites and converting this neural activity into digital signals. It also
transmits these digital signals to a wireless receiver located some
distance outside the body. The device is recharged wirelessly. Initial
tests in animals were successful at recording data in real-time for
more than a year. The device may one day be used to control prosthetic
arms and other devices, motorized wheelchairs, or for diagnostic
monitoring in disorders such as in epilepsy, where patients currently
are tethered to the bedside during assessment.
ENGINEERING ADVANCED MEDICAL SOLUTIONS
NIBIB continues to support technologies for more efficient and
effective drug delivery. Key developments include the creation of
nanoparticles that can target powerful cancer-killing medications to a
tumor without inadvertently damaging surrounding healthy tissues. In
addition to successfully targeting the tumor, a drug that is tethered
to a nanoparticle can only reach its target if it survives in the
blood, where the immune system is constantly removing foreign
particles. To address this technical hurdle, researchers devised a
stealth coating for nanoparticles that tricks the immune system into
ignoring the particles. By disguising the nanoparticles to chemically
look like ``self'', the immune system does not clear the particles, and
more medication can be delivered to their target tumors. Using this
method, tumors in mice were reduced by 70 percent compared with tumors
that were targeted with the cancer drug but without the nanoparticle
and stealth coating. Based on these encouraging results, human clinical
trials using stealth-coated nanoparticles to deliver anticancer drugs
are currently under way. This technology might one day be used to
deliver genes for gene-therapy treatment or to enhance biocompatibility
and durability of larger foreign objects such as pacemakers and
implants, whose function can degrade over time due to attacks by the
immune system.
NIBIB also supports research that harnesses the power of magnetic
resonance imaging (MRI) and the faster metabolic rates of cancer cells
than normal cells to develop a biomarker for prostate cancer. The goal
is to use the biomarker to distinguish which prostate cancer disease is
aggressive from those that are indolent where watchful waiting may be
the appropriate course of action. Researchers have developed a
technique using hyperpolarized carbon-13 (C-13) compounds to measure
the faster metabolism of glucose in prostate cancer. In this method, by
``hyperpolarizing'' the carbon isotope, investigators are able to
increase the target signal by about 10,000-fold, making this carbon
labeled signal much more readily detectable. The researchers developed
a system for synthesizing, hyperpolarizing, and rapidly delivering
carbon-13-labeled pyruvate, a product of glucose metabolism. The
metabolic changes of pyruvate to lactate serve as a biomarker or
indication for prostate cancer as the disease progresses and provide
useful measures of the aggressiveness of the tumor. Preliminary
clinical results show promise for this approach for cancer biomarkers.
NEW USES OF ULTRASOUND FOR DIAGNOSIS AND TREATMENT
The immune system's natural killer (NK) cells are those that find
and destroy foreign substances in the body. A human NK cell line, NK-92
can be used to target and destroy tumors. However, this promising
strategy to use the immune system to fight tumors is not possible for
use in the brain because NK cells cannot penetrate the blood brain
barrier (BBB). NIBIB-funded researchers developed an experimental
system using ultrasound to deliver NK-92 cells to tumors in the brain.
The movement of the NK cells into the tumor was monitored with and
without focused ultrasound disruption of the BBB. Using MRI,
researchers found that approximately 1 NK cell for every 100 tumor
cells had reached the brain when using focused ultrasound to open the
BBB, compared to 1 NK cell per 1,000 tumor cells when ultrasound was
not used. These preclinical results suggest that the tumor-killing
ability of immune natural killer cells combined with focused ultrasound
has tremendous potential for targeting and destroying brain tumors.
Another new ultrasound imaging technique developed by NIBIB-
supported researchers can noninvasively detect tumors and fibrosis in
the liver. Typically, liver disease is diagnosed using liver biopsy, a
surgical procedure that can be painful and cause complications. This
new ultrasound-based technique, called Acoustic Radiation Force Impulse
imaging does not produce harmful ionizing radiation and is relatively
inexpensive compared with other imaging modalities. This means it can
be used more frequently to track the progression of fibrosis. In
contrast to a biopsy, which can only examine a small discrete sample of
the liver, this method examines the entire liver. The technique uses
focused, high intensity sound waves to produce ``push-pulses'' that
generate shear within tissue. Ultrasound is then also used to monitor
the tissue response. The tissue response is related to the stiffness
properties and structure of the liver, and is displayed as a high
resolution, qualitative image. This technique can also produce
quantitative stiffness measurements based on the speed of the shear
waves. These measurements are used to quantify specific levels of
fibrosis that can be used to classify different stages of liver
fibrosis or tumors.
Yet another advance is the use of the mechanical force of
ultrasound to breakup thrombi and minimize the damage to heart muscle
during a heart attack. Researchers first demonstrated in porcine models
of coronary arteries blocked by blood clots or thrombosis, that
conventional ultrasound using a high ``mechanical index'' in
conjunction with micro-bubbles and a conventional clot dissolving agent
achieved greater restoration of flow in the blocked artery.
Consequently, there was also greater heart muscle salvaged. In an
initial human study, this technique was successfully and safely used in
patients who presented at a hospital with evidence that a heart attack
had begun. If the promise of these preliminary studies continues, this
could be implemented at hospitals throughout the country as a first-
line treatment to minimize damage in evolving heart attacks.
NIBIB will continue to target the unique scientific opportunities
of the 21st century in rehabilitation engineering, regenerative
medicine, and advanced imaging techniques to improve disease diagnosis
and treatment. This era promises a revolution in employing technology
to realize innovations that address healthcare challenges, reduce
disease mortality and morbidity, and enhance quality of life and
improve the health of the Nation.
______
Prepared Statement of Christopher P. Austin, M.D., Director, National
Center for Advancing Translational Sciences
Mr. Chairman and members of the committee: It is a privilege to
present to you the President's budget request for the newly established
National Center for Advancing Translational Sciences (NCATS) for fiscal
year 2014. The fiscal year 2014 budget for NCATS is $665,688,000, which
represents an increase of $91,391,000 over the fiscal year 2012
comparable level of $574,297,000. The request includes $50 million for
the Cures Acceleration Network (CAN), an increase of $40 million over
fiscal year 2012. CAN will fund initiatives designed to address
scientific and technical challenges that impede translational research,
including support for the Tissue Chips for Drug Screening Initiative,
the Discovering New Therapeutic Uses for Existing Molecules Program,
and other programs. Common Fund support of these programs will end by
fiscal year 2014, at which time they will be funded through the NCATS
direct appropriation.
NCATS' mission is to catalyze innovations that enhance the
development, testing, and implementation of diagnostics and
therapeutics across a wide range of human diseases and conditions. In
the short time since its founding in December 2011, NCATS has become a
hub of innovation for translational sciences at NIH and in the broader
translational ecosystem that includes the pharmaceutical,
biotechnology, venture capital, regulatory, and patient advocacy
communities. The Center has launched several major research
initiatives, cultivated promising strategic partnerships, and
established a presence at NIH and in the community. For example, NCATS'
Therapeutics for Rare and Neglected Diseases (TRND) program was
responsible for the development and first-in-human testing of new
therapies for four different diseases in a period of 16 months via
novel partnership structures. Another achievement was the agreement
with the Defense Advanced Research Project Agency and the Food and Drug
Administration (FDA) to initiate an innovative grant program to create
new tools for predicting drug toxicity. The goal is to fund researchers
who will create 3-D ``chips,'' which are miniature models with the
structure and function of human organs. These chips will be used to
test drugs to see if they are safe or toxic to humans, thus saving
researchers time and money compared to current methods. NCATS also
developed the New Therapeutics Uses for Existing Molecules initiative,
a breakthrough partnership program with eight pharmaceutical companies
to find new uses for existing drugs owned by these companies. The eight
companies agreed to make many of their molecular compounds available to
outside researchers for testing for new therapies. These compounds have
already undergone safety and toxicity testing in humans and so provide
researchers with valuable data that may help speed the research process
forward. In addition, NCATS has created template agreements with the
drug companies ready for use by the investigator, thus saving the time
the investigator would have spent negotiating an agreement with the
drug company.
Collaborations among Government, academia, industry and nonprofit
patient organizations are crucial for successful translation. For
example, support from the NCATS' Clinical and Translational Science
Award (CTSA) program at the University of Pittsburgh contributed to the
development of a robotic arm that allowed a quadriplegic patient to
feed herself using just her thoughts. This remarkable achievement was
the result of NIH, the Department of Defense, the Department of
Veterans Affairs (VA), the FDA, a private foundation, two academic
research centers, and a private company working together, which made
this possible.
AVOIDING DUPLICATION, REDUNDANCY AND COMPETITION
A fundamental principle of NCATS is that it addresses the many
translational problems that are not undertaken by industry because this
early-stage research hasn't yet proven to be commercially viable. Thus,
NCATS is explicitly complementary to efforts in industry. Our work is
in the ``precompetitive'' space where industry and NIH/academia have
long collaborated to mutual benefit.
In addition to this general positioning of NCATS as an ``adaptor''
or ``intermediary'' between academic and industry science, many
specific initiatives have been put in place to prevent duplication,
redundancy, and competition with industry. We recently published a
Notice in the Federal Register that enumerates and seeks comments on
the procedures and methods NCATS is using to ensure that industry is
both aware of and able to provide input on our activities and planned
initiatives. Some of these methods include frequent updates to the
NCATS Web site, an NCATS Director's newsletter, publication of Requests
for Information on proposed programs, open public meetings to which
industry representatives are specifically invited, and meetings
arranged with industry trade groups and associations.
PRE-CLINICAL RESEARCH: CONNECTING LABORATORY POTENTIAL WITH CLINICAL
PROMISE
NCATS is active in the development, demonstration, and
dissemination of a broad range of technologies, tools, and resources
that facilitate collaborative pre-clinical testing and first-in-human
clinical trial implementation. For example, NCATS' Matrix Screening
``Platform,'' or testing process that includes specific equipment, is a
transformative technology that identifies combinations of drugs to
treat diseases resistant to single drugs, which is particularly
important for treatment-resistant cancers. Since this testing is done
in a high-speed fully automated robotic format, thousands of drug
combinations can be tested in a single day to determine which are best
able to kill the cancer cells while minimizing toxic side effects.
Determining toxicity is a major roadblock in the advancement of
promising discoveries. The Tox21 Program, along with the Environmental
Protection Agency, the National Institute for Environmental Health
Sciences, and the FDA, is testing over 10,000 drugs and environmental
chemicals for hundreds of activities relevant to toxicity, with all
data being made publicly available.
CLINICAL RESEARCH: DEMONSTRATING MEDICAL BENEFIT
Clinical research is conducted to test the safety and effectiveness
of a new or improved diagnostic or therapeutic intervention, more
effectively diagnose a disease, demonstrate the utility of biomarkers
or prognostic risk factors, and discover better ways to implement
health-improving interventions. The centerpiece of this area at NCATS
is the CTSA program.
The purpose of the CTSA program (http://www.ncats.nih.gov/research/
cts/ctsa/ctsa.html) is to support the entire spectrum of translational
research in order to accelerate the transition of laboratory
discoveries into patient studies and into clinical practice. Through
integrated homes that build on academic institutions' scientific
strengths, CTSAs provide expertise, resources, and workforce training,
which improve the quality, validity, generalizability, and efficiency
of clinical and translational research. For example, a team of
scientists with support from the University of California, Davis, CTSA
developed a test to determine the prevalence of a debilitating disease,
called Fragile X, in the general population. This information will help
researchers create screening and diagnostic strategies and allow
planning of clinical trial recruitment strategies for new Fragile X
therapies.
FOCUS ON RARE DISEASES
Targeting support to accelerate new treatments for rare diseases is
a major priority for NCATS. About 6,000 rare diseases affect an
estimated 25 million Americans; and, according to the Office of Orphan
Products Development, FDA, 450 orphan drugs have been approved, which
together treat only 250 of the 6,000 diseases. Discoveries about the
molecular basis of rare diseases based on the Human Genome Project
offer unprecedented scientific opportunities to change systematically
this landscape, by approaching rare diseases and their treatment as a
holistic systems-based problem, and NCATS is capitalizing upon these
opportunities. For example, the TRND program speeds the development of
new treatments for rare diseases of very low prevalence and otherwise
commercially neglected tropical diseases. It forms public-private
partnerships, which leverage the unique strengths and capabilities of
each party. Partnerships with disease foundations and/or biotech firms
helped bring promising therapies to the first-in-human testing stage
for chronic lymphocytic leukemia, sickle cell disease, hereditary
inclusion body myopathy, and Niemann-Pick Type C disease.
CONCLUSION
NCATS has sought to establish new technologies and paradigms that
can be implemented broadly to improve the efficiency of the
translational process for all and to broker collaborative development
of new interventions. We are grateful for the support of this
subcommittee for this new Center and look forward to sharing progress
with you each year.
______
Prepared Statement of Roger I. Glass, M.D., Ph.D., Director, Fogerty
International Center
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the Fogarty International Center
(FIC) of the National Institutes of Health (NIH). The fiscal year 2014
FIC budget of $72,864,000 includes an increase of $3,371,000 over the
comparable fiscal year 2012 appropriation of $69,493,000.
From leading the call for an AIDS-free generation to developing
vaccines and therapeutics for diseases that affect populations
worldwide, the United States is a global leader in health research and
scientific advances that improve the lives of Americans and people
across the globe. These discoveries are often made by U.S. and foreign
scientists working in close collaborations that enable the best and
brightest minds to tackle complex health challenges together. The
Fogarty International Center therefore supports innovative training and
research programs for U.S. and low- and middle-income country (LMIC)
scientists that strengthen the research capabilities and catalyze the
international scientific partnerships that lead to research discovery
and improved health. By investing in current and future leaders in
global health research and strengthening the long-term capacity of
research institutions to provide robust and sustainable platforms for
cutting-edge science, Fogarty advances the goals and extends the
leadership of the NIH and the U.S. Government in science and research,
while playing a vital role in building the capacity needed to
successfully tackle critical health challenges.
RECRUITING AND RETAINING DIVERSE SCIENTIFIC TALENT AND CREATIVITY
Fogarty programs have supported long-term research training for
more than 4,500 scientists worldwide, in collaboration with more than
230 U.S. and LMIC research institutions. These investments provide
unique training opportunities for early-career global health
researchers, and aid in the retention of diverse scientific talent in
the research enterprise. The vast contribution of FIC programs can be
seen in the over 5,000 PubMed publications citing FIC awards over the
last 5 years alone. Today's complex public health challenges benefit
when investigators from diverse fields work together to produce
transformative advances in science and technology. Fogarty's unique
``Framework Program for Global Health Innovation'' trains multi-
disciplinary teams of postdoctoral researchers to work together to
produce fresh insights into global health problems and develop
effective innovations for implementation in low-resource settings. For
example, with Fogarty support, a team of medical, engineering, and
architecture researchers from Boston, South Africa, and Peru is
designing and validating effective, affordable prototypes for air
disinfection. This work can not only help prevent airborne infections
such as tuberculosis and influenza from spreading in the low-resource
settings where they cause significant illness and death, but can also
potentially help higher income countries such as the United States
improve their programmatic approaches to airborne infection.
--Funded under the U.S. President's Emergency Plan for AIDS Relief
(PEPFAR) in collaboration with 18 NIH Institutes and Centers,
Fogarty and the Health Resources and Services Administration
(HRSA) jointly co-administer an innovative cross-U.S.
Government initiative funded primarily by the Office of the
Global AIDS Coordinator (OGAC) that is transforming medical
education and research training for medical students in 12
African countries. The 13 direct MEPI awardees and more than 40
partner institutions use a broad range of state-of-the-art
teaching and collaboration tools to train the next generation
of scientific leaders to solve their country's most pressing
health problems--from HIV/AIDS to maternal and child health,
and non-communicable conditions such as mental health and
cardiovascular disease. MEPI is increasing the quality,
quantity, and retention of medical faculty and physicians with
research skills, and building relationships with the public
sector partners that promote sustainable research capacity. For
example, Zimbabwe's Ministry of Education is now co-funding the
University of Zimbabwe's MEPI work.
TRANSLATIONAL SCIENCE
Fogarty programs support researchers who are generating the
critical scientific evidence that can be applied to specific
interventions, policies, and programs, and make a difference in
fighting disease and improving health.
--In recent years, we have seen that infectious diseases from animal
as well as human hosts can cause outbreaks that pose
significant health and economic threats to the U.S. and other
countries, Fogarty's ``Research and Policy in Infectious
Disease Dynamics (RAPIDD)'' program--co-funded by the
Department of Homeland Security (DHS)--brings together senior
infectious disease modelers and postdoctoral fellows to conduct
the research and develop infectious disease modeling approaches
that can help the U.S. and other policymakers plan for and
respond to potential infectious disease threats. ``RAPIDD''
models have contributed to a greater understanding of how Avian
Influenza and Hand, Foot, and Mouth disease can develop into
outbreaks from an initial case, and how these outbreaks can be
controlled effectively.
TODAY'S BASIC SCIENCE FOR TOMORROW'S BREAKTHROUGHS
Fogarty supports catalytic basic biomedical and behavioral research
that can lead to tomorrow's breakthroughs.
--Despite recognition of a looming antibiotic resistance crisis in
the U.S. and around the world, the number of new antibiotics
reaching the clinic continues to decline sharply, and most
recent discovery has been confined to minor modifications of
known antibiotics, with limited new therapeutic potential. The
Fogarty International Cooperative Biodiversity Groups (ICBG)
program, is working to change this. Fogarty-funded researchers
have developed an innovative and cost-effective approach to
antibiotic discovery, using an ``antibiotic mode of action
profile'' (BioMAP). BioMAP is a ground-breaking tool that can
be used to facilitate new natural products antibiotic discovery
and address the looming antibiotic crisis in the United States
and around the world.
--Brain disorders such as epilepsy and Alzheimer's pose significant
health problems around the globe. Fogarty's ``Brain Disorders''
program supports cutting-edge basic science research in LMICs
on the nervous system--research that could lead to new
diagnostics, prevention, and treatment strategies. In India,
for example, Fogarty grantees are exploring why Alzheimer's
affects Indian populations less than populations in developed
countries, with the goal of discovering useful evidence to
understand and mitigate Alzheimer's globally. In Uganda,
Fogarty-supported research is creating a base of knowledge on
dementia in those with long-term HIV infection, obtaining data
on prevalence, risk factors, and possible differentiation by
HIV sub-type that will be useful in understanding the course of
the disease and developing potential interventions worldwide.
FUTURE CHALLENGES
The need for sustainability poses a significant challenge for
investments in global health research and research training. Fogarty
investments continue to evolve with increasing research capabilities in
LMICs in order to build on successes and support the training of
individual scientists and strengthen research institutions. Fogarty's
deep regional expertise will continue to serve as a unique resource for
NIH and individual foreign scientists, institutions and countries that
are seeking new models and mechanisms that enable collaboration around
areas of mutual interest. In addition, Fogarty will increase support
for institutional networks and hubs for data collection and sharing.
When such sharing platforms are built around a core of trained
individuals and strengthened institutions, they can harness effectively
the different strengths of these institutions, and promote enhanced
efficiencies and more robust, collaborative science.
--Fogarty envisions that its U.S.-LMIC ``GEOHealth'' hubs will become
global leaders in the collection, management, synthesis, and
interpretation of data on environmental and occupational
health, serving the larger multi-national regions in which they
reside as well as supporting research of great relevance to
both these LMIC regions and the U.S.
--In sub-Saharan Africa, universities supported by ``MEPI'' are
emerging as regional training centers and upgrading the
technology to enable distance learning and resource-sharing
among institutions. This model is revolutionizing African
medical education and research training by enabling partner
institutions across Africa to pool their areas of expertise,
share teaching tools, and ensure that all students receive the
highest-quality instruction from the continent's best qualified
faculty and researchers.
In an increasingly interconnected world, the U.S. is often called
upon to play a leading role in addressing the world's most pressing
challenges. Fogarty programs harness the capabilities of the U.S. as a
leader of biomedical research, extend the frontiers of science,
accelerate discovery, improve the health of Americans and people across
the globe, and help the U.S. continue to compete and lead in science.
______
Prepared Statement of Donald A.B. Lindberg, M.D., Director, National
Library of Medicine
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for the National Library of Medicine
(NLM) of the National Institutes of Health (NIH). The fiscal year 2014
budget of $382,252,000 includes an increase of $17,365,000 over the
comparable fiscal year 2012 level of $364,887,000. Funds have been
included to allow the National Center for Biotechnology Information
(NCBI) to meet the challenges of collecting, organizing, analyzing, and
disseminating the deluge of data emanating from research in molecular
biology and genomics.
As the world's largest biomedical library and the producer of
internationally trusted electronic information services, NLM delivers
trillions of bytes of scientific data and health information to
millions of users every day. Many searches that begin in Google or a
mobile ``app'' actually retrieve information from an NLM Web site. NLM
is a key link in the chain that makes biomedical research results--DNA
sequences, clinical trials data, toxicology and environmental health
data, published articles, and consumer health information--readily
available to scientists, health professionals, and the public. A leader
in biomedical informatics and information technology, NLM also conducts
and supports leading-edge research and development in electronic health
records, clinical decision support, natural language processing,
information retrieval, imaging, computational biology,
telecommunications, and disaster response.
NLM's programs and services directly support NIH's key initiatives
in basic research, translational science, and research training, as
well as in Big Data. The Library organizes and provides access to the
published medical literature and massive amounts of scientific data
from high throughput sequencing; assembles data about small molecules
to support research and therapeutic discovery; provides the world's
largest clinical trials registry and results database; and is the
definitive source of published evidence for healthcare decisions. NLM's
PubMed Central (PMC) provides essential infrastructure for the NIH
Public Access Policy, which since 2008 has made published NIH-funded
research freely and permanently available to the public.
Research supported or conducted by NLM underpins today's electronic
health record systems. The Library has been the principal funder of
university-based informatics research training for 40 years, supporting
the development of today's leaders in informatics research and health
information technology. NLM's databases and its partnership with the
Nation's health sciences libraries deliver research results wherever
they can fuel discovery and support health decisionmaking.
RESEARCH INFORMATION RESOURCES
NLM's PubMed/MEDLINE database is the world's gateway to research
results published in the biomedical literature, linking to full-text
articles in PubMed Central, including those deposited under the NIH
Public Access Policy, and on publishers' Web sites, as well as
connecting to vast collections of scientific data. NLM is a primary
source for results of patient-centered outcomes research, providing
access to evidence on best practices to improve patient safety and
healthcare quality. The Library maintains an expanding collection of
full-text guidelines, evidence summaries, and systematic reviews from
authoritative agencies and organizations around the world.
NLM is also a hub for the international exchange and use of data
utilized in molecular biology, genomics, and clinical and translational
research. Many NCBI databases, including dbGaP, the Genetic Testing
Registry (GTR) and ClinVar, are fundamental to the identification of
important associations between genes and disease, and to the
translation of new knowledge into better diagnoses and treatments.
NLM's Lister Hill National Center for Biomedical Communications
operates ClinicalTrials.gov, the world's most comprehensive clinical
trials database. It contains registration data for more than 145,000
clinical studies with sites in 185 countries. ClinicalTrials.gov has
novel and flexible mechanisms that enable submission of summary results
data for clinical trials subject to the Food and Drug Administration
(FDA) Amendments Act of 2007. Summary results are available for nearly
9,000 completed trials of FDA-approved drugs, biological products, and
devices--providing a new and growing source of evidence on efficacy and
comparative effectiveness. NLM will leverage experience with these
resources and its research in related fields to contribute to NIH
efforts to improve access to other types of NIH-funded Big Data.
HEALTH DATA STANDARDS AND ELECTRONIC HEALTH RECORDS
Electronic health records (EHRs) with advanced decision-support
capabilities and connections to relevant health information are
essential to improving healthcare and helping Americans manage their
own health. For 40 years, NLM has supported seminal research on
electronic patient records, clinical decision support, and health
information exchange, including concepts and methods now reflected in
EHR products and personal health record tools. As the Department of
Health and Human Services (HHS) coordinating body for clinical
terminology standards, NLM works closely with the Office of the
National Coordinator for Health Information Technology and the Centers
for Medicare and Medicaid Services to facilitate adoption and
``meaningful use'' of EHRs. NLM supports, develops, and distributes key
terminology standards now required for U.S. health information
exchange. To help EHR developers implement standard terminologies, NLM
produces related software tools, frequently used subsets, and mappings
to administrative code sets, and provides the authoritative versions of
terminology value sets for required clinical quality measures. NLM's
MedlinePlus Connect also supports meaningful use by providing a way for
EHR products to link patients to high quality health information
relevant to a specific health conditions, medications, and tests,
directly from their EHRs.
INFORMATION SERVICES FOR THE PUBLIC
This EHR connection builds upon NLM's extensive information
services for patients, families and the public. The Library's
MedlinePlus Web site provides integrated access to high quality
consumer health information produced by all NIH components and
Department of Health and Human Services (DHHS) agencies, other Federal
departments, and authoritative private organizations. It serves as a
gateway to specialized NLM information sources for consumers, such as
the Genetic Home Reference and the Household Products Database.
Available in English and Spanish, with selected information in 40 other
languages, MedlinePlus averages well over 750,000 visits per day.
Mobile MedlinePlus, also in both English and Spanish, reaches the large
and rapidly growing mobile Internet audience.
The ``NIH MedlinePlus'' magazine, in English and Spanish, is an
outreach effort made possible with support from many parts of NIH and
the Friends of the NLM. Distributed free to the public via physician
offices, community health centers, libraries and other locations, the
magazine reaches a readership of up to 5 million nationwide. Each issue
focuses on the latest research results, clinical trials and guidelines
from the 27 NIH Institutes and Centers.
To be of greatest use to the widest audience, NLM's information
services must be known and readily accessible. The Library's outreach
program, with a special emphasis on reaching underserved populations,
relies heavily on the more than 6,000-member National Network of
Libraries of Medicine (NN/LM). The NN/LM is a network of academic
health sciences libraries, hospital libraries, public libraries and
community-based organizations working to bring the message about NLM's
free, high-quality health information resources to communities across
the Nation.
INFORMATION FOR DISASTER AND EMERGENCY RESPONSE
NLM builds on proven emergency backup and response mechanisms
within the NN/LM to promote effective use of libraries and information
specialists in disaster preparedness and response. NLM conducts
research on new methods for sharing and ensuring continued access to
health information in emergencies, including as its contribution to the
Bethesda Hospital Emergency Preparedness Partnership, a model of
private-public hospital collaboration for coordinated disaster
planning. NLM works with the Pan American Health Organization (PAHO)
and the Latin American Network for Disaster and Health Information to
promote capacity-building in disaster information management. In
addition, NLM responds to specific disasters worldwide with specialized
information resources appropriate to the need. Mobile apps and tools
developed for first responders have been downloaded nearly 500,000
times worldwide.
In summary, NLM's information services and research programs serve
the Nation and the world by supporting scientific discovery, clinical
research, education, healthcare delivery, public health response, and
the empowerment of people to improve personal health. The Library is
committed to the innovative use of computing and communications to
enhance public access to the results of biomedical research.
______
Prepared Statement of Jack E. Whitescarver, Ph.D., Director, Office of
AIDS Research
Mr. Chairman and members of the committee: I am pleased to present
the President's budget request for fiscal year 2014 for the trans-NIH
AIDS research program, which is $3,121,716,000. This amount is
$46,921,000 above the comparable fiscal year 2012 level of
$3,074,795,000. It includes the total NIH funding for research on HIV/
AIDS and the wide spectrum of AIDS-associated malignancies,
opportunistic infections, co-infections, and clinical complications;
intramural and extramural research; research management support;
research centers; and training.
NATIONAL INSTITUTES OF HEALTH AIDS RESEARCH ACCOMPLISHMENTS
In the three decades since AIDS was first reported, NIH has been
the global leader in research to understand, prevent, diagnose, and
treat HIV and its many related conditions. From the development of the
first blood test for HIV infection and the discovery and clinical
testing of the first effective therapies, through today's research to
determine whether a vaccine, microbicide, or eventual cure for AIDS
will one day be possible, NIH research has transformed HIV from a
mysterious and uniformly fatal infection into one that can be
accurately diagnosed and effectively managed with appropriate
treatment. A recent study estimated that 14.4 million life years have
been gained since 1995 by the use of AIDS therapies developed as a
result of NIH-funded research. Recent discoveries include:
--Development of new treatments for many HIV-associated co-
infections, comorbidities, malignancies, and clinical
manifestations;
--Development of new strategies for the prevention of mother-to-child
transmission (MTCT), which have resulted in dramatic decreases
in perinatal HIV in the U.S., where now fewer than 100 babies a
year are born with HIV infection;
--Demonstration of the first proof of concept that a vaccine can
prevent HIV infection and identification of potential immune
markers for protection;
--Discovery of more than 20 potent human antibodies that can stop up
to 95 percent of known global HIV strains from infecting human
cells in the laboratory;
--Demonstration of the first proof of concept that a microbicide gel
can prevent HIV transmission;
--Demonstration that the use of antiretroviral therapy by infected
individuals can reduce HIV transmission to an uninfected
partner dramatically;
--Demonstration of the feasibility of pre-exposure prophylaxis
(PrEP), the use of antiretroviral treatment regimens by
uninfected individuals to reduce their risk of HIV acquisition;
--Discovery that genetic variants may play a role in enabling some
individuals, known as ``elite controllers,'' to control HIV
infection without therapy;
--Critical basic science discoveries that continue to provide the
foundation for novel research; and
--Advances in basic and treatment research aimed at eliminating viral
reservoirs in the body that for the first time are leading
scientists to design and conduct research aimed at a cure for
HIV/AIDS.
THE AIDS PANDEMIC
In spite of these advances, the HIV/AIDS pandemic remains a global
scourge. UNAIDS reports that in 2011, more than 34 million people were
estimated to be living with HIV/AIDS; 2.5 million were newly infected;
and 1.7 million people died of AIDS-related illnesses. The majority of
cases worldwide are the result of heterosexual transmission, and women
represent more than 50 percent of HIV infections worldwide. More than
25 million men, women, and children worldwide have already died. Around
330,000 children were newly infected with HIV in 2011, a reduction of
24 percent in just 2 years--from 2009-2011--a result of the
distribution of HIV treatment to prevent mother-to-child transmission
developed by NIH research.
In the United States, the Centers for Disease Control and
Prevention estimates that approximately 1.2 million people are HIV-
infected; approximately 50,300 new infections occur each year; and one
in four people living with HIV infection in the U.S. is female. HIV/
AIDS continues to be an unrelenting public health crisis,
disproportionately affecting racial and ethnic populations, women of
color, young adults, and men who have sex with men. The number of
individuals aged 50 years and older living with HIV/AIDS is increasing,
due in part to antiretroviral therapy, which has made it possible for
many HIV-infected persons to live longer, but also due to new
infections in individuals over the age of 50.
COORDINATED TRANS-NIH AIDS RESEARCH PROGRAM
The NIH AIDS research program is coordinated and managed by the
Office of AIDS Research (OAR), which functions as an ``institute
without walls'' with responsibility for AIDS-related research supported
by nearly every NIH Institute and Center (IC). OAR coordinates the
scientific, budgetary, and policy elements of the trans-NIH AIDS
research.
Through its unique trans-NIH planning, budget, and portfolio review
processes, OAR identifies the highest priority areas of scientific
opportunity and ensures that precious research dollars are invested
effectively.
In collaboration with both Government and non-Government experts,
OAR develops the trans-NIH AIDS strategic Plan. The priorities of the
Plan guide the development of the trans-NIH AIDS research budget. OAR
develops each IC's AIDS research allocation based on the Plan,
scientific opportunities, and the IC's capacity to absorb and expend
resources for the most meritorious science--not on a formula. This
process reduces redundancy, promotes harmonization, and ensures cross-
Institute collaboration. OAR has the authority to shift resources
across ICs and areas of science to meet the needs of the changing
epidemic and scientific opportunities.
NEW SCIENTIFIC ADVANCES AND OPPORTUNITIES
The advances made by NIH investigators have opened doors for new
and exciting research opportunities to answer key scientific questions
that remain in the search for strategies to prevent and treat HIV
infection both in the U.S. and around the world. These advances
represent the building blocks for the development of this trans-NIH
AIDS research budget request. These include:
--Basic research that will underpin further development of critically
needed ``vaccines and microbicides''.
--Innovative multi-disciplinary research and international
collaborations to develop novel approaches and strategies to
eliminate viral reservoirs that could lead toward ``a cure for
HIV''.
--Critical studies in the area of ``therapeutics as a method to
prevent infection'', including treatment to prevent HIV
transmission; Pre-Exposure Prophylaxis; a potential prevention
strategy, known as ``test and treat,'' to determine whether a
community-wide testing program with treatment can decrease the
overall rate of new HIV infections; and improved strategies to
prevent mother-to-child transmission. A key priority is to
evaluate prevention interventions that can be used in
combination in different populations, including adolescents and
older individuals.
--Research to develop better, less toxic treatments and to
investigate how genetic determinants, sex, gender, race, age,
nutritional status, treatment during pregnancy, and other
factors interact to affect treatment success or failure and/or
disease progression.
--Studies to address the increased incidence of malignancies;
cardiovascular, neurological and metabolic complications; and
premature aging associated with long-term HIV disease and
antiretroviral treatment (ART).
--Research on the feasibility, effectiveness, and sustainability
required to scale-up interventions from a structured behavioral
or clinical study to a broader ``real world'' setting.
FUNDING PRIORITIES
OAR has utilized its authorities to shift AIDS research resources
across ICs to meet the new and exciting scientific opportunities in
AIDS research. These shifts reflect the scientific priorities
identified in the annual trans-NIH strategic planning and budget
process and address the evolving clinical profile of the epidemic,
changing demographics, and most recent scientific advances. In this
budget request, OAR has provided increases to high-priority basic
research (etiology and pathogenesis) that provides the underlying
foundation for all HIV research. An important area will focus on
research related to the potential for a cure or lifelong remission of
HIV infection, including studies on viral persistence, latency, and
reactivation. Increases are also provided for the development of
vaccines and microbicides to prevent HIV infection. In order to provide
those increases, OAR has reduced and redirected funds from natural
history and epidemiology, therapeutic clinical trials, and training and
infrastructure support.
SUMMARY
The NIH investment in AIDS research has produced groundbreaking
scientific advances. AIDS research also is helping to unravel the
mysteries surrounding many other cardiovascular, malignant, neurologic,
autoimmune, metabolic, and infectious diseases, as well as the complex
issues of aging and dementia. Despite these advances, however, AIDS is
not over, and serious challenges lie ahead. The HIV/AIDS pandemic will
remain the most serious public health crisis of our time until better,
more effective, and affordable prevention and treatment regimens are
developed and universally available. NIH will continue to search for
solutions to prevent, treat, and eventually cure AIDS.
Senator Harkin. Thank you, again, Dr. Collins, for your
statement, and for bringing us up-to-date.
We'll begin a round of 5-minute questions.
Who is running the time here? There we go.
So we'll begin a round of 5-minute questions. I'm sure
we'll have more than one round.
FAVORING SAFER VERSUS INNOVATIVE RESEARCH PROJECT GRANTS
So, Dr. Collins, as I said in my opening statement, I think
you repeated it, that the reviewed NIH grants will drop to
about 16 percent this fiscal year. I'm concerned that when
money gets that tight, there's a tendency to shy away from
awarding ideas that are thinking outside the box, and we've
talked about that many times here with you over the last many
years.
I'm concerned that, consciously or unconsciously, your peer
reviewers might tend to favor safer incremental advances and to
avoid ideas that are bolder but may carry more risk. Any
validity to that?
Dr. Collins. Mr. Chairman, that's certainly an area of
considerable concern for all of us, because imagine yourself on
a study section where you have a big pile of exciting science
in front of you and you know you're going to only be able to
fund a very small number of those. You have in front of you a
really powerful strong proposal that builds on previous work
from an established investigator that you know is going to be
successful, and then you got something over here that's a bit
risky from an investigator who doesn't have the same track
record.
If it works, it could be groundbreaking, but you're not
sure it's going to work. And in that setting where you would
love to fund both, but you may not be able to, there can be a
tendency then to go with what you know is going to produce
results. But that could be just the wrong thing to do.
We in NIH have a number of programs that aim to try to
encourage innovation in this climate by setting up programs
like the Pioneer Awards, the Transformative RO1s, the New
Innovator awards. You can't apply to those programs unless you
have an out-of-the-box idea.
So, there's this common fund effort to do that, and many of
the institutes have initiated efforts of that sort as well.
But there's no question about it. There's no magic here in
terms of loss of innovation potential. Just the fact that we're
only funding 15, 16 percent or less of the applications that
come in, there's a lot of innovation at the 18th percentile and
the 22nd percentile. Most of us have a very hard time telling
the difference between a grant that scores at the 11th
percentile and the 17th. Yet, one is going to get funded and
one may not.
So, the real anxiety we all feel is how much talent is
being wasted and how many ideas are not getting followed up on
that could be.
EFFECTS OF SEQUESTRATION ON RESEARCH PROJECT GRANTS
Senator Harkin. So sequestration has an effect on that
also?
Dr. Collins. Absolutely, because sequestration drops the--
as we've all just mentioned, 700 grants that we hoped we would
fund this year are not going to be. I'm sure in those 700 there
were some great, innovative, out-of-the-box ideas.
NCI'S PROVOCATIVE QUESTION INITIATIVE
Senator Harkin. Okay. I'm going to go to Dr. Varmus,
talking about thinking out-of-the-box and everything. Tell us
more about your Provocative Questions program, and what's the
purpose, and how is it proceeding?
Dr. Varmus. We did two things to try to ensure that we do
the best we can, imperfect though that is, to address the
concerns you and many others have raised about risk-taking
under these adverse fiscal circumstances.
The first thing we do is to look at a large number of our
grant applications, and award grants even when the score is a
little less than you might think is required for success by
saying this is really innovative and addresses a very important
issue.
Number two, we set up some special programs, one of which
is called Provocative Questions. These questions come from
groups that we assemble around the country, interdisciplinary
groups, people who haven't been in cancer research before, to
raise some difficult questions that we think technology now may
be prepared to address. We have these questions debated on our
Web site. We then invite applications for answering about 24
each year, and we're funding--last year, over 50; this year we
hope more than that--to try to address the 24 questions that
we've been selecting as particularly important and difficult
questions.
Too early to say how well we're going to do with this, but
it's a way to try to guarantee some answer to the question
you're appropriately raising.
BRAIN INITIATIVE: WHAT IS IT?
Senator Harkin. I'll have a follow-up question on that
later, but I wanted to ask Dr. Landis, in the short time I have
left, about the new BRAIN Initiative.
The President talked about mapping the brain, what does it
mean? Someone compared it to, again, the Human Genome Project.
But even at the beginning, some of us were there at the
beginning, we knew what the end result was going to be, and we
knew when it was going to end. We didn't know exactly when, but
we knew what the end result was.
What do we know about what is the end result? Is there
something that we're looking to reach at a certain point in
time?
Dr. Landis. So, what we would really like to be able to do
with the BRAIN Initiative is to understand how information is
processed in circuits. As Dr. Collins told you, we're beginning
to have better maps of connections between nerve cells in
different regions of the brain. And, we can lay them out in
circuits that control particular movements, vision, or hearing.
But what we don't understand is how information is
processed through those pathways. And in order to understand a
number of psychiatric diseases and even neurodegenerative
diseases, we have to understand how circuits work. We simply do
not have the tools to do that now. So, that would be one of the
major goals for the first 5 years of the BRAIN Initiative, to
get better tools and technologies that will be able to help us
track activity in circuits, and understand how information
changes as it goes from one nerve cell in a circuit to another.
Much more, as I've already said to Dr. Collins, much more
complicated than just lining up the As and Cs and Ts and Gs,
but could have as much, or even greater, impact. And he did
agree with me on that.
Senator Harkin. Yes, but 3 billion base pairs, we thought
that was a lot. Now we're talking about a trillion or something
like that. I don't know. We'll get back to that.
Senator Moran.
Senator Moran. Mr. Chairman, thank you very much.
Dr. Collins, thank you very much for your compelling
testimony.
Dr. Varmus, thank you for coming to Kansas City and
visiting a couple of facilities, a research facility and a
hospital. But thank you especially for riding your bike to
raise money for cancer research.
Dr. Varmus. Along with the barbeque.
Senator Moran. Along with the barbeque. That's right. That
was the real inducement. Thank you very much for highlighting
Kansas City barbeque.
BRAIN INITIATIVE: 10-YEAR BUDGET
Dr. Collins, and this may be this is for Dr. Landis,
because it's a follow-up to what the chairman was asking about.
On the BRAIN Initiative, the budget documents are not very
specific in regard to what we should expect as far as budget
requests in the next 10 years.
I was interested in what the goals are in the short term of
this project. You outlined already what, at least in the first
5 years, is the significant goal. But what would we as a
committee, what would we as members of the Senate, expect the
request to be in regard to the budget into the future?
Dr. Collins. So, a very appropriate question. This is sort
of like the genome project in 1988 where it was clear there was
an opportunity, and it wouldn't happen without a coordinated
effort, particularly the focus on technology. But nobody was
quite sure at that point what the trajectory could look like as
far as accomplishing that goal.
We're in the process right now of trying to define that,
Senator, in the long term, over the next 10 or 15 years. What
could be accomplished? What would the steps be? What kind of
technologies do we need? And what would the cost be?
So, we brought together a really remarkable group of
visionary neuroscientists in a group--co-chaired by Cori
Bargmann from Rockefeller and Bill Newsome from Stanford along
with 13 other remarkable folks--and we've asked them, in the
course of the next few months, and they're hard at work at
this, to lay out some initial milestones of what this project
needs to accomplish. And by the summer of 2014, to have a much
more detailed roadmap of where the BRAIN Initiative needs to go
and how quickly it can get there.
So, frankly, I don't have a clear answer to your question
at the moment, in terms of what the budget trajectory of this
might be over the next 10 or 15 years. We have to be sure we
have the science plan laid out.
Senator Moran. And there's no justifiable reason that we
should expect that plan at this point? That's just not
accomplishable, at this point? Before we start down this path,
we're not going to know what to expect?
Dr. Collins. I think at this point, it would be premature
to try to attach budget numbers to a scientific plan that
hasn't quite formed in a coalesced way and been embraced and
endorsed by all of the scientific experts that we want to
participate and to take part in this.
So, it has always been our view that if you're going to try
to start something really bold, the first step is to map out
the science, and then you figure out, okay, what does that mean
in terms of the timetables and the costs? Of course, you have
to set priorities within the realistic envelope of what costs
might be available to you.
We recognize this may be a tough time to be starting a very
ambitious project, but we just don't think it would be right to
wait, given the opportunity.
STATUS OF NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
Senator Moran. Dr. Collins, this might be for you, as I
don't think the National Center for Advancing Translational
Sciences (NCATS) director is here.
Dr. Collins. He is not.
Senator Moran. Let me ask about the status of NCATS. I was
supportive of its establishment. I think that is now about a
year and a half ago. And I'd be interested in having you bring
me up-to-date on its developments.
One of the environments in which NCATS now works is that
with the economic conditions we face, private drug companies
can no longer make a financially sound business case to invest
in new drug development projects. There's this gap, what has
been described as a valley of death between scientific
discovery on the one side and patient benefit and commercial
success on the other.
The goal of NCATS has been to fill that valley. What kind
of success is NCATS having in doing that?
Dr. Collins. Well, thank you for the question.
Let me say right upfront how wonderful it's been for Chris
Austin, the Director of NCATS, to work with folks in Kansas at
the university and with the Leukemia and Lymphoma Society on a
few groundbreaking projects. Particularly one on chronic
lymphocytic leukemia (CLL), which is actually a good example of
one of the things I want to mention that NCATS is catalyzed,
and that is this whole idea of repurposing drugs that were
developed for something but turned out to have a use for
something else.
The project they're working on with Kansas is a drug
developed for rheumatoid arthritis, Auranofin, which turns out
to have activity against leukemia, and more recently to the
delight of all of us, also against a very resistant kind of
cancer called mantle cell lymphoma.
The CLL protocol is already well along in a clinical trial.
This is an amazing quick turnaround, because if you had to
start from scratch, it would take years and tens of millions of
dollars to get to a clinical trial. But, if you can identify a
compound and try it for a new purpose, you already have all
that background data and you shave off years and many, many
tens of millions of dollars in cost.
So, NCATS is in fact catalyzing that kind of repurposing
both for drugs that have already been approved but also in
working with companies, eight of them, they have agreed to make
58 compounds available for new uses that actually turned out
not to be effective for the original use but the drugs are
known to be safe.
This is crowdsourcing, if you will, the opportunity to find
a new use for a really heavily invested compound that may turn
out to have failed for disease A but might be just the thing
for disease B.
NCATS is also working with the Food and Drug Administration
(FDA) and with Defense Advanced Research Projects Agency
(DARPA) on developing a new and very high-tech way of
identifying whether or not a drug is going to be safe before
you ever give it to that first human patient, using a biochip
depending upon the stem cell, iPS cell technology.
NCATS also serves now as the home for the largest
investment in clinical and translational science, namely our
Clinical and Translational Science Award (CTSA), of which they
are 60 across the country in many of your States, and basically
then bringing that network together in a way that makes the
whole really much greater than the sum of the parts, sort of
CTSA 2.0, as we are starting to call it.
So, I think even though NCATS has only been around for, you
know, a year and maybe 5 months, the evidence is very clear
that this is an opportunity that we have grabbed on to. The
private sector is enthusiastic about the way in which this
serves as a complementary set of contributions to what they are
doing. Academics are fired up about it. I think this has turned
out to be a really good thing for NIH, too.
Senator Moran. Very good.
I assume you're the one who coined the phrase ``valley of
death'' and now ``crowdsourcing.'' I will use it in my comments
next.
Dr. Collins. I don't think I can take credit, but you are
welcome to use the terms.
Senator Harkin. Senator Mikulski, Senator Shelby, Senator
Cochran.
Senator Mikulski.
Chairwoman Mikulski. Thank you very much, Mr. Chairman.
And, Dr. Collins, I want to welcome you and your entire
team, and also other heads of institutes who are not at the
blue table but are certainly always at the head of the line at
the head table.
I just wanted to just tell you in the warmest way, and to
my colleagues, what a sense of joy and pride that I have
representing NIH. The fact that it is located in my home State
of Maryland, Senator Cardin and I both know that every day, to
have such a premier institution is one of the reasons we want
to be in the Senate, really to be an advocate for the kinds of
resources, policy, and framework, so you get to be you and you
get to be what the American people want you to do, which is to
find cures to disease, to find containments of disease, to look
for those things to even prevent them from happening or prevent
them from escalating.
So it's not only a source of pride, but I can tell you, as
the chair of this full committee, I'm going to work with
Senator Harkin and Senator Moran across party lines, to make
sure they get the kind of allocation they need to do their job.
Much has been said here about sequester. I'm not going to
go into it in detail, but I'm concerned about the negative
impact that it has, first of all on the people who work at NIH
and those who participate in the extramural programs, like the
University of Maryland, like Hopkins, like the great land-grant
universities that, again, are out there working every day.
That's the genius of what we do.
It's not Government-owned and operated. It's also out there
extramurally and also functioning around the world, because who
you are, you talk to the others around the world.
And, therefore, we need to look at the impact of sequester
on jobs, on the economy, and not only on our reducing public
debt today, but the impact on growth.
I am just struck by what you've done. Deaths from heart
attacks and strokes have fallen more than 60 percent--60
percent. A wonderful colleague like Mark Kirk could make it up
the steps of the Capitol when he was sworn in for his comeback
into the United States Senate because of his grit, his verve,
and the medical science behind him.
This is not only for a member of the United States Senate;
it's for all Americans.
HIV/AIDS--we remember, Dr. Fauci, when the crisis came. We
were here when a little boy named Ryan White testified. He was
kept isolated in his own class in school because nobody would
talk to him. HIV/AIDS, thanks to your work and the brilliant
scientists, are no longer a death sentence.
And for the children of the world in our own country,
children with the most common childhood leukemia have a 90
percent chance of surviving.
What a phenomenal story.
Dr. Varmus, you were the Director of NIH. You go to Sloan-
Kettering. You have one of those cushy, full professorships
that most people dream about. You come back to head up an
institute. You announce that cancer rates are down 12 to 15
percent across the board.
This is just stunning. And yesterday we saw a brilliant
actress, an esteemed actress take the bold step, announcing the
bold step where she had a prophylactic mastectomy in order to
ensure her own survival rate. But she knew her genetic
situation. She could have decisions, informed consent. This is
who we are, and this is what we're fighting for.
I didn't mean to give a speech, but I'm so excited about
you.
And I want to say to my colleagues, this is why we have to
not only--this sequester I think has a very deleterious,
eroding, and corrosive effect. So I want to do all I can to
cancel sequester this year, and also cancel sequester for the
next 9 years, for which you would then fall behind to the tune
of $19 billion.
We hope that the other side--we've got support here on the
other side of the aisle. I worry about the other side of the
dome.
Mr. Ryan, in his budget, is sending it to us to work with
at $966 billion. That's bad enough, but he took all of it out
of domestic discretionary spending.
I'm not going to turn this into politics. We want to be
above politics. But we're going to have to deal with politics.
I want my subcommittee chairman and the vice chairman of
this subcommittee to know, I want to work with them, because
what I see my job as doing is to do all we can to help you be
you and help you do the mission that the United States of
America and its people gave you.
So I'm going to work my earrings off to make that happen.
And with that, I just wish we could even get more done.
I'm not going to ask questions. I've taken a lot of the
time here. I will be interested in the further discussion that
we're having.
Senator Harkin. Madam Chairman, thank you very, very much
for your leadership of this full committee, and not only your
leadership of the full committee, but your great leadership on
this particular subcommittee. For all of the input and
leadership you've given us through all these years, we thank
you very much.
Now, we'll turn to Senator Shelby.
Senator Shelby. Thank you.
First of all, I want to associate myself with the remarks
of Senator Mikulski. She said it so well.
I believe that the top investment we can make in America to
save lives, to improve lives, for the American people is to
invest in the NIH. I believe this.
I'd like to see us double NIH's funding. I know that's hard
to do, but to at least get on the upward funding trend, not the
downward trend, of biomedical research in this country is a
critical first step.
And I'm saying that because I see the results of NIH
research, as Senator Mikulski has pointed out, Senator Harkin
has, and others, Senator Moran.
RESEARCH AND ITS IMPACT ON THE STANDARD OF CARE
Having said that, Dr. Collins, I want to get a little
parochial, if I can.
Researchers at the University of Alabama in Birmingham, as
you well know, conducted an important study on very premature
babies, a study called ``SUPPORT'' from 2004 to 2009 that was
funded by the National Institutes of Health. Researchers at
more than 20 sites were trying to determine, as I understand
it, the proper oxygen levels for these vulnerable premature
babies by comparing two ranges of oxygen saturation within the
standard of care at that time.
It's my understanding that the SUPPORT study has had an
important effect on clinical care. Dr. Collins, how important
is research like this that study and ultimately improve the
standard of care?
Dr. Collins. Senator Shelby, thank you for the question.
Very important, indeed. Standard of care reflects what we
know at the time, and oftentimes, we don't know enough, and so
it may be a rather broad range of options and physicians and
other caregivers who are trying to do the best job of taking
care of patients. And patients who are seeking the best care
may not be well-served by all, the entire range, of
opportunities that are called standard of care.
That was certainly the case for the study of the optimum
oxygen levels to give to premature babies.
Senator Shelby. But you learn by investigating and by
studying. That's the bottom-line.
Dr. Collins. You're exactly right.
So, for us at NIH, we invest heavily in these kinds of
studies. Let me give you another couple of examples.
Individuals who are going through hemodialysis, and there
are a lot, sad to say, many of them because of diabetes. There
has never really been a clear understanding of what the right
schedule is for hemodialysis, how many times a week, how many
hours. That's a huge impact on somebody's quality of life, in
terms of how much time they're spending there. But also,
quality of life is dependent on how effective the dialysis is.
So, a study called the Frequent Hemodialysis Network (FHN):
Daily Trial, that we have been funding, aimed to try to get an
answer to that. All in the standard of care, everybody in that
study, is getting the kind of treatment that you would consider
standard, but we're trying to find the sweet spot, to do a
refinement of that.
I could cite you two or three others. This is very
important and yet we depend upon patient----
Senator Shelby. It goes to the basis of your research, does
it not?
Dr. Collins. Yes, it does. That's what our goal is, is to
try to be sure that people get the best possible information in
order to guide their medical care.
UNIVERSITY OF ALABAMA AT BIRMINGHAM INFANCY CLINICAL STUDY
Senator Shelby. As you well know, the University of Alabama
at Birmingham (UAB) received a letter from the Office of Human
Research Protection (OHRP) about the SUPPORT clinical trial
that we're carrying out under the auspices of NIH. And the OHRP
determined that UAB should have informed parents of an
increased risk of death of their infant by participating in the
study. But it was my understanding that the risks were unknown
at the time of the study's commencement in 2004, and there was
no specific scientific data that existed at the start of the
study that showed an increased risk.
Were babies in that study at any greater risk than babies
not in the study? Do you know?
Dr. Collins. No, Senator. I don't believe they were.
Senator Shelby. Okay.
INSTITUTIONAL DEVELOPMENT AWARDS PROGRAM ELIGIBILITY CRITERIA
We've talked about the sequester, I'll move on, on that.
I'm committed to working with Senator Mikulski to see if we can
plus-up NIH, though.
Institutional Development Awards (IDeA), we discussed this
topic a little bit before. I think it's important to recognize
that the next scientific discovery may come from anywhere. You
don't really know where. And I believe that institutions that
do not historically have high NIH grant rates can still
substantially contribute to biomedical research. And I believe
we need to give these institutions an opportunity.
As we discussed before, Dr. Collins, the eligibility
criteria for the IDeA program is outdated. Both the fiscal
years 2012 and 2013 Senate Labor-HHS bills included report
language regarding this issue.
However, it's my understanding that no significant
information on the subject has ever been provided to the
subcommittee.
Dr. Collins, could you work with us to develop a better
criteria, eligibility criteria, for some of these institutions
that really could contribute, if given a chance?
Dr. Collins. So, Senator, I know time is short, but I'll
answer quickly. I do agree that it's a wonderful opportunity
for capacity-building in this competitive program that is known
by the name of IDeA.
The Institute of Medicine has been undertaking a study of
whether the criteria for IDeA and Experimental Program to
Stimulate Competitive Research (EPSCOR) are in fact in need of
revision, and we expect that report to be released fairly soon.
It would be a good time then to have a conversation with you
and others about this issue.
BREAKTHROUGHS IN CYSTIC FIBROSIS
Senator Shelby. Let's talk about, if we could, the
breakthroughs in the research that has been done in cystic
fibrosis over the years. We've talked about this before, and
there's been some breakthroughs there.
Would you highlight some of them, and how we're doing in
that area?
Dr. Collins. It's an area of enormous excitement. My own
research lab back in 1989 played a role in collaborating with
another group in Toronto in discovering the gene for cystic
fibrosis. And now, just in the last couple of years, the really
exciting fruits of that in terms of drug therapy have emerged
with one drug called Kalydeco now approved in record time by
the FDA, which shows dramatic responses from individuals who
have a particular misspelling of that cystic fibrosis gene.
Unfortunately, only about 4 or 5 percent of cystic fibrosis
patients are in that category. But there's great excitement
because of phase II and phase III trials now being conducted by
Vertex on two new compounds, which should be actually quite
useful for 90 percent or more of people with cystic fibrosis.
This all builds upon NIH research that's been done over the
decades. It's a wonderful collaboration with the Cystic
Fibrosis Foundation in interaction with the company called
Vertex. The National Heart, Lung, and Blood Institute, which
Dr. Gibbons directs, has funded a lot of this effort through
the years. It is a great success story, and one that we hope to
replicate for lots of other diseases.
Senator Shelby. Thank you for sharing it with us.
Thank you, Mr. Chairman.
Senator Harkin. Senator Cochran.
Senator Cochran. Mr. Chairman, I'm pleased to join you in
welcoming our distinguished panel of witnesses today.
Dr. Collins, we appreciate your being here again and also
coming out into the countryside where we live and work.
Dr. Collins. I enjoy that very much, Senator.
Senator Cochran. We appreciated the honor of your visit to
Mississippi.
And it might interest you to know that just recently, there
was an announcement from the Blair Batson Hospital for Children
in Jackson, Mississippi, where you were, by a Dr. Hannah Gay,
who reported a functional cure of a child who was born HIV
positive. And this is news that's getting around the world now
and is attracting attention again to the distinction that
Mississippi has for people like Dr. Arthur Guyton, who wrote
many of your textbooks, and others who have pioneered in
research in different areas.
So we look forward to supporting the work that you do, and
we hope we'll be able to provide some seed money or incentive
grants, funding to ensure that we continue to embark upon
daring and innovative approaches to dealing with our health
problems in America.
Thank you.
Senator Harkin. Senator Boozman.
Senator Boozman. Thank you all, and thank you for being
here. I really do want to compliment you all as a group. Your
efforts, your work, your advocacy really has changed the world,
and we appreciate your efforts very, very much.
There's a lot of things that the Government possibly, we
could argue, doesn't need to be doing. I think what you all
represent is something the State of Arkansas, our communities,
can't do individually, and so we do appreciate the work that
you do.
PUBLIC ACCESS TO NIH RESEARCH
One thing I'd like to ask about, we have to make some
significant decisions here. The agencies have to make some
significant decisions. As we have research that is publicly
funded, generally, we allow that research to be made available;
is that correct?
Dr. Collins. Yes, we strongly support the need for that. If
the public has paid for the research, the public should have
access to it. I think NIH, it's fair to say, has taken the lead
in trying to make sure that that kind of access to information
happens in a timely fashion.
The recent suggestion, by the Obama administration, is that
this kind of policy should be applied broadly across all of the
agencies, and I think many are looking at NIH's model as
something to replicate in other parts of the Government as
well.
DUAL-USE RESEARCH SAFEGUARDS
Senator Boozman. And again, I appreciate that and agree
wholeheartedly. And I'm glad that that is the policy.
Can you envision a reason not to do that in some cases?
Dr. Collins. Perhaps you're talking about circumstances
where the data that's being generated might in fact create some
risk to the public if it fell into the wrong hands.
I'm going to ask Dr. Fauci to comment on this, because this
often falls in the category of areas that might be amenable to
bioterrorist misuse, and we've certainly been engaged in those
conversations. And Dr. Fauci has had the lead in many of them.
Tony?
Dr. Fauci. Yes, thank you for that question.
It is a delicate balance, particularly when you do what is
called dual-use research of concern, where the public health
imperative for understanding whatever process you're looking at
is quite important. Yet you're concerned with two things.
One is the deliberate misuse of things that have to do, for
example, with potentially pathogenic microbes that could be
used in a bioterror situation or the inappropriate and careless
use of that information by people who are not qualified. It
transcends all areas of research, but it's particularly acute
when you're dealing with the study and perhaps even creation of
a microbe that might, in fact, be an issue.
Having said that, we tend, unless there's a really very
good reason, to be as open and transparent as possible, because
the default rule--and we're careful about that and not
careless--is that not allowing knowledge to be generally spread
throughout the scientific community has more deleterious
effects than the risk of having something being used in a
deleterious way accidentally or deliberately by others.
So, it goes along with the concept that Dr. Collins
mentioned, that we have been the leaders and we continue to
stress the open nature of scientific information.
CLINICAL TRIALS AND VOLUNTEER CONFIDENTIALITY
Senator Boozman. Okay. And as far as we can always put
safeguards and a lot of research sometimes involves people and
things like that. I mean, we can always put the safeguards in
to protect, so that we are able to release the data without
jeopardizing people. Is that----
Dr. Collins. So, I think there, you're getting at the issue
about privacy and confidentiality for people who are part of
clinical trials that NIH supports who have been willing to
volunteer to take part in a study and who are happy to be part
of that, but don't want all of their medical records to be
accessible by everybody on the planet.
Yes, we take that with great seriousness and make every
effort, and I think we've been quite successful, to keep that
information only in the hands of those who have a need to know
as part of the research project.
Senator Boozman. Again, thank you all for being here. I
really do appreciate your efforts and, as a new member on the
panel, I look forward to working with you in the future and
supporting your efforts. Thank you.
Dr. Collins. We look forward to that, too. Thank you.
IMPACT OF THE BRAIN INITIATIVE ON NEUROLOGICAL DISORDERS
Senator Harkin. Thank you, Senator.
We'll start a second round here. I wanted to follow-up a
little bit on the BRAIN Initiative, Dr. Landis and Dr. Hodes,
because when I first heard about this bump-up in this new
initiative, we were talking about it and someone said, well,
how is this going to affect all the research on Alzheimer's? I
don't know.
There's a report that came out that said that the total
cost of care for individuals with Alzheimer's disease will soar
from $172 billion in 2010 to more than $1 trillion by 2050;
that Medicare costs are increasing more than 600 percent from
$88 billion today to $627 billion in 2050, if we keep on the
same trajectory.
So, tell me about this BRAIN Initiative. What's it going to
do in terms of the research we're doing on Alzheimer's, or is
this something separate and apart?
Dr. Landis. So, let me talk about the BRAIN Initiative and
the promise of the BRAIN Initiative, and then I'll turn it over
to Dr. Hodes to address the issue of Alzheimer's.
The long-term goal of the BRAIN Initiative is to be able to
develop treatments for patients across the broad range of
psychiatric and neurological disorders, and I'll give you a
very specific example.
In the case of Parkinson's disease, one of the major
advances has been the development of deep brain stimulation
where electrodes are planted in particular regions bilaterally
of Parkinson's patient's brains in the midcourse of the
disease.
This stimulation, kind of like a brain pacemaker, can
transform the quality of life of those patients. They can move
freely. They're much more active. They would, in some cases,
not even appear to have Parkinson's.
That effect wears off with time. This stimulation is very
crude. It's an electrode that is influencing the circuit
behavior. If we understood more about how the circuits work
that control movement, that control compulsions, that control
speech, we would be able to design much better interventions,
electroceutical interventions--not pharmaceutical, but
electroceutical--that would rebuild those circuits in a much
more effective way.
Deep brain stimulation is now being used for obsessive-
compulsive disorder. It's being used for intractable
depression. And in each case, the electrode is going in a
different part of the brain, but it's the same crude
stimulation.
So, just by analogy to Parkinson's, if we understood the
circuits for obsessive-compulsive disorder or intractable
depression, we would be able to come up with much more
effective ways to change the circuitry to ameliorate those
diseases.
IMPACT OF THE BRAIN INITIATIVE ON ALZHEIMER'S DISEASE
Senator Harkin. That's all well and good, but we have a
crisis on our hands with Alzheimer's, a real crisis. And I'm
wondering--this is well and good. I'm all for that. But I'm
concerned that we're not doing enough to really focus more
research on, if you can just put off the onset of Alzheimer's
for 5 years, that would save so much money.
So tell me how this affects Alzheimer's research?
Dr. Hodes. Thank you for the opportunity to comment on
this.
As noted, the cost, the public health and human suffering
cost of Alzheimer's, is huge. In addition to the public health
demand, of course, what is important is for us to assess
scientific opportunity and quality of science. It's one thing
to recognize a problem. Now we have a responsibility to address
it in the best possible way.
And the most responsible way to do this at this point, when
we don't know what ultimately would be the successful approach,
is to invest across a spectrum from those basic discovery on
through translation.
So, we have some enormously important and innovative
clinical trials happening. In the last year, for the first
time, we're able to identify people at enormously high genetic
risk, in whom we can find, by bio-imaging, signs of disease
years, even decades, before onset and begin for the first time
to treat them.
So, we have new opportunities we didn't have before.
But having said all this, we still have an opportunity,
and, in fact, an obligation to better understand the cellular
and molecular underpinnings, so that we can continue the effort
to generate new generations of investment. That is where this
BRAIN Initiative happens.
It's clear that Alzheimer's disease is not a disease of
just a single cell or even a single cell type. It involves
defects in the communications between cells, and the more we
understand, in the sense of what the brain will tell us, the
better we can intervene to the specific things that are going
wrong in Alzheimer's disease.
Senator Harkin. So, again, you're both telling me that this
BRAIN Initiative does have an impact on Alzheimer's research.
Dr. Landis. Yes. So, one very surprising finding of the
last couple of years has been that there is abnormal electrical
activity, almost like mini seizures in the brains of
Alzheimer's patients. It's not clear the extent to which that
abnormal activity influences the course of the disease.
But if we knew better how to modulate activity in circuits,
and which were the right circuits, we could potentially
intervene in those electroform activities in Alzheimer's
patients and potentially have a very positive effect on their
quality of life.
Dr. Hodes. It's well-described, and in fact, it comes back
to another point made, the concern we have about not being
overly conservative, that we don't fail to take advantage of
truly bold and innovative new approaches. This is an example,
at the same time we're doing the best we can to translate what
we think is the best information about cause and potential
interventions for Alzheimer's, we still have an obligation to
make sure we examine broadly the kinds of information which
will tell us about whole new approaches that may be, in the
end, the best or most definitive solution.
Senator Harkin. Thank you all very much.
Senator Moran.
CARDIOVASCULAR DISEASE
Senator Moran. Mr. Chairman, thank you.
Dr. Gibbons, cardiovascular disease is the leading cause of
death in the United States. It's certainly a driver of
healthcare expenditures. I'm told it costs the U.S. consumer,
the patient, $312.6 billion a year.
Sunday's New York Times had an article on an NIH study that
is using genetic sequencing to find factors that increase the
risk of heart disease beyond the usual suspects of high
cholesterol, high blood pressure, smoking, and diabetes.
Would you tell us more about that study?
Dr. Gibbons. Well, thank you for that question. This is one
of the great success stories, I think, in biomedical research,
where discovery science related to the pathways that determine
low density lipoprotein (LDL) cholesterol, the bad cholesterol
metabolism, led to Nobel Prizes for Brown and Goldstein.
There was a great public-private partnership that led to
the identification of a target that would lower LDL
cholesterol. That led to a drug, Statins. I suspect, for those
of us over 50, a lot of us in this room may even be on one.
That was a breakthrough drug that's transformed medicine.
Indeed, that public-private partnership is one that is critical
to advancing medicine.
The question now is that although we have studies that show
the remarkable improvements of having patients on statins,
unfortunately, there are still patients on statins who have a
heart attack every few moments in this country. So, that tells
us there's still unfinished business. There's still some
unsolved mysteries.
That article related to us continuing to try to figure out
those patients where we don't really understand all the risk
factors, all the predictors of who's going to have a heart
attack. And as you saw in that article, a devastating impact on
a whole family that we really couldn't explain, but that's
where we have these unprecedented opportunities.
With new technologies, we're able to sequence parts of the
genome and probe into why is this family so different and
distinctive in a way that's really devastating to it? We're
hopeful that that will identify new pathways that will tell us
more about the risk of heart attacks. That may recapitulate
that story we just had with LDL cholesterol.
That's the promise of the future. Those are the investments
we need to make now for those breakthroughs tomorrow.
Senator Moran. Is there enough research to give us a clue
as to what those other factors may be?
Dr. Gibbons. Well, there's a lot of promise. Perhaps one
example, a sort of a harbinger of that, relates to a molecule
called proprotein convertase subtilisin/kexin type 9 (PCSK9),
in which a similar sort of strategy delved into the molecular
determinants of, again, a group of families, a group of
patients that had an abnormal level of LDL cholesterol. The
probing use of modern genomic technologies unveiled this new
gene in this other pathway that told us another potential
target.
And indeed, as part of the recapitulation of that public-
private partnership in which discovery science translated into
drug development, a new drug has been developed that targets
that same sort of pathway. That's now in the midst of clinical
trials, to see if on top of statins or in a complementary way
going after this new target can actually give us more bang for
the buck.
Similarly, one of the things that we're learning is that
although you have that bad cholesterol, what we're also
appreciating is not just that clogging of the arteries but it's
also the activation of the body's immune system that sort of
turns against the blood vessel and inflames it just like your
allergies flare up your sinuses.
In that sense, the blood vessels were inflamed.
So, what we're now looking at is new targets that may not
only target the cholesterol level but that inflammatory
response that also promotes heart attacks. That's where some of
the great breakthroughs, I believe, are coming. And indeed,
we're funding a study that's looking at tackling that
inflammation part of the story, to see if we can make the next
breakthrough.
Senator Moran. I wish you great success.
Dr. Gibbons. Thank you.
ACCESS TO CLINICAL TRIALS
Senator Moran. Dr. Collins, I have very little time left,
but as people know, Kansas is a very rural State. I have
concerns about clinical trials.
And in order, I assume, for a clinical trial to have
validity, it takes a wide range of demographics and
characteristics. And it seems to me there are barriers toward
some people joining clinical trials based upon geography, age,
other demographic and personal characteristics, perhaps fear of
Government research, lack of awareness of clinical trial
availability.
What can I do--what is NIH doing--but what can I do as a
Senator in caring for Kansans to make certain they are aware of
the opportunity to participate in clinical trials and
potentially improve their health and save their lives?
Dr. Collins. It's a great question. NIH is by law, in our
clinical trials, required to be sure we are reaching out to a
diverse population. We track that carefully, and all the
individuals who review clinical trial grant proposals and the
program staff who follow those, make sure that we have a
diversity of population involvement in the studies, whether
it's heart disease, diabetes, cancer, whatever.
But of course, we are dependent upon public knowledge about
the ability to be part of such trials, and I appreciate your
question very much in that regard.
There is a Web site called clinicaltrials.gov, which is
heavily utilized in every clinical trial that we support. And
most of the ones supported by industry are also listed on that
site. You can search it very readily to identify a particular
condition, in some particular part of the country, where a
trial is currently enrolling patients and what's the nature of
that trial. And people can decide if they want to take part.
Getting the word out about that would be a wonderful thing
to do, and I appreciate very much your suggestion of helping
with that. We would welcome that.
Dr. Landis. If I could just add something. The National
Institute of Neurological Disorders and Stroke (NINDS) recently
set up a phase II clinical trials network called NeuroNEXT,
with 25 sites across the country. One of them is at the
University of Kansas Medical Center, and we are hoping to
incorporate into the clinical trials undertaken by that network
telemedicine, which would enable, for example, for stroke where
patients at a distance to be seen by and treatment recommended
or randomization recommended through the main NeuroNEXT site.
So we're very interested in engaging in this with you.
Senator Moran. I like that answer. Thank you very much.
Senator Harkin. I'm sure you do.
Senator Shelby.
PROGRESS OF THE PROVOCATIVE QUESTIONS INITIATIVE
Senator Shelby. Thank you, Mr. Chairman.
Dr. Varmus, last year, we discussed a new initiative that
you started to answer what we call provocative questions in
cancer research.
When budgets are constrained, we need, I believe, out-of-
the-box ideas to answer some of the big research questions that
could lead to the next breakthrough. You're in the forefront
and I think your project is an innovative approach to define
some of the unanswered questions in cancer research.
Would you share with the committee this afternoon some of
the progress you've made on this initiative, and what
provocative questions have been awarded grants, or where are
you?
Dr. Varmus. Thank you, Senator.
Obviously, this program is only a little over a year old,
so we don't have results yet, but we do have results of
advertising for applications.
The first year, we chose 24 questions, the kinds of
questions that were raised vary dramatically from questions
about why people with profound obesity have increased risk of
dying of certain kinds of cancer. There were questions about
why drugs that are not all that effective in many
circumstances, like chemotherapy for certain kinds of cancer,
are remarkably effective for testicular cancer and certain
other rare cancers.
We've asked questions about behavior. Why do people still
smoke when they know how bad smoking is?
There were 24 questions of those similar dimensions chosen.
We've received 750 applications to try to answer those
questions. All 24 questions were addressed by at least several
of the applications.
Funding is short. We were able to fund slightly over 50
applications. The funded grants address most, but not all, the
questions.
We then revised the questions, included some new ones that
had come from recent workshops. We reconfigured some questions
that we thought, perhaps, could be addressed more effectively
if we rephrase them. And we received, this year, so far,
several hundred applications.
So, there is obviously a pent-up need. How good the
applications are? It's hard to say. Many received very high
marks from the reviewers. How well they'll do, that's always a
crapshoot, frankly. And we won't know for a few years how well
this works.
We have gotten, of course, a lot of feedback from our
community. They like the idea that we're not dictating the
questions. The questions are coming from a community effort.
We're trying to support the community at a period when
morale is poor because of the low success rate. We're trying to
say, we are partners in trying to develop the kinds of
questions we think this community should answer, the kinds of
risk we should be taking. We see this as one of the ways, not
the only way, by any means, in which we try to cope with
sequestration, with reduced opportunity to get grants.
Thank you for the question.
AUTOIMMUNE DISEASE RESEARCH
Senator Shelby. Dr. Collins, I'd like to talk about
autoimmune and the research there.
The NIH and various investigators have come a long way in
dealing with autoimmune research, because it goes to the basis
of so many things. In particular, where are you today in trying
to deal with lupus? We've talked about this before and there
have been some breakthroughs there. And where do you think you
might go?
Dr. Varmus, do you want to get into that?
Dr. Varmus. No, thank you.
Senator Shelby. Okay, okay. Any of you could. Dr. Collins.
Dr. Collins. Actually, I'm going to ask Dr. Fauci to get in
on this, because he's a card-carrying immunologist, and he can
really talk about this.
Senator Shelby. Doctor, thank you very much.
Dr. Fauci. It's a pleasure. Thank you for the question. One
of the approaches that we and other institutes are taking with
regard to autoimmune diseases is making some significant
advances in the field of what we call immune tolerance.
Immune tolerance is to train the body's immune system not
to respond inappropriately against certain antigens. In the
case of lupus, those are self-antigens, and that's the reason
why they call it autoimmunity.
Several years ago, we established an immune tolerance
network that was originally established to look at ways that we
could prevent the rejection of transplants. We've expanded that
now into the study of a number of other diseases that are
clearly characterized by autoimmune phenomenon, including type
1 diabetes, certain allergies, as well as very important
rheumatologic diseases like systemic lupus erythematosus.
So, it really is, again, another, I think, beautiful
example of studying the fundamental, basic research on the
immune system that is now being translated into therapies to
suppress inappropriate immune responses.
COLLABORATION WITH INDUSTRY
Senator Shelby. Dr. Collins, do you want to talk about any
therapies that are coming along?
Dr. Collins. I appreciate the chance to respond. I just
want to mention one collaboration that's underway right now,
which is actually quite groundbreaking and, I think,
innovative. And that is something called the target validation
consortium, which is a group that has come together between
industry and NIH to try to identify amongst a wealth of new
potential drug targets that have emerged from basic science
studies, things like genomics and immunology, which are the
ones that are actually going to work, because the industry
wants to put their bets on something that's actually going to
lead to a drug that's safe and effective.
So, working with industry, we've identified four areas of
great opportunity. One of them is autoimmune diseases--
rheumatoid arthritis, lupus, Crohn's disease. The others are
type 2 diabetes, Alzheimer's disease, and schizophrenia.
And right now, we're in the midst of the design phase of
this effort with 10 companies that have agreed to sign up. This
is at the very high level with the companies in the design
phase. And, if it looks promising in the next couple of months,
we're likely to see a major new kind of collaborative effort
where industry and NIH agree that this is actually open access,
precompetitive information, we can all work on this together.
Let's find the most appropriate targets and then turn industry
loose to find that next generation of drugs.
Senator Shelby. Thank you very much.
Thank you, Mr. Chairman.
Senator Harkin. Thank you, Senator.
Senator Mikulski.
Chairwoman Mikulski. Thank you.
You know, if we just stuck with the A words, it would keep
us all very busy for three lifetimes, from arthritis to
Alzheimer's to allergies and so on.
So it's great to hear both sides of the aisle talking about
the same thing.
I want to come back to Dr. Fauci.
Senator Shelby, I was also going to raise the question of
autoimmune. I'm glad that you did.
MULTIPLE DRUG-RESISTANT BACTERIA
But I want to raise, Dr. Fauci, with you the superbug
problem, because this is a significant issue. And I'd like to
know where are we heading with our research? What are your
thoughts and recommendations? Is it also recommendations that
should be implemented in more quality initiatives in hospitals,
like the Pronovost checklist?
Could you share with us, because this is a really
significant issue that we're hearing from both constituents and
hospitals?
Dr. Fauci. You're very correct, Madam Chairwoman, that the
issue of multiple drug-resistant bacteria, and we'll just
concentrate on them now as opposed to other types of resistant
microbes, are a very important problem in the United States and
worldwide, and a growing problem.
If you look at the number, up to a million hospital-
acquired infections, of which a rather substantial proportion
of them are resistant to the standard drugs leading to the
unnecessary deaths of people in the hospital. This is a major
public health issue.
There are two approaches to that. One is a public health
approach, which really relates to some of the recommendations
of our own Centers for Disease Control and Prevention, and the
other is the basic research approach, which we at the NIH are
taking.
The public health approach is on things like isolation,
identification of people when you transfer from one hospital to
another to make sure you let people know that you're
transferring somebody with a resistant microbe. You know, we
had a problem at the NIH a-year-and-a-half ago that we luckily
solved. One of the things we learned is that you have to make
people aware of when you're dealing with a drug-resistant
microbe in a patient. Washing hands, all kinds of isolation
procedures.
But the real core problem, that we've been intensively
addressing over the last couple of years, is the lack of a
really robust pipeline of new drugs that could take the place
of the drugs that are now--to which the microbes are resistant.
So, if you look at how things work with the NIH and how we
interdigitate with industry, we generally do the fundamental
basic concepts. We make the initial discovery, proof of
principle, then maybe go into a phase I or maybe even a phase
II trial. Whereas industry, which is responsible for making the
product, generally meets us halfway or so.
The risk, economically, for a company to invest a lot of
money into the development of new antibiotics is such that we
have to help what we call de-risk them. In other words, pushing
the envelope closer to getting better understanding of
mechanisms of drug resistance, how you can target on a microbe,
new targets for drugs to make it easy for the company to get
involved in providing us with this robust pipeline.
I think that's going to be a very good approach, because
we've actually just recently established a new clinical trial
network for multiple drug resistant bacteria in our hospitals.
So again, to reiterate, it's a very serious problem, and at
the NIH, we're taking it very seriously.
Chairwoman Mikulski. Well, first of all, that's promising
to hear. And we also have to look at the role of the Centers
for Disease Control and Prevention (CDC) here.
I know, Mr. Chairman, you'll be holding a hearing on that
in a matter of days.
But, Dr. Collins, is that, I know it's not the--but is this
the methodology you're talking about where you work with the
industry on what, I used the term precompetitive, or whatever
is the right legal term. But, really because there was so much
risk in some of these areas, the private sector is not going to
get into it, and we do create our own valley of death, because
we don't go far enough. Is this one of those endeavors?
Dr. Collins. You're quite right. The valley of death in
this situation, that Tony was just describing, can be broad and
yawning because the far side of it is even further away,
because of companies' lack of really commercial motivation to
get engaged.
You develop a drug for highly resistant organism. People
will say, you shouldn't use that drug, except in very specific
circumstances. Otherwise, you'll use it up and it won't be any
good anymore. So the market is very small.
Chairwoman Mikulski. And people want cheap antibiotics,
too.
Let me get to another thing before my absolute time is up.
I know you've talked about Alzheimer's and many issues.
AUTISM
I want to talk about autism, another A word. This is really
another epidemic that has hit our family, our family of fellow
Americans.
Just about in every school, almost now in every extended
family, there is a child facing one of the aspects of the
spectrum of autism.
Could you share with us where we're heading with research
on this? Is this something we should also look at beefing up?
Could you share with us where we are on this? Whoever is
appropriate, for anyone.
Dr. Collins. I'll say one sentence, and then ask Dr. Landis
to say more.
One area that is making progress is to understand genetic
contributions to autism. We now think maybe 15 to 20 percent of
cases are the result of new misspellings in DNA that were not
present in either parent but appear in that child.
Almost always that seems to be in a pathway that involves
synapses in the brain. That seems to be the common thread here
about what's wrong in autism. The connections between nerve
cells aren't forming in the way that they normally should.
But there's much more to say here.
Dr. Landis. So, I think that is in fact one of the most
promising avenues, and there are a number of genetic studies,
which are looking at trios where the parents are normal and the
child has autism, and using advanced genetic techniques,
identifying the genes that affect the gene or genes
responsible.
What's particularly interesting is, as the number of genes
go, just as Dr. Collins said, these are genes which act on the
development of connections and the development of the synapses.
Of most interest is the fact that the same genes are being
identified in epilepsy and schizophrenia and a number of other
neurodevelopmental disorders.
It will be very important to figure out, first of all, what
those mutations do to development, but also why the phenotype
of patients, each of which has the same mutation, is so
different. So, very interesting, very interesting clues.
Dr. Collins. Just to quickly point out also that despite
the advances in genetics, we know that's not at all the whole
story. There must be profound influences that are based upon
other environmental events, some of them probably happening
during pregnancy. There's a great deal of intense effort to try
to understand that as well.
Chairwoman Mikulski. Thank you very much, and just thank
you for what you do every day. Thank all the 18,000 people at
NIH and the extramural people.
Senator Harkin. Thank you, Senator.
Senator Boozman.
INTER-AGENCY COLLABORATION
Senator Boozman. Thank you, Mr. Chairman.
Dr. Collins, I'd like to ask about, and really use two very
different examples, about the ability of NIH to perhaps work
with the other agencies.
I'm on the Veterans Affairs Committee. Everybody at the
panel here is very, very concerned about veteran suicide.
They're working really hard to try and do something under a lot
of pressure to perform.
One of my concerns is the easiest thing to do, if you have
a caseload that is bigger than you can handle, there is a
tendency to overmedicate. I think that is a problem.
But aside from that, again, the ability of your agency to
come in, recognizing there is a problem. They're spending a lot
of money in trying to solve the problem.
If there's an effort that we could collaborate, and you all
use the unique expertise that you have to help with that
problem.
The other thing is I was at the toxicological lab in Pine
Bluff of the FDA. And another very differing example is the
nanotechnology, which the FDA is concerned about, we're all
concerned about. What really helped me grasp it was the fact,
when you look up, you can think of infinite upness. With
nanotechnology, you're really dealing with infinite smallness,
which is amazing.
And as you guys know better than anyone, as you get very
small, then everything changes.
But it is something that offers tremendous potential. One
of these things that truly can change the world by helping us
not use as much resources by better lubrication, things like
that where things don't wear out, these conflict minerals and
things.
So is there the ability for you all to step in and help FDA
deal with those kinds of problems and support the work at the
toxicological lab?
Dr. Collins. Senator, those are two terrific questions.
With regard to suicide, I think all of us are deeply
concerned to see what the rates are of suicide, especially in
returning servicemen. We've been working, actually, closely
with the Department of Defense in a program called Study To
Access Risk and Resilience in Servicemembers (Army STARRS),
which has enrolled more than 100,000 recruits, trying to
identify what, if any, kind of warning signs have been missed
in the past that could give us a better chance to intervene
before suicide occurs.
This is a close collaboration between our National
Institute on Mental Health (NIMH) and the Department of
Defense. And there is an interaction there also with the
Department of Veterans Affairs (VA) because of their very
strong interest in the same issue.
With regard to your question about toxicology----
Senator Boozman. I'm sorry, the next step again would be
dealing with people that are actually at that point.
Dr. Collins. Yes.
Senator Boozman. That might be helpful also.
Dr. Collins. Indeed. And of course, suicides are more
common than homicides in this country, and there is a great
deal of effort to try to understand ways to identify risks.
Obviously, for people who have not been in the military, if
you look at what are the risk factors for suicide, bipolar
illness is a very major correlate, because when people with
that condition go into a deep depression, that is often where
the risk is highest.
Senator Boozman. And heavily medicating in some cases makes
it worse or better?
Dr. Collins. I think the experience has been that proper
medication, with Lithium and other efforts, can be lifesaving.
Reading books by Kay Jamison, for instance, would emphasize
that, as someone who has written about it and who has
experienced it herself.
But there are challenges in terms of getting it just right,
and we are still working on new interventions that will be more
effective than what's currently available, because most of the
drugs have been around quite a long time, and it's time to see
if we could find some new answers. This notion of working with
industry to find new targets comes to mind.
With regard to your question about toxicology and
nanotechnology, Peggy Hamburg, who's the commissioner of the
FDA and I jointly run a leadership council that tries to
identify ways that our agencies can work closely together,
particularly helping FDA with identifying new regulatory
science opportunities, and FDA helping NIH identify areas where
more science is needed and where our investigators can be
better prepared to conduct trials that FDA can then review.
Nanotechnology is a very interesting example, because there
is a question about the safety of nanotechnology applications
for human health. Given that this isn't exactly a simple area,
all different particle sizes, all different kinds of compound
constitution, NIEHS, the National Institute of Environmental
Health Sciences, has a research program on this. And we are
part of the National Nanotechnology Initiative.
We mentioned earlier the BRAIN Initiative, trying to come
up with ways that could sample these 86 billion neurons. If
we're going to get anywhere near that, we're going to need
nanotechnology tools to do so. So, it is very much an
appropriate question. To be sure, we're working together.
Senator Boozman. Thank you, and again, thanks for all you
do.
NIH/CDC/FDA COLLABORATION ON H7N9 (AVIAN FLU)
Senator Harkin. The last question Senator Mikulski asked, I
think Dr. Fauci, the question about the superbugs. One last
thing was that in meeting with Dr. Frieden of the Centers for
Disease Control and Prevention a few days ago, talking about
this new avian flu.
You've been down that road before, Dr. Fauci.
So, a new one has popped up. This one is known as H7N9, and
there have been 131 confirmed cases by the World Health
Organization (WHO), 32 deaths. There has been no evidence of
sustained human-to-human transmission.
But the problem is, as I understand it, that there is
obviously a very high death rate, but the birds that are
infected have no symptoms. And so again, how are you
correlating research on this along with the CDC?
Dr. Fauci. Thank you for that question. It's a very good
example of very nice collaboration and coordination between the
different agencies of HHS, not only CDC and NIH, but also FDA.
So, where we are right now, there are actually 35 deaths.
There were three deaths that were reported yesterday and today.
So it's 131 cases and 35 deaths.
We are approaching this exactly the same way as we
approached the H5N1 that started in 2003 that we discussed
before this committee many times that's still smoldering, as
well as the 2009 H1N1 real pandemic that we had. That is
virtually within days of noticing this, the virus was isolated,
sequenced, sent to the CDC with the sequence, who are then, by
reverse genetics, created what we call seed viruses for the
development of a vaccine.
A seed virus is a virus that we make that we can then
distribute to the different pharmaceutical companies that we
have contractual relationships with for our regular seasonal
flu. They are already starting to make what we called pilot
lots to determine whether or not we're going to be able to test
these.
The NIH, which is our main responsibility, has already
developed and designed clinical protocols to test what is the
right dose, do you need an adjuvant or not, do the doses differ
between children, adults, elderly, and pregnant women. I've
seen the trial designs and they are ready to go. As soon as the
pilot lots are up, which will likely be by the end of June, the
beginning of July, we'll start clinical trials.
Now, we may not ever have to use the vaccine. But the
important thing is, we'll get those lots, we'll know how to use
it. So, if it does begin to have what you mentioned correctly,
sustained human-to-human transmissibility, which it does not
have right now, if it does, then we can scale up and have a
vaccine available.
We've also done many of the sequencing to look for genes
that might predict whether it's sensitive or resistant to the
neuraminidase inhibitors, the ones we commonly use, Tamiflu and
Relenza. Fortunately, they appear to still be sensitive to
those antivirals.
UNIVERSAL INFLUENZA VACCINE
Dr. Collins. So, Tony, wouldn't it be great if you didn't
have to do this every time a new strain appeared? Do you want
to say something about progress to get a universal influenza
vaccine, because that's quite exciting? We might not have to
have this conversation in 10 or 15 years.
Senator Harkin. How close are we to that?
Dr. Fauci. Well, you know, I can't give you a time, but I
can tell you we're clearly closer than we were a year or two
ago, and let me explain why. Because, what Francis is alluding
to, for people who didn't hear it, is the universal flu vaccine
that you could actually give to someone and then it would be
inducing protection against a wide range of influenza strains,
from season to season, and even from pandemic to pandemic.
What was discovered a few years ago by NIH grantees, that
there's a part of the protein that's the main protein of
influenza called hemagglutinin that is shielded from the immune
system recognizing it.
So, when you get infected, Mr. Chairman, or you get a
vaccine every year, your body's immune system doesn't recognize
a part of that protein that doesn't change from strain to
strain. The part that changes is called, well it looks like a
mushroom, it's got a head and it's got a stalk. The part that's
the protective part is the head, and it changes from season to
season. And when you have a pandemic, it changes a lot.
So, if you make an immune response, you're good for that
season, but you're not good for the next season when it
changes. Whereas on the stalk of the hemagglutinin, there is a
sequence, a particular protein, that doesn't change from flu to
flu. So, we've now figured out a way, how to show the immune
system that particular protein, so that it makes an immune
response against it. We've now shown it in animals, mice,
ferrets, and monkeys, that when you show them this protein,
they make antibodies against the wide array of influenzas.
We started phase I trials, showing that it's safe, and it
induces a response. We're getting ready to go into a phase II
trial.
So, I can't give you a year when we're going to have it,
but we're a heck of a lot closer than the last time you asked
me that question.
Senator Harkin. I had no idea of that. That's pretty
encouraging. I mean, just think of the health implications.
Dr. Fauci. That would be enormous.
Senator Harkin. It would be huge.
Dr. Fauci. Right.
Senator Harkin. And the savings in illnesses, the
hospitalizations, loss of work, my goodness, plus just knowing
that you're safe against some of these pandemic flus.
Dr. Fauci. And you could stockpile. See, that's the thing
that we can't do. We're always in a yearly race. We find out
what's going to be circulating, and we race to make a vaccine
to be ready in the fall to give to people, so they can have it
for the winter.
If you have a universal flu vaccine that essentially covers
it all, you can start making it right now for 2 years from now.
Senator Harkin. Of course. Keep us informed.
Dr. Fauci. I will.
Senator Harkin. That's very encouraging. Especially if
you've got something that you know dosage-wise you can do for
children, adults, pregnant women, all the different types of
people that need this type of a vaccine.
Dr. Fauci. So, when you come to the NIH, we'll show you
where it's done.
Senator Harkin. I will, thank you. That's very encouraging.
Senator Moran.
EXPERIENCED AND NEW INVESTIGATOR FUNDING
Senator Moran. Mr. Chairman, thank you.
Just a brief question, Dr. Collins. I'd like to have you
assure me that there are actions in place that make certain
that both well-established investigators are funded as well as
incubator-type environments where young investigators can
thrive and provide great breakthroughs.
Dr. Collins. Of course, that's very important. It could
hardly be more important.
I think the most important resource we have is the talented
scientists who do the work, and some of them are in mid-career
and just incredibly at the top of their game, and others just
getting started with vision and drive and energy.
The sad story is that all of those groups are taking a hit
right now. There's nobody getting protected.
We do what we can, particularly with early stage
investigators to be sure they have a chance to get started. So,
we have them, in the way we do our peer review, compete against
each other. The early stage investigators, they don't have to
compete in the same pool as far as funding decisions with
somebody who already has an established lab and a lot of
preliminary data and a lot of publications, because we want to
be sure that we're not disadvantaging our future, which are
these folks that are just getting started.
But there is no magic here when success rates have fallen
for everybody to 15, 16 percent. I know we are losing
significant talent all through the career range of the people
that we support, from the young to the middle, to those who are
basically in the cap of their career.
DECLINE IN THE NUMBER OF NEW INVESTIGATORS
Senator Moran. You have the statistics--I've never seen you
not be able to answer a question, so I know you have the
statistics. Are the numbers of new applicants, individuals who
have never applied, or organizations that have never applied
for a grant, is that number changing?
Dr. Collins. You know, I'm a little concerned to see that
this year, the numbers seem to be dropping back a bit, and
that's actually quite troubling. That begins to suggest that
people are beginning to lose hope. And you can sort of see why.
When investigators, with this success rate of 15 or 16
percent, spend most of their time just writing a grant only to
have it rejected, but then they'd better be writing another
one, otherwise, their lab is going to close.
They don't get to do science that much anymore. It's all
about trying to find the funding from the Government, from
foundations. I think, after a while, as people begin to burn
out with that, perhaps we are seeing a fall off in the
willingness to go through that experience over and over again
only to see rejection.
So, I am concerned, as one of the warning signs that the
community is beginning to be sufficiently disheartened as we're
going to lose people.
We have lots of anecdotes about that. It's hard to collect
precise data about exactly how many investigators have given
up. We're in the process of trying to do that, but the
anecdotes are sufficiently numerous that I'm deeply worried.
Senator Moran. Well, Doctor, I would never contradict you,
but I find this hearing always a place of hope. And it is one
of the places within the halls of Congress in which, when you
leave the hearing, you have a better outlook for what the
future holds.
And so I appreciate very much what you and your team, what
the folks at NIH and those that you fund and support, provide
something that America desperately needs, something called
hope.
And I just would encourage you to let Dina Faddah know that
there is hope, and tell her that we all encourage her to pursue
that career in research and science and medicine. And that
while there's always challenges, the opportunity to provide
hope to Americans, to provide hope to the world, it's worth the
battle. And we look forward to being allies with her in that
effort to see that hope continues.
Dr. Collins. Senator, that's wonderful, and I will
personally pass that word of encouragement to her.
Senator Moran. Thank you.
Senator Harkin. Thank you, Senator.
Senator Shelby.
VETERAN SUICIDE
Senator Shelby. I want to follow up on the troubling
information we have about so many veterans committing suicide
when they come back from Iraq or Afghanistan, and the
devastation it does to the families, to the society and so
forth.
My question is this, I don't know if you have it, I don't
know if the VA has it or DOD, but are there statistics, say,
going back to the end of the Second World War, about the number
of veterans coming back, the number of suicides per thousand,
the Korean war, the Vietnam war, the conflict in Iraq and so
forth. Because that would be very troubling, yes, but maybe
informative, too, to a point.
Do you know if they have those statistics, Doctor?
Dr. Collins. I'm sure there are such statistics. I don't
have them at my fingertips. And of course, one would have to
look at the statistics with some caution in the fact that in
the past, anyway, oftentimes suicides were not reported as
suicide, because of the stigma attached to that. So, it could
well be that one looks at those and it looks as if----
Senator Shelby. That could be skewed.
Dr. Collins. Yes, they would be skewed, particularly in the
past and probably still in the present, where suicides, because
they do carry for families----
Senator Shelby. Soldiers go through this awful stress in
combat.
But as a society, we need to figure out how to prevent it,
don't we?
Dr. Collins. I totally agree with you. And again, I think
if Dr. Tom Insel were on this panel, who is the director of the
National Institute of Mental Health (NIMH), he would
immediately put forward to you a number of things that our
Mental Health Institute is trying to do in terms of identifying
risk factors and interventions, figuring out how this fits
together with things like traumatic brain injury and post-
traumatic stress disorder (PTSD).
Senator Shelby. Thank you very much.
Thank you, Mr. Chairman.
Dr. Landis. I think one of the differences between Iraq,
Afghanistan, or in earlier wars are the improvised explosive
devices with significant repeated mild traumatic brain injury.
There's evidence that it's an invisible wound, and soldiers
often don't recognize that this has been an issue and don't
seek appropriate help.
So, I think that the statistics for these wars might be
different than previous wars.
Senator Shelby. One added dimension, I just thought of it,
because so many of our soldiers have had multiple tours--some
volunteered, some didn't, in all this--which puts a lot of
stress on them and their families.
Maybe there are studies into that, too, say one tour, two
tours, three tours, and dramatic effects.
Dr. Collins. Yes, I'm quite sure that data has been looked
at by the Department of Defense and is part of the effort as
we're identifying risk factors in this STARRS study that ought
to be looked at very carefully. And if there is some indication
that the number of tours is a factor, obviously one would want
to intervene in a prospective way to try to provide that kind
of support that apparently is not currently sufficient.
FUNDING THE FUTURE OF NIH
Senator Harkin. Thank you, Senator Shelby.
Well, again I want to thank you all for your dedicated
public service, your leadership in health.
It's been my privilege and pleasure to have either chaired
or been the ranking member of this subcommittee since 1989. So
I worked with some of you for a long time.
And every time we have you all up here for NIH, again, it's
just again a reminder, I think to all of us, that there's just
certain things we can't back down from. We made so many great
strides in health research, keeping people healthy, their
cancer rates. Everything else has been phenomenal, especially
in childhood leukemia. It's been remarkable.
And with the Human Genome Project, we now have some keys
that we've never had before, the new technologies that we have
that we can use now. It just seems that this is the time to
redouble our efforts to increase significantly the funding for
NIH.
How do you do that? Well, there seems to be an attitude,
I'm not saying anybody in particular, that we want something
for nothing. If you want the best, it costs something, in terms
of the best scientists, the best brains, the best technologies,
the best equipment. We've always been the best in biomedical
research in this country.
I'm afraid that we are falling way behind, so we've got to
find sources of funding.
Back in the early 1990s, Senator Mark Hatfield was the
chair of this committee. And I was ranking member at that time,
and he was on this subcommittee. This was one of his devotions
as it is Senator Mikulski's now.
And we came up with a proposal. I don't know if it was his
idea or my idea.
But the basis of it was this, that when you buy a drug,
when you go out to your pharmacy and you buy a drug today, some
of that money goes for research. But when you buy a health
insurance policy, none of that goes for health research.
So our idea then, and this was about the time, I think,
when we're working on the Clinton proposed health bill and
stuff like that, we came up with a proposal, Hatfield and
Harkin, and that was to have every health insurance policy that
you would have a certain amount, percentage of each one that
would then go to the NIH.
It would come through this committee. And it was only just
a few cents, a couple, 2 or 3 cents, I think, on the dollar.
And then someone pointed out, well, but if you do that,
then that would just supplant what you're doing on the
discretionary money. So, okay, what we'll do is we'll say,
okay, it will go into like a trust fund for NIH, but it can
only be accessed as long as the Congress appropriates at a
minimum what they did last year, plus an inflation factor.
Dr. Fauci. That's a good idea.
Senator Harkin. Well, yes, thank you.
Well, we tried. We kind of pushed that along for a while.
We got some pushback, obviously, from the health insurance
industry, I understand that, and others.
But then that whole thing sort of faded out and nothing was
done on it.
Now with this new healthcare system, Obamacare, coming
along, there's going to be 35 million more people having health
insurance policies in this country. Some of them subsidized by
the Government, others not.
I just wonder if it's not time. I ask my friends here to
revisit this and to think about some new source of funding like
that.
Yes, the ultimate payer will always be that individual
person out there, because their health insurance payment will
go up a little, 2 or 3 cents on the dollar. But they'll have
the satisfaction of knowing that little increase is going to go
for only one thing. That's NIH research.
It can't go anywhere else, and it can only go as long as
Congress appropriates what we did last year plus an inflation
factor.
Somehow, we've got to come up with this funding. Anybody
else got a better idea, the door is open. I am willing to look
at anything. If anybody's got a better idea, let me know about
it.
Senator Shelby. Mr. Chairman?
Senator Harkin. Yes.
Senator Shelby. Did you do some work as to how much money
that would raise?
Senator Harkin. Oh, yes. It was quite significant.
Senator Shelby. It would help a lot?
Senator Harkin. Oh, big time. And it was just a couple of
cents on the dollar, was all, when you think about it. And now
we're going to have a lot more heath insurance policies out
there.
And I talked to some of my health insurance carriers, and
we have a lot of health insurance carriers out there.
Well, you know, I suppose they could live with it, but it
wasn't high on their agenda. But again, it's just something I
think we ought to roll around.
And like I said, anybody else here in the audience or
anybody else listening got any better ideas, let me know.
But we've got to get more funding for NIH. We can't
continue to go down this road. I got 20 months left here, 19
months left here. I'd like to see this turned around.
ADDITIONAL COMMITTEE QUESTIONS
Obviously, I'd like to see us start the doubling process
again, but that won't happen. I understand that. But finding a
new source of dedicated revenue that will be there and that we
know will be there year after year after year, that's got to
happen so that these young researchers, the one you're talking
about, it's nice to give her a pat on the back and say follow
your dreams. Yes, I back up what Jerry said on that.
But there's got to be something there to make sure that
those dreams are realizable, and that funding has to be there.
So, yes. Then we need to go on, but I just think this is
something we've just got to address.
So the record will remain open for 7 days for additional
statements or questions for the record.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted to Dr. Francis S. Collins
Questions Submitted by Senator Tom Harkin
Question. Dr. Collins, last month was the 10th anniversary of the
completion of the Human Genome Project, which you led and, I'm happy to
say, came in ahead of schedule and under budget. What have we learned
from this effort and where are we going?
Answer. To gain perspective about how the field of genomics has
advanced since the Human Genome Project (HGP), it is illustrative to
compare the ``state-of-the-art'' at the beginning of the HGP in 1990,
at its completion in 2003, and now, in 2013. For instance, during the
HGP, it took 6-8 years of active sequencing and approximately $1
billion to generate that first reference sequence of the human genome.
In 2003, that same feat would have still required 3-4 months and $10-50
million. But today, a human genome can be sequenced in approximately 1-
2 days for a mere $3-5 thousand. As the time and cost of human genome
sequencing have plummeted, the power of genomic strategies and the
volume of generated genomic data have increased profoundly.
This capacity to generate more data through improved and less
expensive technologies has enabled researchers to interrogate genome
structure and function and learn how the genome contributes to health
and disease. For example, in 1990, we knew of approximately 50 genes
that, when mutated, caused a human disease; in 2003 that number was
almost 1,500; and today, it is nearly 3,000. Further, knowledge about
the genomic bases for our different responses to medications--an area
of science called pharmacogenomics--also has grown steadily. In 1990,
only four Food and Drug Administration (FDA)-approved drugs required
labels that pointed out the relevance of a patient's genomic makeup for
that medication; by 2003, that number had increased to 46; and today,
it stands at 106. In fact, genomic contributions to medical research
have been so substantial that fully half of ``Time'' magazine's ``Top
10 Medical Breakthroughs in 2012'' reflected genomics accomplishments,
and these were in large part supported and/or facilitated by National
Human Genome Research Institute (NHGRI) research programs.
During the last decade, building on the discoveries of the HGP, we
have learned much more about how the genome functions and how genomes
differ from person to person. For instance, in 2012, the ENCyclopedia
of DNA Elements (ENCODE) project funded by NHGRI published a landmark
series of papers reporting a catalog of functional elements within the
human genome. The ENCODE catalog is like a GPS map for the human
genome--just as by zooming in on a GPS map of the United States (to
find the location of points of interests like banks and gas stations),
the ENCODE catalog is now routinely used by researchers worldwide to
zoom in on regions of interest in the human genome that are important
for their studies.
Meanwhile, the 1000 Genomes Project, funded in part by NHGRI, has
led to a much greater understanding of the variation among human
genomes. By sequencing the genomes of more than 2600 individuals from
different populations across the world, the project is identifying
patterns of variation between individuals and populations that will
help advance understanding of the genetic factors contributing to many
common diseases. To date, the 1000 Genomes Project data have been used
in published research studies focused on autism, Alzheimer's disease,
cancer, cardiovascular disease, and cirrhosis.
The field of genomics is now focusing increasingly on the links
between genomic variation and disease--and how that knowledge can be
applied clinically. Genomic medicine is being used to advance certain
medical specialties such as oncology, where genomics-based diagnostic
methods are increasingly being used for cancer screening and for
guiding treatment strategies. Examples include the widespread use of
``BRCA'' testing in patients with familial risk factors for breast and
ovarian cancer, the use of testing to predict breast cancer recurrence,
and the use of genomic diagnostic tests to determine the suitability of
particular therapeutic treatments. Findings being generated through the
work of The Cancer Genome Atlas--a research program co-funded by NHGRI
and the National Cancer Institute--are confirming that cancers that
appear to be morphologically similar can be separated into distinct
subtypes based on genomic information, thereby informing the choice of
therapies. Establishing the specific mutations that drive the growth of
a patient's tumor can prevent the needless and costly use of harsh
chemotherapeutic drugs that are ineffective for that tumor subtype.
From less complex diagnostic tests that predict the effect of
trastuzumab (Herceptin) use in breast cancer, vemurafenib (Zelboraf)
use in melanoma, or crizotinib (Xalkori) use in lung cancer, to more
advanced strategies of sequencing a tumor's mutated genome as a means
to guide treatment, genomic medicine is becoming a powerful tool for
guiding clinical care.
Beyond cancer, genomics is also fueling major strides in other
clinical areas. For instance, National Institutes of Health's (NIH)
Intramural Undiagnosed Diseases Program applies genomic analyses to
cases where a diagnosis has proven elusive to medical experts. To date,
through the program, two new diseases have been discovered, and 50
patients have received long-sought diagnoses. Similar approaches using
genome sequencing to diagnose rare diseases have been used in Wisconsin
(Nic Volker) \1\ and California (Noah and Alexis Beery),\2\ resulting
in life-altering treatments for the affected patients. Beyond
applications for disease identification or categorization, a promising
study at Stanford University showed that DNA sequencing could be used
to monitor organ transplant recipients non-invasively to detect early
signs of rejection. Another study, also conducted at Stanford
University, used genomics to screen a library of existing FDA-approved
drugs to determine whether they might be repurposed for use in other
diseases. Through this work, the possibility of repurposing an epilepsy
drug for use in ulcerative colitis and Crohn's disease, and using an
anti-ulcer drug to treat certain forms of lung cancer, has been
highlighted.
It is worth noting that although the primary aim of the HGP was to
improve health, the project's effects have not, and will not, be
confined to the clinic. A report by Battelle Technology Partnership
Practice (Battelle) published in 2011 showed that the HGP has had a
very positive impact on the United States economy.\3\ Specifically, the
report estimates that between 1988 and 2010, Federal investment in
genomic research generated an economic impact of $796 billion,
particularly impressive considering that HGP spending between 1990 and
2003 was only $3.8 billion. The report further found that in 2010, the
genomic sector directly supported more than 51,000 jobs, indirectly
supported more than 310,000 jobs, created $20 billion in personal
income, added $67 billion to the United States economy, generated more
than $3.7 billion in Federal taxes, and generated more than $2.3
billion in State and local taxes. An updated report is being published
by Battelle on June 12th.
---------------------------------------------------------------------------
\1\ See: http://www.jsonline.com/features/health/111224104.html.
\2\ Bainbridge MN et al. ``Sci. Trans. Med'', June 15, 2011 Whole-
Genome Sequencing for Optimized Patient Management. http://
www.ncbi.nlm.nih.gov/pubmed/21677200.
\3\ Tripp, S. ``Economic Impact of the Human Genome Project''
(Battelle Technology Partnership Practice: 2011).
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Question. Dr. Collins, a Council of Councils working group recently
recommended that NIH retire all but 50 chimpanzees to a sanctuary, in
response to an Institute of Medicine report on research involving
chimpanzees. Are you likely to accept that recommendation? If not, why
not? Are there any issues or road blocks to moving the chimpanzees?
Answer. On January 22, 2013, a working group of the Council of
Councils presented its report to the Council on the Use of Chimpanzees
in NIH-Supported Research. The report recommended that, among other
things, ``The majority of NIH-owned chimpanzees should be designated
for retirement and transferred to the Federal sanctuary system'' and
that ``A small population of chimpanzees [approximately 50] should be
maintained for future potential research. . . .'' The same day, the
Council of Councils accepted these and 26 additional Working Group
recommendations, and transmitted them to NIH for consideration. NIH
subsequently issued a request for comments and, after considering the
public comments, accepted most of the Council recommendations on June
26, 2013.
With respect to the recommendation that advises that NIH retire the
majority of NIH-owned chimpanzees, a vast majority of the commenters
agreed with this recommendation. However, a number of commenters noted
that the funding limits of the Chimpanzee Health Improvement
Maintenance and Protection (CHIMP) Act of 2000 may affect the agency's
decisions about retiring chimpanzees no longer needed for research. The
CHIMP Act amended the Public Health Service Act to establish and
maintain a system of sanctuaries for the lifetime care of chimpanzees
that were used in research that the Health and Human Services (HHS)
Secretary (through NIH) designates as no longer needed for research.
Prior to accepting the Council recommendation, there were already 219
chimpanzees living in, or were scheduled to be relocated to, the
Federal sanctuary system. Three-hundred sixty (360) additional NIH-
owned chimpanzees are not retired and reside outside the sanctuary
system.
Despite overwhelming public support to retire most NIH-owned
chimpanzees, three issues need to be addressed before NIH could fully
implement the recommendation to retire the majority of NIH-owned
chimpanzees: (1) restrictions on funding levels in the CHIMP Act (often
referred to as the cap), (2) lack of capacity in the Federal sanctuary
system, and (3) limits in authority to manage the sanctuary system.
FUNDING RESTRICTIONS IN THE CHIMPANZEE HEALTH IMPROVEMENT MAINTENANCE
AND PROTECTION ACT
The CHIMP Act authorized HHS to establish the sanctuary system but
includes a technical provision that currently limits the amount of its
financial resources that HHS (through NIH) can provide for: (1) care
and maintenance of the chimpanzees within the Federal sanctuary system;
and (2) construction to establish the system. NIH believes that its
authority to use appropriated monies to fund the Federal sanctuary
system expires once the funds spent for the operation and establishment
of the sanctuary system reach $30 million. As of February 2013, NIH had
spent over $29 million in Federal funding on the sanctuary system and
expects to reach $30 million early in fiscal year 2014. After that, HHS
may lack the authority under the CHIMP Act to obligate additional
funding to the Federal sanctuary system for care and maintenance of the
chimpanzees within the Federal sanctuary system as well as future
construction to expand the system. General Provision language has been
proposed in the fiscal year 2014 President's budget request to remove
this restriction.
CAPACITY
The agency agrees that the majority of chimpanzees that NIH owns
could be eligible for retirement but additional capacity in the Federal
sanctuary system is needed. Although the contractor (Chimp Haven, Inc.)
that maintains the Federal sanctuary system plans to use private
funding to construct additional space to house 110 chimpanzees from the
New Iberia Research Center, these new areas will not be sufficient to
accommodate the majority of NIH-owned chimpanzees that the Council
recommended retiring. NIH is currently unable to support construction
at the sanctuary due to funding restrictions in the CHIMP Act. Without
additional construction or the authority to support such work
financially, NIH understands that the Federal sanctuary system will be
unable to accept additional chimpanzees until the current sanctuary
population declines.
LIMITS IN AUTHORITY TO MANAGE THE FEDERAL SANCTUARY SYSTEM
NIH believes the CHIMP Act also limits the HHS Secretary's
authority to expand the Federal sanctuary system by adding additional
compliant retirement facilities. Currently, the system is composed of
only one sanctuary that is now at capacity, but several facilities have
approached the agency with an interest in accommodating retired
chimpanzees. NIH would like to consider additional facilities to add to
the system so long as they conform to CHIMP Act requirements and the
implementing of sanctuary regulations.
To add additional sanctuaries to the Federal system, the CHIMP Act
requires the HHS Secretary to seek approval from the Board of Directors
that oversees the nonprofit entity that runs the Federal sanctuary
system. This provision, consequently, could limit the Secretary's
ability to retire chimpanzees to other potentially compliant retirement
facilities that could provide a cost savings or less expensive option.
HHS believes it should be able to retire chimpanzees directly to other
facilities if the Secretary determines the criteria in the law are met.
We would like to point out that it would not incur additional costs to
retire chimpanzees into an expanded sanctuary system. Funds to support
their care in the research facilities could be transferred for their
care in the sanctuary system. Alternatively research facilities could
be modified to qualify for participation in the Federal sanctuary
system. Although NIH agrees that the majority of its chimpanzees could
be designated for retirement and transferred to the Federal sanctuary
system, NIH is not in a position at this time to implement the
recommendation.
______
Questions Submitted by Senator Mary L. Landrieu
Question. A year ago, our Nation adopted a National Plan that set
as goal one treating and effectively preventing Alzheimer's disease by
2025. This plan was required under the National Alzheimer's Project
Act, bipartisan legislation approved unanimously by Congress in 2010.
Achieving this goal will not be easy. In the past several months, at
least three industry trials testing potential therapies for Alzheimer's
have reported disappointing phase 3 study results.
Based on what you know today, how confident are you that the Nation
will achieve the 2025 goal of preventing and treating Alzheimer's
disease?
Answer. The identification and development of interventions that
will prevent or treat Alzheimer's disease have proven to be extremely
challenging, and it is still not possible to predict with certainty
when an effective treatment or preventive intervention will be
available. However, we have greater reason than ever before to be
optimistic.
Our efforts have been significantly advanced by recent
breakthroughs in biomedical imaging that are enabling us to identify
and track the earliest pathological stages of the disease process, long
before clinical symptoms are apparent. These discoveries, in addition
to discovery of other early biomarkers of the Alzheimer's disease
process, have opened a ``window of opportunity'' for us to target and
potentially reverse the disease's underlying pathology before
cognitive, behavioral, and emotional symptoms appear. National
Institutes of Health (NIH) has begun to launch its first such clinical
trials in presymptomatic individuals. For example, in one high-profile
study, investigators are studying whether an antibody treatment,
crenezumab, which is designed to bind to and possibly clear away
abnormal amounts of amyloid protein in the brains of people with
Alzheimer's, can prevent decline in cognitive function. Crenezumab is
being tested among members of a unique and large family population in
Colombia sharing a genetic mutation known to cause observable signs of
Alzheimer's disease at around age 45, along with a smaller number of
U.S. participants ages 30 and older. We anticipate initial results from
this groundbreaking study by 2017.
NIH also supports more than 35 Alzheimer's disease clinical trials,
including a number of studies of interventions to slow disease
progression among individuals who are already showing symptoms. More
than 40 compounds are currently under study to stimulate and advance
research on the discovery and development of new preventive and
therapeutic interventions for Alzheimer's disease (AD), mild cognitive
impairment, and age-related cognitive decline.
Question. What level of funding for Alzheimer's research at the NIH
do you think is needed to maximize our chances of achieving this goal,
and what other measures can our Nation take, recognizing these fiscally
challenging times, to stop this disease?
Answer. NIH has made one-time internal re-allocations to the
Alzheimer's disease budget in fiscal year 2012 ($50 million) and fiscal
year 2013 ($40 million) that have made it possible to develop new
opportunities in critical priority areas. Sustained availability of
funds, as indicated in the fiscal year 2014 President's budget request,
would further facilitate targeted initiatives in high-priority research
areas. Under the fiscal year 2014 President's budget request, NIH
currently estimates it would spend a total of $562 million on
Alzheimer's disease research.
In the current challenging budget climate, we are continuing to
take a number of steps to leverage our resources to the maximum extent
possible. For example:
--We have developed a rigorous and inclusive process for soliciting
expert advice on research priorities, most notably through the
May 2012 Alzheimer's Disease Research Summit, at which
internationally recognized experts in the field met to
formulate an integrated multidisciplinary research agenda that
will accelerate the development of successful therapies for AD
across the disease continuum. Summit participants also
identified the types of resources/infrastructure and new public
private partnerships that will be necessary to successfully
implement this research agenda.
--We have created the International Alzheimer's Disease Research
Portfolio, a unique database of nationally/internationally
funded AD research, which will enable organizations around the
world to coordinate funding strategies and leverage resources
in order to maximize the impact on public health and avoid
duplication of effort and inefficiency.
--We have conducted an in-depth analysis of the NIH Alzheimer's
disease research portfolio and tied specific milestones to the
goals of the National Plan to Address Alzheimer's Disease.
--Where appropriate, we are coordinating efforts with private funders
and advocacy organizations and actively pursuing public-private
and international partnerships.
Question. With respect to the level of funding at the NIH for
Alzheimer's disease, I would like for you to address what appears to be
an unacceptable gap between the growing costs of this disease to the
Nation and the amount of our Federal investment. More than 5 million
Americans are estimated to be suffering from Alzheimer's disease, a
number that is expected to more than triple by 2050. If the prevalence
and trajectory of the disease remains unchanged, the total costs
associated with Alzheimer's disease will near or exceed $1 trillion
annually by mid-century.
Answer. In fiscal year 2012, the total NIH expenditure for
Alzheimer's disease research was approximately $503 million, an
increase of approximately $55 million, or 12 percent over fiscal year
2011. This reflected a one-time $50 million increase allocated to NIH
Alzheimer's research for fiscal year 2012. In fiscal year 2013, NIH is
also allocating $40 million of funds within the Office of the
Director's budget to Alzheimer's research. For the fiscal year 2014
President's budget, NIH estimates it will spend a total of $562 million
on research related to this disease.
It is important to recognize that while Alzheimer's research
continues to be of tremendous importance to NIH, it is one of a number
of highly compelling priorities that include research on diabetes,
heart disease, cancer, mental illness, as well as cross-cutting
research affecting discovery in multiple disease areas. NIH maintains a
careful, rigorous, and ongoing planning and priority-setting processes
to ensure an appropriate balance of resources in basic, clinical, and
translational research, with the ultimate goal of safeguarding the
health and well-being of all Americans.
Question. A recent RAND Corporation study published in the New
England Journal of Medicine estimates that the direct healthcare costs
associated with Alzheimer's disease are $109 billion annually,
exceeding the direct care costs associated with cancer and heart
disease. When costs of informal caregiving are factored in, annual
costs of Alzheimer's and dementia skyrocket and are estimated today to
be as high as $215 billion annually. Alzheimer's is the most expensive
disease to American families and taxpayers--more expensive than HIV
AIDS, Heart Disease and Cancer. Despite the recognized scope of this
crisis, NIH is spending approximately $480 Million on Alzheimer's
research
How do you explain this disparity between the growing societal
burden and economic threat posed by Alzheimer's and the very small
investment we are making at the NIH in Alzheimer's research?
Answer. In fiscal year 2012, the total NIH expenditure for
Alzheimer's disease research was approximately $503 million, an
increase of approximately $55 million over fiscal year 2011. This
reflected a one-time $50 million increase allocated to NIH Alzheimer's
research for fiscal year 2012. The National Institute on Aging (NIA)
funded over $335 million in Alzheimer's disease research--approximately
one third of the Institute's research budget. For the fiscal year 2014
President's budget, NIH estimates it will spend a total of $562 million
on research related to this disease.
Alzheimer's research continues to be of tremendous importance to
the NIH and the NIA. The number of individuals with Alzheimer's disease
continues to increase, and our efforts to identify an intervention that
will prevent or treat the disease have borne disappointing results.
However, Alzheimer's disease is one of a number of highly compelling
NIH priorities that include research on heart disease, cancer, mental
illness, and diabetes, as well as cross-cutting research that informs
discovery in multiple disease areas. Both NIH and NIA maintain careful,
rigorous, and ongoing planning and priority-setting processes to ensure
an appropriate balance of resources in basic, clinical, and
translational research, with the ultimate goal of safeguarding the
health and well-being of all Americans.
Question. Do you agree that Alzheimer's research deserves funding
that begins to approach the scope of the problem it poses? If you agree
that there is a problem here, please provide specifics on how you
intend to address this vast disparity in funding within the authorities
you have available to you today.
Answer. In this challenging budget climate, we are continuing to
take a number of steps to leverage our resources to the maximum extent
possible. For example:
--We have developed a rigorous and inclusive process for soliciting
expert advice on research priorities, most notably through the
May 2012 Alzheimer's Disease Research Summit, at which
internationally recognized experts in the field met to
formulate an integrated multidisciplinary research agenda that
will accelerate the development of successful therapies for AD
across the disease continuum. Summit participants also
identified the types of resources/infrastructure and new public
private partnerships that will be necessary to successfully
implement this research agenda.
--We have created the International Alzheimer's Disease Research
Portfolio, a unique database of nationally/internationally
funded AD research, which will enable organizations around the
world to coordinate funding strategies and leverage resources
in order to maximize the impact on public health and avoid
duplication of effort and inefficiency.
--We have conducted an in-depth analysis of the NIH Alzheimer's
disease research portfolio and tied specific milestones to the
goals of the National Plan to Address Alzheimer's Disease.
--Where appropriate, we are coordinating efforts with private funders
and advocacy organizations and actively pursuing public-private
and international partnerships.
Question. I have a longstanding interest in and commitment to
improving the health of all Americans. The research activities at NIH
play a critical role in this issue. The National Institute on Minority
Health and Health Disparities (NIMHD) at NIH only has a budget of
approximately $200 million, paling in comparison to other NIH
Institutes and Centers (ICs) like Human Genome Institute with $500
million or the National Cancer Institute at $5 billion. I stand for
elimination of health disparities to be a national priority--and for it
to be funded like one. The NIMHD's budget should be increased to
fulfill this mission.
As you know, the RCMI program within the NIMHD is responsible for
developing and enhancing the research infrastructure of minority
institutions and directly fosters the development of new generations of
minority scientists. I am disappointed to see the nearly $6.5 million
decrease from fiscal year 2012 funds being requested for the Research
Centers in Minority Institutions program.
Can you please tell me the rationale in the decreased funding for
this important program?
Answer. The Research Centers in Minority Institutions (RCMI)
program provides resources for several critical areas of support for
biomedical, clinical, behavioral, and social sciences research.
Infrastructure development creates a foundation for the research
enterprise through renovation/alteration of new research facilities and
the development of specialized research support capabilities such as
biomedical informatics and research design/biostatistics expertise.
Activities under the RCMI program broaden the opportunities to conduct
clinical and translational research through collaborative projects with
an emphasis on improving minority health and reducing health
disparities. In addition, instructive training and mentored research
training experiences for early-stage investigators interested in health
disparities research facilitate career advancement for junior faculty
members.
The RCMI program was transferred to NIMHD in fiscal year 2012 with
the dissolution of the National Center for Research Resources (NCRR).
At the NCRR, the RCMI program was one of the Center's main programs
aimed at addressing minority health and health disparities. Consistent
with its mission, the NIMHD's program portfolio is exclusively focused
on improving minority health and eliminating health disparities.
Integrating the RCMI program into the NIMHD has been a priority for the
Institute over the past year. This integration means taking a strategic
look at the Institute's priorities, plans, and the overall portfolio,
with the goal of balancing our scientific research investments,
particularly since the RCMI program is programmatically similar to
other NIMHD congressionally mandated programs. In so doing, the NIMHD
seeks to ensure that priorities, programs, and resources are
appropriately aligned consistent with its mission, as well as the
mission of the NIH; the changing pace of science and the health
disparities environment; and that duplication in efforts are identified
and reduced; therefore, a reduction in funding for the RCMI program and
other NIMHD programs was proposed for fiscal year 2014. NIMHD is
committed to the goals and objectives of the RCMI program, and to fully
integrating the program into the Institute in a manner that fosters
collaboration and partnership between RCMI and other NIMHD/NIH
programs, and provide opportunities to enhance the program's
contribution to the Institute's mission, as well as the health and
well-being of the Nation.
Question. The National Center for Advancing Translational Sciences
(NCATS) mission includes a commitment to the behavioral sciences but I
am concerned that the Center has not taken sufficient action to bring
basic behavioral and psychological science discovery into new applied
behavioral interventions. A stronger effort is critical to accelerate
the translation of basic behavioral research discoveries into broadly
disseminated new therapeutics and clinical care products and protocols,
particularly in addressing substance abuse, suicide, depression, and
similarly urgent public health issues confronting the Nation
Answer. To bring the benefits of science more quickly into patient
care, NCATS was formed with the mission to catalyze the generation of
innovative methods and technologies that will enhance the development,
testing, and implementation of diagnostics and therapeutics across a
wide range of human diseases and conditions. NCATS' mission includes
strengthening the entire spectrum of translational research--defined
broadly to include the early steps necessary to develop new
therapeutics, devices and diagnostics from basic discoveries, the steps
necessary to establish real world efficacy, and the research needed to
improve the practical implementation and dissemination of improved
approaches to care.
NCATS is committed to translating basic behavioral and
psychological discovery into interventions that have a discernible
impact on human health. These interventions can span the translational
space of development of a therapeutic, preventive, or diagnostic or
addressing the critical areas of implementation, dissemination, or
adherence. New methods and technologies are needed in addressing
behavioral and psychological interventions as well as greater
integration of these approaches in all portions of the translational
spectrum.
Many Clinical and Translational Science Awards are already
supporting investigators working in these areas through their study
design and biostatistical, regulatory, and community engagement
resources, as well as with pilot project funds for innovative
approaches. For example, the National Institute on Drug Abuse (NIDA)
Clinical Trials Network (CTN) provides an enterprise in which NIDA
treatment researchers, and community-based service providers
cooperatively develop, validate, refine, and deliver new treatment
options to patients in Community Treatment Programs (CTPs). The NIDA
CTN utilizes the resources of the CTSA program at many of its sites for
their studies of new interventions for substance abuse and addiction.
______
Questions Submitted by Senator Richard J. Durbin
Question. Congenital heart disease (CHD) is one of the most
prevalent birth defects in the United States and a leading cause of
birth defect-associated infant mortality. Due to medical advancements
more individuals with congenital heart defects are living into
adulthood.
The healthcare reform law included a provision, which I authored,
that authorizes the Centers for Disease Control and Prevention (CDC) to
expand surveillance and track the epidemiology of CHD across the life-
course, with an emphasis on adults. The Consolidated Appropriations Act
of 2012 provided the CDC with $2 million in new funding for enhanced
CHD surveillance.
Premature deaths across the life-span related to CHD are
unacceptable, however recent data suggest that the number of infant
deaths related to CHD is decreasing. Successful interventions in
infancy and childhood are resulting in an aging population of
congenital heart disease survivors. How is the National Institutes of
Health (NIH) systematically responding to this new population of
survivors reaching adolescence, adulthood, and advanced age? How are
you utilizing adult congenital heart disease research experts in these
efforts? How are you supporting adult CHD experts to grow the field? Is
the NIH offering training grants to grow the field? Is the Pediatric
Heart Network inclusive to adult CHD experts? Is your agency formally
engaging adult populations in CHD research?
Answer. The National Heart, Lung, and Blood Institute (NHLBI) is
keenly aware of the medical and research needs of adults with
congenital heart disease and is supporting a number of activities to
meet these needs.
The Pediatric Heart Network (PHN) is following a cohort of
patients, now aged 13-27, who underwent a Fontan procedure, to correct
a CHD, earlier in life. Assessments include family functioning, quality
of life, neurodevelopment, and access to healthcare as children
transition into adulthood.
The Pediatric Cardiac Genomics Consortium (PCGC), whose goal is to
understand the genetic basis of congenital heart disease and the
contributions of genetics to individual patient outcomes, has enrolled
more than 5000 patients with congenital heart disease, 20 percent of
whom are adults.
The Health, Education and Access Research Trial (HEART-ACHD),
conducted with NHLBI support in partnership with the Adult Congenital
Heart Association (ACHA) and the Alliance of Adult Research in
Congenital Cardiology (AARCC), found that more than 40 percent of
adults with congenital heart disease have a gap in cardiac care of over
3 years, usually during the critical ``transition'' time from the
teenage years into the early 20s. The study investigators also found
that these patients responded well to educational interventions,
resulting in improved knowledge about their conditions and also about
research.
The Research Empowerment for Adult Congenital Hearts (REACH)
project, another ACHA-AARCC collaboration, received NHLBI American
Recovery and Reinvestment Act (ARRA) funding to demonstrate the
feasibility of a patient-centered research model for adults with
congenital heart disease and employ electronic health record technology
to create a national infrastructure for research.
NHLBI has been exploring the use of global unique identifiers
(GUIDs) to link information already collected in a number of different
databases on persons with congenital heart disease. PCGC investigators,
in collaboration with colleagues at the National Institute of Mental
Health (NIMH) who developed the GUID software, have begun a pilot to
assign GUIDs to enrolled patients. If successful, GUIDs will be rolled
out to PHN studies and registries that enroll patients with congenital
heart disease such as the Society for Thoracic Surgery Registry.
NHLBI staff responsible for adult and pediatric cardiovascular
disease research meet regularly with adult congenital heart disease
experts and ACHA representatives to advise them about NIH research
opportunities generally, discuss relevant NHLBI activities, and provide
input into specific research proposals from the community.
NHLBI supports several research training and career development
programs that focus on various aspects of congenital heart disease in
adults, including adherence to treatment and medical outcomes. The
Institute recently developed a PHN Scholars award to fund small pilot
studies and encourage young investigators to conduct research in
congenital heart disease. One of the awards, titled ``The Clinical
Significance of Abnormal Spirometry after the Fontan Procedure,'' will
enroll adult participants in the PHN cohort study mentioned above. The
young investigator's primary mentor directs the Boston Adult Congenital
Heart Service.
Question. In May of 2010, the National Cancer Institute (NCI)
reported that the likelihood of being diagnosed with gastric cancer at
age 25-39 years had increased by almost 70 percent since 1977. There
are minimal symptoms of gastric cancer and it is most often diagnosed
at a late stage when curative treatment is impossible. The American
Cancer Society (ACS) estimates 21,600 new cases of gastric cancer will
be diagnosed in 2013 and 10,990 people will die from the disease.
According to the NCI, about 80 percent of people with stomach cancer
are diagnosed with advanced metastatic cancer. At stage 4, the 5-year
survival rate for gastric cancer is four percent.
Please describe what investments are being made by the NCI to
improve biomedical discoveries pertaining to gastric cancer. The Cancer
Genome Atlas (TCGA) provides a rewarding opportunity to enhance our
understanding of gastric cancer through genomic data. What steps is the
NCI taking to ensure TCGA data are utilized for gastric research?
Further, what steps is the NCI taking to assist gastric cancer
researchers in utilizing the TCGA data to translate promising data from
the research bench to patient bedsides?
Answer. Most gastric cancers arise from the gastric epithelium and
are classified as adenocarcinomas. These are divided into two types,
the intestinal type, which develops in the antrum and is usually well-
differentiated, and the diffuse type, which develops in the body of the
stomach, is poorly differentiated, and usually has a poorer prognosis
than the intestinal type. Gastric cancer does not appear to be
hereditary in most patients. However, a few with the diffuse type have
a hereditary form, arising from an inherited mutation in the E cadherin
gene, which encodes a protein that helps the epithelial cells stick
together. Most cases of gastric cancer are attributable to infection
with the bacterium ``Helicobacter pylori (H. pylori)'', and
progressively stronger evidence suggests that early antibiotic
treatment of this common infection in high-risk patients can reduce the
risk of developing this cancer.
The expected frequency of gastric cancer in 2013 actually
represents a substantial decrease compared to 80 years ago. Since 1930,
the incidence and mortality from this cancer have decreased by more
than 80 percent. The rates continued to decline during the first decade
of the 21st century, according to the 2013 Annual Report to the Nation
on the status of cancer, a joint effort of the American Cancer Society,
the Centers for Disease Control and Prevention, and the NCI. The report
also notes that during this decade, the incidence of gastric cancer
decreased about 15 percent for men (who account for about 60percent of
cases) and a little under 10 percent for women, while its mortality
rate decreased even faster, by more than 30 percent for men and more
than 25 percent for women. Nevertheless, gastric cancer remains a
formidable disease, with most advanced cases having a poor prognosis.
The NCI has more than 80 research projects devoted at least in part to
gastric cancer. Several other NIH Institutes, especially the National
Institute of Allergy and Infectious Disease (NIAID) and the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), also
support research in this area, with emphasis on ``H. pylori''.
Gastric cancer is one of the cancers being studied by The Cancer
Genome Atlas (TCGA), which is a joint research effort of the NCI and
the National Human Genome Research Institute. TCGA is expected to have
a major impact on our understanding of the genetic and epigenetic
changes associated with more than 30 cancer types being studied in
unprecedented detail in this initiative. Tumor tissues from
approximately 325 cases have been collected to date and are being
analyzed. Data is expected to be available next year.
In general, TCGA data is being used to refine the diagnosis of
cancer, to define and delineate both the heterogeneity and the common
features of various cancer types, and to elucidate the molecular
pathways that control the malignant behavior of cancer cells, with the
long-term goal of improving the outlook for cancer patients. These data
are available to qualified researchers through public databases
designed to protect patient privacy. The TCGA team provides extensive
support to researchers accessing TCGA data, including step-by-step
protocols for how to apply and locate TCGA data, as well as preliminary
data analysis to those not able to manipulate the raw data. The
availability and broad utilization of the TCGA data are demonstrated by
the number of publications using TCGA data (to date, already close to
400) and the number of grant applications that include TCGA data (to
date, more than 800). TCGA works with investigators and other
components of NCI to help apply findings from TCGA to the development
of new diagnostics and therapeutics.
The era of targeted treatment of gastric cancer, with research
support from the NCI, has begun even before the TCGA data on this
cancer become available. One recurring therapeutically relevant theme
in cancer is that abnormalities in one tumor type may also be found in
other tumor types. In this context, the protein encoded by the ErbB2
gene, which was found initially to be effectively targeted in breast
cancer by a specific monoclonal antibody, trastuzumab, has also been
found to be overexpressed in some gastric cancers; treatment of these
patients with trastuzumab, in conjunction with standard chemotherapy,
can increase their overall survival, which has led to its approval by
the FDA for the treatment of gastric cancer. Encouraging preliminary
results in gastric cancer have also been seen with therapy directed
against other molecular targets, such as epidermal growth factor
receptor (EGFR) and vascular endothelial growth factor (VEGF).
Prevention is another important NCI-supported area. Research on
``H. pylori'' has provided insight into the observed differences in
oncogenicity among different strains of the bacterium. These basic
research findings have clinical implications, as they can identify
those patients most likely to benefit from eradication of their ``H.
pylori'' with antibiotics.
We anticipate that the detailed information from TCGA and other
research from NCI-sponsored grants will bring new information about the
causes of gastric cancer and its pathogenesis, and will identify new
molecular targets, leading to continued progress in our efforts to
fight this cancer.
Question. In fiscal year 2013 alone, sequestration threatens to cut
the NIH's $30.7 billion budget by almost $1.6 billion. This reduction
in funding jeopardizes NIH's ability to invest in biomedical research
and slows the pace of discoveries. Please summarize the impact of
sequestration on NIH's ability to award grants and support the training
and education of scientists. Please describe the impact of
sequestration on biomedical innovation and how the cuts in funding may
impact patients currently enrolled in clinical trials. Are you aware of
reports quantifying the ripple effect sequestration has on biomedical
research, biotechnology industries, and economic development in the
United States?
Answer. Sequestration requires NIH to cut 5 percent or $1.55
billion of its fiscal year 2013 budget. NIH must apply the cut evenly
across all programs, projects, and activities (PPAs), which are
primarily NIH institutes and centers. This means every area of medical
research will be affected. Compared to fiscal year 2012, NIH expects to
issue approximately 700 fewer competitive research project grants and
admit approximately 750 fewer new patients to the NIH Clinical Center.
In addition, NIH will not increase training stipends for National
Research Service Award recipients in fiscal year 2013. While much of
these decreases are due to sequester, NIH funding is always a dynamic
situation with multiple drivers.
The reductions imposed under sequestration have, and will continue
to have a negative impact on biomedical innovation and the training and
education of young scientists. Medical breakthroughs do not happen
overnight. In almost all instances, breakthrough discoveries result
from years of incremental research to understand how disease starts and
progresses. Even after the cause and potential drug target of a disease
is discovered, it takes on average 13 years and $1 billion to develop a
treatment for that target. NIH is aware that its research funding
directly supports hundreds of thousands of American jobs and serves as
a foundation for the medical innovation sector, which employs 1 million
U.S. citizens. Cuts to NIH funding will have an economic impact in
communities throughout the U.S.
For additional details on the impact of sequestration see: http://
www.nih.gov/news/health/jun2013/nih-03.htm
______
Questions Submitted by Senator Jack Reed
Question. The Congressional Budget Justification for the National
Institute of Child Health and Human Development highlights the National
Children's Study as an ``unprecedented opportunity'' to examine factors
that affect child health and development. However, the research
community continues to raise concerns with the major changes to the
design of this landmark study proposed by the National Institutes of
Health (NIH).
The NIH is supposed to have a contract in place with the IOM to
review the Vanguard Study and new proposals by the end of May. Has that
contract been signed?
Answer. The fully executed Task Order for the contract with the
Institute of Medicine (IOM) to review the study design for the National
Children's Study (NCS) Main Study was signed on May 28, 2013. The
period of performance for the contract began June 3, 2013.
Question. What process are you developing in anticipation of the
final report next year in order to incorporate the recommendations from
the IOM into the methodology for carrying out the Main Study?
Answer. All procurements related to data collection for the Main
Study are delayed until after the IOM report is released. The content
of those solicitations will be based on the recommendations of the IOM
panel, and guided by ongoing public discussions with the NCS Federal
Advisory Committee, the Independent Study Monitoring and Oversight
Committee, and the Federal Consortium. These groups will meet within
the month following the projected public posting of the IOM report in
June 2014. The NIH will integrate the IOM recommendations with input
from the advisory committees to construct the NCS Main Study, including
the Study's methodologies and implementation plan. New solicitations
based on the updated design, methodologies, and implementation plan
will be published at least 60 days following the release of the IOM
report.
Question. Presuming the data already collected could be useful,
will researchers have access to the data already collected while the
IOM conducts its study? Could NIH provide grants through other programs
to use the data that the Federal government already spent $1 billion to
collect?
Answer. Qualified researchers, whether or not they are directly
associated with the NCS, already have access to the Study data, and
will throughout the course of the Study. While we anticipate that many
NIH Institutes and Centers may choose to support grants that utilize
NCS data and samples, access to NCS data and samples will not require
such grants.
Question. I understand that NIH is currently engaged in an internal
process to evaluate how it tracks research data on age, gender, race,
and other patient identifiers. What is the timeline for completing this
process?
Answer. In 2010, the NIH Principal Deputy Director convened an
internal task force to evaluate the policies and procedures related to
the inclusion of women, minorities, and children. Among the outcomes of
the task force was the formation of a new Subcommittee on Inclusion
Governance (SIG) in November 2011, co-chaired by Dr. Janine Austin
Clayton, Associate Director for Women's Health, and Dr. Alan
Guttmacher, Director, ``Eunice Kennedy Shriver'' National Institute of
Child Health and Human Development.
With input from the task force, the SIG is taking a comprehensive
look at the NIH policies regarding the inclusion of women, minorities,
children, and other population groups in clinical research and clinical
trials. The SIG has reaffirmed that the primary goal of NIH inclusion
policies is not enumeration, but rather to ensure that the distribution
of participants in clinical research reflects the population(s) needed
to accomplish the scientific goals of the study. Investigators,
reviewers, and NIH staff all have key roles to play in implementing and
monitoring the policies.
Data collection on the basis of sex/gender, race, and ethnicity is
currently being re-engineered to streamline and simplify the processes
and align better with the electronic grant application procedure. We
anticipate the new system will be deployed in mid-late 2014. With
respect to age, the governance committee is examining how information
about age is provided by grant applicants, reviewed during the peer
review process, monitored during the period that the study is carried
out, and captured by internal NIH systems. In addition, the
subcommittee is analyzing the NIH pediatric portfolio to determine
what, if any, modifications may be needed to ensure the inclusion of
women, minorities, and children in NIH clinical research.
Question. The National Institute of Child Health and Human
Development (NICHD) conducts the majority of pediatric research among
all of the Institutes, but a substantial portion of the research
relevant to children occurs in the Institutes across NIH. For research
projects that are not designed specifically for children--but could
possibly be relevant to children--how does NIH work with investigators
to determine the appropriate participation of children?
Answer. While the NICHD does support a plurality of the pediatric
research funded by the NIH, nearly every NIH Institute and Center (IC)
reports annual support for pediatric research. This support comprises
new and continuing investigator-initiated pediatric research projects,
and projects funded under Funding Opportunity Announcements. These
projects are coded using NIH's Research, Condition, and Disease
Categorization process, a computerized tool that allows the NIH to
provide consistent and transparent information to the public, providing
a list for each fiscal year of all NIH-funded projects related to a
specific research category:
http://report.nih.gov/rcdc/. If a given project is sufficiently related
to an area of pediatric research, it will be included in the Pediatric
Research category.
NIH also supports a range of mechanisms to foster pediatric
research training and career development, and an active pediatric
research loan repayment program, which enables qualified health
professionals who commit to conducting pediatric research for at least
2 years to receive a substantial repayment of their educational loans.
These programs signal to the research community the importance of
pediatric research and the commitment of the NIH to fostering this area
of science.
On a more individual basis, the NIH peer review process helps
researchers to refine and clarify the goals of their research
applications or proposals. Reviewers can be helpful in providing
guidance to applicants who wish to conduct clinical research, including
whether their proposed research includes adequate numbers of
individuals from affected populations. Researchers whose projects
receive funding then work with NIH program officials during the entire
course of the grant or contract, reporting on their progress annually
and receiving input from those officials about whether their aims are
being successfully met.
Question. What more could NIH be doing to support investigators in
pediatric enrollment in their research studies and clinical trials?
Answer. NIH is committed to ensuring that children participate in
the full range of NIH research. In fiscal year 2012, NIH pediatric
research funding totaled approximately $3.6 billion, including studies
in pediatric patients conducted in NIH's intramural research program at
the Clinical Center in Bethesda, MD. NIH supports nearly 100
multidisciplinary center and network programs focused on children's
health needs. These include the Autism Centers of Excellence, the Paul
D. Wellstone Muscular Dystrophy Cooperative Research Centers, and the
Children's Oncology Group. NIH's Office of Rare Diseases Research and
several NIH Institutes and Centers fund the Rare Diseases Clinical
Research Network to facilitate collaboration among experts in many
different types of rare diseases. NIH works with the FDA to administer
the Best Pharmaceuticals for Children Act to support and coordinate
pediatric pharmacology research, with the goal of increasing the dosage
and efficacy information available about therapeutics used by children.
The 60 centers that comprise NIH's Clinical and Translational Sciences
Awards include substantial pediatric expertise.
NIH reviews and awards these and other networks and centers
programs on a regular basis, usually at about 5-year intervals,
ensuring that they are productive and continue to produce the best
science. For example, during the coming year, the NIH will post a
funding opportunity announcement seeking applications for sites to
participate in the ongoing Collaborative Pediatric Critical Care
Research Network, which provides the infrastructure to pursue rigorous
clinical trials and other studies in pediatric critical care medicine.
The eight currently funded sites include pediatric expertise in
pulmonology, cardiology, nursing, and other disciplines essential to
children's health.
______
Questions Submitted by Senator Jon Tester
Question. Most of the research programs that receive NIH research
grants are affiliated with an institution of higher education. I
encourage you to support non-University and non-hospital affiliated
research institutions throughout the country, and in particular to
focus on those located in rural America. Academic and non-profit
institutions based in rural States consistently receive less funding
from the NIH. This oversight is compounded when their work is
overlooked by other researchers, regardless of the quality of their
science.
Due to a lack of higher education or medical facility affiliation,
outstanding research institutions in rural areas often struggle to
obtain research support and funding. I am concerned that the bias
towards researchers with affiliations is short-sighted and overlooks
quality research being done by nimble, independent institutes.
In 2012, the NIH received 63,524 research grant applications. How
many of those grant applications were from facilities and researchers
not affiliated with an institution of higher education? How many of the
grants ultimately awarded went to independent small research
institutions?
Answer. In fiscal year 2012, more than 18,500 applications were
submitted by organizations that were not institutions of higher
learning. Approximately 4,600 of these applications were submitted by
nonprofit independent research organizations, and approximately 800 of
the applications submitted by nonprofit independent research
organizations were awarded grants. Independent research organizations
have a success rate that is comparable to those of research hospitals
and institutions of higher learning.
Question. How do the sequestration cuts further impact the ability
of small research institutions' access to grants? What steps is the NIH
taking to mitigate this issue and ensure that smaller institutions can
compete with larger institutions?
Answer. NIH's post-sequestration fiscal policy applies similar
reductions in funding to all organizations regardless of institution
size or type. Investigators from all types of organizations, including
small academic institutions and research organizations, often develop
collaborations with research personnel at large institutions to gain
access to resources that would not otherwise be available to them. NIH
encourages these collaborations and works to ensure access to research
resources and technologies among its grantees through its sharing
policies (http://grants.nih.gov/grants/sharing.htm)
In addition, the Academic Research Enhancement Award (AREA) grant
program supports small-scale research projects in the biomedical and
behavioral sciences conducted by faculty and students at educational
institutions that have not been major recipients of NIH research grant
funds. Eligible institutions are institutions of higher education that
do not receive more than $6 million per year in NIH support in each of
four of the last 7 years. NIH remains committed to the AREA grant
program in the face of budget restrictions.
______
Questions Submitted by Senator Jeanne Shaheen
Question. Diabetes and its complications significantly impacts our
Nation's health and economy. In fact, new estimates show that the
disease costs our Nation $245 billion annually, a 41-percent increase
from 2007. It is the number one cause of end-stage renal disease
(ESRD), which is the largest driver of Medicare costs at $29 billion in
Medicare in 2009.
I understand that tight blood sugar control can cut in half the
incidence of ESRD and could save Medicare over $126 billion in 25
years. Given this personal and economic toll on our Nation, how is
National Institutes of Health (NIH) prioritizing diabetic kidney
disease? What, if any, are some new insights into the prevention and
treatment in the area of kidney disease?
Answer. There is no known way to restore kidney function once it is
lost, but treatment can usually slow or prevent degradation of kidney
function if diabetic kidney disease is detected early. Therefore,
prevention and early detection of kidney disease are important research
priorities. At the NIH, the Institute with the primary responsibility
for supporting research related to diabetes and kidney disease is the
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), and many of the research efforts included below have been
supported by this Institute.
The NIDDK's Diabetes Control and Complications Trial showed that
intensive blood glucose control reduces risk of complications of the
kidneys, eyes, and nerves of people with relatively recent onset type 1
diabetes; the U.K. Prospective Diabetes Trial established that careful
blood glucose control provides similar benefit to people with recent
onset type 2 diabetes. The NIDDK's Diabetes Prevention Program clinical
trial moved that prevention effort one step earlier, even before the
onset of diabetes. It found that people at risk of developing type 2
diabetes can prevent or delay disease onset and improve their blood
sugar through an intensive diet and exercise intervention, or, to a
lesser degree, with the diabetes drug metformin. In cases where people
receiving the lifestyle intervention actually progressed to develop
type 2 diabetes anyway, their diabetes was found to be easier to
control, and to confer a lower risk for complications.
Despite these efforts to proactively and aggressively manage
diabetes, the risk for end-stage renal disease (ESRD) in patients with
chronic kidney disease (CKD) associated with diabetes remains high.
Moreover, among the larger population of people with CKD who have not
progressed to ESRD, cardiovascular disease poses a significant burden.
The NIDDK's Chronic Renal Insufficiency Cohort (CRIC) Study, which
started in 2001, is a prospective observational cohort study of
approximately 4,000 men and women and is the largest cohort study of
CKD yet undertaken. The objectives of the Chronic Renal Insufficiency
Cohort (CRIC) Study are to improve understanding of the relationship
between CKD disease and cardiovascular disease and to examine
traditional and non-traditional risk factors for progression of these
diseases. An emphasis was placed on recruiting participants at high
risk for ESRD, including persons with diabetes (about one-half of the
study participants), African Americans (also about one-half of the
study participants) and Hispanic Americans. Important scientific
findings are emerging from this study. For example, fibroblast growth
factor 23 (FGF-23) is a growth factor that regulates phosphate
metabolism. Elevated FGF-23 was shown to be an independent predictor of
risk for ESRD in patients with relatively well-preserved kidney
function. FGF-23 may turn out to be a useful biomarker to predict risk
of adverse outcomes in patients with CKD. In a separate study,
increased levels of FGF-23 were associated with an indicator of
cardiovascular disease. CRIC Study investigators have also found a
strong association between eye disease and levels of kidney function,
suggesting that eye disease may reflect underlying CKD. In addition,
the increased burden of cardiovascular disease in Hispanic Americans
with CKD has been documented. These and other findings from the CRIC
Study in the coming years are expected to inform clinical trials and
clinical management practices to reduce the burden of ESRD in the U.S.
The NIH is also seeking to improve the translation and
implementation of treatment approaches to kidney disease and diabetes
in a real-world setting. This research seeks to identify factors that
lead to the adoption, maintenance, and sustainability of science-based
interventions at the practice level, where they can have an immediate
impact on patients' lives, such as improving blood pressure control,
improving laboratory measures of metabolic control or nutritional
status, and/or changes in kidney function. Looking forward, the NIH
recently asked the community to identify research objectives that would
improve our understanding of basic kidney function and aid in the
prevention and treatment of impaired kidney function and prevention of
progression to ESRD, welcoming interested parties to submit, discuss,
and prioritize ideas via an interactive Web site. The approaches
identified may aid in the discovery of new therapies, the
identification of regulatory pathways, the generation of animal models
for preclinical work, and the development biomarkers with clinical
utility so that diabetic kidney disease patient outcomes can be
improved.
Question. Over the past few years, I have been concerned that the
level of funding for NIDDK in the President's budget proposals has not
kept pace with the rate of biomedical inflation and the growing
diabetes epidemic, threatening the ability of NIDDK to continue to make
progress on promising diabetes research.
Would you please share the percentage of grants that NIDDK has been
able to fund over the past 2 years and how this will affect grants/
research going forward?
Answer. In fiscal year 2011 and fiscal year 2012, the National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) used 81
and 80 percent of its regular appropriations, respectively, to fund new
and continuing grants supporting the biomedical research enterprise at
sites around the country. This support includes research project
grants, research centers, careers, other types of research support, and
research training awards for individuals and institutions. In those two
fiscal years, the NIDDK sustained a success rate for funding research
project grants--which receive the majority share of grant funding--of
21 and 20 percent, respectively. These data reflect a combined success
rate for funding research project grants supported by the NIDDK's
regular appropriation and the Special Statutory Funding Program for
Type 1 Diabetes Research. The success rate is defined as the percentage
of reviewed grant applications that receive funding, and is calculated
for the fiscal year. In fiscal year 2013, we expect that the success
rate will decline somewhat due to the loss of funds through
sequestration. At the President's budget request level for fiscal year
2014, the NIDDK anticipates a success rate for funding research project
grants of 22 percent. These relatively stable success rates for
research funding are enabling NIDDK to continue to foster progress and
new advances in diabetes.
Question. Would you also please share how the Administration plans
to ensure that there is a strong investment in the NIDDK in fiscal year
2014 that will lead to breakthrough discoveries and ultimately a cure
of diabetes?
Answer. The President's fiscal year 2014 budget request reflects a
strong commitment of the NIDDK to support research tackling diabetes
and its devastating health and economic consequences. For example, the
funds requested for fiscal year 2014 will enable the NIDDK to continue
major diabetes clinical trials, such as a recently launched multicenter
study of the comparative effectiveness of four common drugs used for
treating type 2 diabetes, and a new trial testing vitamin D for type 2
diabetes prevention. The fiscal year 2014 budget request will also
enable NIDDK to pursue emerging opportunities in the study of diabetes
risk genes in minority populations, which could lead to new therapeutic
approaches. These resources will also support NIDDK's plans for
research that can lead us to personalized medicine for diabetes--for
example, the Institute plans to support research to elucidate how an
individual's genetic makeup affects his or her response to anti-
diabetic medications, such as metformin. Under the President's budget
request, the NIDDK will continue to fund translational research in
fiscal year 2014 and support health information dissemination
activities to bring scientific discoveries in diabetes to real-world
medical practice and other community settings. NIDDK plans for fiscal
year 2014 also include advancing research on brown fat--an exciting new
area of study with therapeutic potential--and moving forward with major
studies of gestational diabetes. Moreover, the NIDDK investment in
diabetes research is augmented by the research activities of the many
NIH Institutes, Centers, and Offices with an interest in diabetes and
its complications, which will also continue in fiscal year 2014. All
these efforts will be further enhanced by fiscal year 2014 mandatory
funds from the Special Statutory Funding Program for Type 1 Diabetes
Research, and the NIDDK will convene an expert panel on June 6-7, 2013,
to obtain external scientific and lay input on future research
directions to be pursued with these funds.
Our plans for fiscal year 2014 are contingent upon Congressional
action, but we are hopeful that the fiscal year 2014 investment in
diabetes research, spearheaded by NIDDK, will continue to lead us
toward new discoveries, new therapies, and possibly cures for diabetes.
______
Questions Submitted by Senator Jerry Moran
Question. As a follow-up to my questions at the hearing on the
Brain Research through Advancing Innovative Neurotechnologies (BRAIN)
Initiative, I understand that the National Institutes of Health (NIH)
is currently working on a scientific plan for this program. However, I
remain concerned that we have no details on how much funding would need
to be provided in the coming years. Could you please provide the
subcommittee a 10-year budget estimation, both for the overall mapping
project and NIH's share in particular.
Answer. It will be imperative that cost estimates be strongly
informed by a rigorous scientific planning process. NIH has charged a
high-level advisory group with developing a plan for the NIH BRAIN
Initiative, which is to include timetables, milestones, and cost
estimates. As part of this process, members will consult the scientific
community, patient advocates, and the general public to ensure that
this plan is informed by stakeholder input. Interim recommendations are
expected late this summer and final recommendations are anticipated in
the summer of 2014. This plan will be publicly available and widely
shared with both the public and with BRAIN Initiative partners.
Question. As the lead institution, do you foresee NIH's funding
role being increased in future years?
Answer. It is anticipated that as the BRAIN Initiative gains
momentum, additional funds may be needed to support promising areas of
research. The pace at which NIH's role might grow in future years will
depend on the relative competing priorities and the overall
availability of funds at that time.
Question. Will NIH be expected to be the primary funding agency in
future years?
Answer. At this time, each funding agency is undertaking an
extensive scientific planning process to identify their specific areas
of focus and to define their potential investments in the BRAIN
Initiative. Given that NIH has such a substantial investment in
neuroscience research, it is certain that we will remain a leader in
advancing the goals of the BRAIN Initiative.
Question. Can you specify the role you see each Federal agency
taking in this initiative?
Answer. In general, NIH will develop new tools, training
opportunities, and other resources. The Defense Advanced Research
Projects Agency (DARPA) intends to explore applications--such as a new
generation of information processing systems and restoration
mechanisms--that dramatically improve the way we diagnose and treat
soldiers suffering from post-traumatic stress, brain injury, and memory
loss. The National Science Foundation (NSF) has expressed a commitment
to supporting research that spans physical, biological, social, and
behavioral sciences. Moving forward the agencies will work in close
collaboration to ensure that their efforts are complementary and
leverage the unique missions of each; ultimately catalyzing an
interdisciplinary effort of unprecedented scope.
Question. What role do you expect private research institutions to
play in the project?
Answer. Currently there are four private partners involved in the
BRAIN Initiative: the Allen Institute for Brain Science, the Howard
Hughes Medical Institute, the Salk Institute for Biological Studies,
and the Kavli Foundation. Each partner will support areas of research
in which they are best positioned to advance the overarching goals of
the BRAIN Initiative. The Allen Institute for Brain Science, a
nonprofit biomedical research organization, is a leader in large-scale
data generation, for example, mapping gene expression in mouse, monkey
and human brains and public sharing of data and tools. The Howard
Hughes Medical Institute, the Nation's largest nongovernmental funder
of basic biomedical research, has a focused investment in developing
and disseminating new imaging technologies for use in model organisms.
The Kavli Foundation will encourage the application of nanotechnology
to neuroscience.
Question. Is it your goal to expand the public-private partnership
for this initiative in the future?
Answer. NIH's first goal is to develop a rigorous scientific plan
for the BRAIN Initiative that is sufficiently informed by a broad and
inclusive process. After the scientific plan is established, NIH will
continue to seek ways to leverage public-private partnerships.
Question. What would happen if each of the proposed agencies does
not provide the requested amount in fiscal year 2014?
Answer. The NIH Director recognizes the tremendous opportunity of
the BRAIN Initiative and is committed to ensuring its success. In the
event that funds are not provided for this Initiative, NIH will
continue to support smaller aspects of this project that continue to
advance neuroscience research. However, the scale of this project might
be minimized in comparison to the President's bold vision of truly
``revolutionizing'' our understanding of the human brain.
Question. The goal of the Institutional Development Award (IDeA) is
to broaden the geographic distribution of NIH funding for biomedical
and behavioral research. This is the second year in a row that NIH has
proposed reducing funding for the IDeA program after Congress restored
funding in the prior year. I question why the budget would reduce
funding for the IDeA program whose purpose is to diversify biomedical
research to all regions of the country when the budget requests new
funding for new proposals to diversify the biomedical workforce. Why is
NIH not supporting level funding for the IDeA program which is already
a critical component of diversifying the biomedical research capacity?
Answer. At a time of difficult economic environment when many
investigators throughout the Nation are struggling to compete for NIH
funding, the allocation of funding for selected States to increase
their competitiveness must be balanced with other NIH initiatives for
promoting a more diverse biomedical workforce nationwide.
Question. The IDeA program is operating under a budget of $262.5
million for the remainder of fiscal year 2013. Dr. Collins, if your
budget request of $226 million were agreed to, the IDeA program would
issue no new Centers of Biomedical Research Excellence (COBRE) awards
in fiscal year 2014 and cut the COBRE grants currently funded. Why
would you propose funding reductions that require reducing existing
awards to a current program whose goal is to increase diversity, while
then proposing a new diversity initiative within the Common Fund?
Answer. The IDeA Program is a funding set-aside designed to build
research capacity in selected States to the point where investigators
in these States can compete for NIH funding. We have proposed returning
the IDeA program appropriation to the level where it had been before
the one-time spike in fiscal year 2012. The IDeA program is a
congressionally mandated program envisioned as a long-term initiative
for building biomedical research competitiveness of selected States
while the Common Fund initiative is a limited term program designed to
support student development from underrepresented groups.
Question. Given today's Federal budget constraints and drug
companies' hesitation to pursue costly development of drugs that may
have a low success rate, I believe programs like NCATS' Learning
Collaborative is an innovative model to help address these issues. As
we discussed in this hearing last year, the University of Kansas Cancer
Center has engaged in a partnership with the National Center for
Advancing Translational Sciences (NCATS) and the Leukemia & Lymphoma
Society to repurpose auranofin, an arthritis drug, for use on a rare
form of blood cancer. The Learning Collaborative has repurposed a drug
from the shelf into a clinical trial in less than 2 years, and at one-
sixth the cost of developing a new drug. Dr. Collins, could you talk
about the progress the Learning Collaborative has made?
The success of this project appears clear--within 2 years, The
Learning Collaborative has moved a compound to treat arthritis into a
Phase IIa Clinical Trial to treat Chronic Lymphocytic Leukemia (CLL), a
rare blood cancer. This project has not only shown promising results
for those suffering from CLL, but the research studying auranofin has
also helped broaden our understanding of how the drug may work to fight
other forms of cancer. As a result of this initiative, the University
of Kansas was able to submit two additional investigational new drug
applications to study auranofin's effects on other forms of cancer. Dr.
Collins, do you expect this model to be replicated with other
repurposing initiatives?
Answer. Parallel, independent studies conducted at The University
of Kansas (KU) and University of Rochester demonstrated positive
results when using auranofin to treat a rare, difficult to treat
lymphoma called Mantle Cell Lymphoma. Investigators at both NCI cancer
centers believe that auranofin acts synergistically with a class of
anticancer agents called proteosome inhibitors (e.g., Velcade or
bortezomib) to treat this cancer. Velcade is not very effective when
given alone to treat this lymphoma. In a series of collaborative
experiments with University of Kansas, NCATS obtained results
supporting the use of Velcade with auranofin to treat this cancer. As a
result, on March 15, 2013, KU investigators filed a second
Investigational New Drug (IND) application with the Food and Drug
Administration (FDA). In late April, FDA cleared researchers to proceed
with a clinical proof-of-concept trial, studying auranofin alone and in
combination with Velcade, in lymphoma patients. This trial will be
conducted at the University of Rochester, University of Iowa, and
University of Kansas NCI cancer centers.
Investigators at KU submitted a third IND on March 28, 2013,
seeking clearance to study auranofin for the treatment of
gastrointestinal stromal tumors (GIST). The cancer, GIST, afflicts
approximately 4,000 U.S. patients. Auranofin is active, in the test
tube, in treating GIST that is both sensitive and resistant to Gleevec.
Very recently, investigators received clearance from the Food and Drug
Administration (FDA) to proceed with this trial. The trial will be
conducted at the University of Kansas Cancer Center and Children's
Mercy Hospital in Kansas City, MO.
Auranofin was discovered as active against these cancer cells in
screens of the NCATS Pharmaceutical Collection (NPC), a comprehensive
collection and database of approved and investigational drugs. NCATS
collaborates with investigators worldwide to identify other drugs in
the NPC that can be repurposed for unmet medical needs.
Question. How will NCATS share the lessons learned in these types
of collaborations so others in the field of translational research can
benefit?
Answer. Sharing the lessons learned is the best way for NCATS to
increase the impact of its programs. When the Center develops a
strategy and demonstrates the value of that strategy, the dissemination
and adoption of the strategy by other organizations in both the public
and private sectors is how NCATS will amplify the impact of its
investment. Such dissemination is accomplished via sharing of data and
template agreements in public Web sites, peer-reviewed publications,
and presentations to stakeholders. NCATS uses all of these strategies
to disseminate lessons learned and communicate the value of our
strategies. For example, NCATS collaborated with FasterCures, a center
of the Milken Institute, to disseminate the collaborative lessons from
The Learning Collaborative with KU and the Leukemia & Lymphoma Society
(LLS) via webinars, and made the Research Collaboration
Agreement (http://train.fastercures.org/pdf/tools/
CollaborationAgreementNCATS
012412.pdf) and Memorandum of Understanding (http://
train.fastercures.org/pdf/tools/RedactedMOU5June2012.pdf) public for
others to use.
Question. Through Federal investment, the NIH has advanced our
understanding of health for the last century. But the NIH provides more
than medical discoveries, it creates and sustains jobs and produces
measurable benefits to the American economy. Dr. Collins, at a time
when global competitiveness in biomedical research is intensifying, and
our global competitors are spending more funding to advance their own
biomedical research efforts, can you discuss the ramifications of
reducing the Federal investment in NIH?
Answer. Reducing the Federal investment in medical research has
many ramifications. NIH is currently the largest funder of biomedical
research in the world, and the work it supports and conducts leads to
advances in the diagnosis, treatment, and prevention of disease. As you
note, NIH research also has significant economic benefits and creates
and sustains jobs in research and development. In ``NIH's Role in
Sustaining the U.S. Economy'', United for Medical Research, an advocacy
organization, calculated that the $23.7 billion spent by NIH
extramurally in the U.S. in 2011 directly and indirectly supported
432,094 jobs. NIH funding also affects the size of the bioscience
industry, according to the Milken Institute's 2012 report, ``Estimating
Long-Term Economic Returns of NIH Funding on Output in the
Biosciences''. The authors, representing an advocacy organization,
argue that a $1 increase in NIH funding will increase the size (output)
of the bioscience industry by at least $1.70 in that year.
NIH's current operating budget, post sequestration, of $29.15
billion is about 5 percent below last year's budget. In addition, in
inflation-adjusted terms, the NIH budget has declined almost every year
since 2003. Other countries are increasing their investment and
threatening the U.S.'s leadership in the global life sciences industry.
Between 1999 and 2009, Asia's share (including China, India, Japan,
Malaysia, Singapore, South Korea, Taiwan, and Thailand) of worldwide
R&D expenditures grew from 24 percent to 32 percent, while U.S. R&D
expenditures declined from 38 percent to 31 percent. In addition, the
European Commission has recently urged its member nations to increase
substantially their investment in research, recommending budgets of 80
billion euros ($108 billion) in 2014-2020, a 40-percent increase over
the previous seven year period.
As other countries continue to devote a larger share of their
annual budgets to R&D, it will be essential for the U.S. to continue to
invest in biomedical research, training, and infrastructure. These
investments--critical components in the ``engine of innovation''--will
be needed to keep the U.S. in the position of worldwide leader. A
sustained commitment to biomedical research, will allow NIH to keep up
the pace of advancements in the treatment, diagnosis, and prevention of
disease and in the improvement of the public health and for the U.S. to
maintain its global lead in biomedical innovation.
Question. Dr. Collins, diseases such as Alzheimer's, cancer,
diabetes, and heart disease affect millions of Americans and cost
hundreds of billions of dollars to treat each year. We all know people
who have been impacted by each of these diseases and how important the
development of preventive measures, diagnostic tools, and new
treatments are. Yet recent estimates for this year project that the NIH
will fund the fewest number of new and competing research projects
since 1998--the first year of the doubling of the NIH. What steps are
being taken to ensure that we continue to make progress against these
and other diseases?
Answer. NIH is operating at a program level of $29.15 billion in
fiscal year 2013, a decrease of about 5 percent from fiscal year 2012.
Despite this reduction, NIH remains committed to funding outstanding
science and will continue to strive to find new, more effective ways to
prevent, treat, and cure human diseases. NIH also remains committed to
supporting the other critical elements of our mission, namely training
and development of talented researchers and maintaining a
technologically advanced scientific infrastructure.
The sequester is having real effects on our ability to support both
new and competing research projects as well as non-competing
continuation awards. Although NIH is likely to make fewer competing
awards in fiscal year 2013, we will be trying to keep the average size
of competing awards constant at fiscal year 2012 levels. Most non-
competing continuation awards that have already been made in fiscal
year 2013 were funded up to 10 percent less than the previously
committed level. Although we may be able to make some adjustments
during the year depending on the final level of each NIH Institutes and
Centers' (ICs) appropriation, we will not be able to restore them to
the previous level. Finally, new research infrastructure and core
facilities are now ready for use, but without support for researchers
who can take advantage of these resources, their productivity will not
be fully realized.
NIH will be strategic in deploying its resources in fiscal year
2013 to achieve continued success in addressing the public health
challenges of today and tomorrow including those you reference in your
question. For example, to advance the progress of research on
Alzheimer's disease, NIH will enable rapid sharing of data, disease
models, and biological specimens, and it will promote the building of
new multidisciplinary translational teams and create both physical and
virtual sites where these teams can operate. NIH will also establish
new public-private partnerships to speed drug development by
repurposing abandoned compounds. NIH's Cancer Genome Atlas (TCGA), a
joint effort of the National Cancer Institute (NCI) and the National
Human Genome Research Institute (NHGRI), is a publicly accessible
database that is opening new avenues for the identification of useful
biomarkers and the development of targeted therapies. Among efforts in
diabetes research, NIH will work to translate the important findings of
controlled clinical trials for diabetes prevention or treatment into
approaches that are effective, affordable, safe, and sustainable in
real world settings. For heart disease, NIH is funding studies of the
cellular and molecular mechanisms underlying large conduit-artery
stiffening in hypertension and the examination of the temporal
relationship between arterial stiffening and the development of
hypertension in animal models.
Using a priority setting process that strikes a dynamic balance
between multiple factors, including ongoing and newly emerging public
health needs, scientific opportunities, responses to unexpected
scientific findings, and the need to sustain longer-range workforce and
infrastructure development, NIH is able to support all of our mission
areas. This process and the continuous monitoring and evaluation of
research portfolios help ensure an ever-increasing understanding of
basic biological functioning and the application of that understanding
to the amelioration of disease burden. Nevertheless, decreased funding
will limit NIH's ability to fund all of the most promising scientific
ideas and affect the pace of the advances we generate in the treatment,
diagnosis, and prevention of disease and in the improvement of the
public health.
Question. The fiscal year 2014 budget request proposes a multi-
agency reorganization of science, technology, engineering, and
mathematics (STEM) education, which includes nine consolidations of
NIH-related STEM programs to other agencies. What is NIH's plan with
respect to the STEM education proposal?
Answer. The fiscal year 2014 President's budget proposes to
consolidate a number of science education programs under the Department
of Education, the National Science Foundation, and the Smithsonian
Institution. NIH staff have participated in preliminary transition
planning discussions with representatives in those three agencies, and
we are preparing for phase out of those programs. While K-12 science
education is important, it is not a core NIH function given our focus
on training the scientific workforce at the undergraduate, graduate,
and doctoral levels.
Question. NCATS' Learning Collaborative has incorporated resources
from the NIH, a State university, and a nonprofit advocacy organization
to develop new therapeutics for blood cancers. It is my understanding
that this public-private collaboration was made easier by using a
Collaboration Research and Development Agreement (CRADA). Do you expect
NCATS to continue to use CRADAs in future collaborations?
Answer. A Collaboration Research and Development Agreement (CRADA)
is a useful tool for formalizing collaborations between intramural NIH
scientists and university and industry scientists, and NCATS is
utilizing this agreement type for many of its collaborations with for-
profit and non-profit organizations. NCATS anticipates continued usage
of the CRADA mechanism, due to the collaborative nature of many of
NCATS programs.
Question. Do any changes need to be made to allow for the NIH to
better leverage the benefits of CRADAs?
Answer. While there are various mechanisms that support
collaborations between companies and NIH intramural scientists, the
CRADA is the only mechanism that permits the NIH to offer an upfront
option to companies to license inventions that may be made within the
scope of the collaboration agreement, and it also permits the
collaborating company to provide funds to the NIH in support of the
research. Over the last few years, the number of CRADA collaborations
has steadily increased with new inventions being developed as a result
of these critical scientific relationships. Currently, NIH is
developing an online system that will tailor the CRADA terms to the
specific needs of the collaboration and streamline the negotiation and
implementation processes. As NCATS and other ICs explore innovative
collaborative relationships with the private sector, NIH is flexible in
adapting CRADAs to meet those programmatic needs.
______
Questions Submitted by Senator Richard C. Shelby
Question. The budget proposes a government-wide realignment of
Federal science, technology, engineering, and mathematics (STEM)
education programs. Dr. Collins, do you support the Office of
Management and Budget's proposal to move nine of the National
Institutes of Health's (NIH) STEM education programs to other agencies?
Answer. The NIH supports the proposal in the fiscal year 2014
President's budget to consolidate K-12 science education programs under
the Department of Education, the National Science Foundation, and the
Smithsonian Institutions. NIH staff are participating in initial
transition planning discussions with representatives in those three
agencies, and we are considering phase out of those programs. While K-
12 science education is important, it is not a core NIH function given
our focus on training the scientific workforce at the graduate and
doctoral levels.
Question. Without Congressional approval, NIH could still move
forward to consolidate STEM education programs within NIH. Do you think
you will move in that direction should Congress not act on the
government-wide realignment?
Answer. The NIH is supportive of efforts to improve coordination of
Federal science education programs consistent with the President's
desire to take action to improve student outcomes. The NIH is reviewing
its K-12 science education programs in light of reorganization and
consolidation of STEM education proposed in the fiscal year 2014
President's budget, but cannot speculate on a scenario where Congress
does not act on the government-wide proposal.
Question. Dr. Collins, the budget request proposes a new diversity
program in the Common Fund called NIH Building Infrastructure Leading
to Diversity (BUILD). The budget justification states that the program
would support initiatives to strengthen the infrastructure of
``comparatively under-resourced institutions.''
What are the eligibility criteria for this proposal?
Answer. NIH intends for BUILD awards to involve partnerships from
multiple types of institutions, but only those that are referred to as
Primary Institutions would submit applications. Primary Institutions,
the applicant organization, are intended to be those that have the
primary responsibility for implementation of the project and for
management of the award. NIH intends for Primary Institutions to be
baccalaureate-granting colleges/universities that receive less than
$7.5 million (total costs) in NIH research project grants (RPG)
(average of fiscal years 2010-2012) and have a pool of undergraduate
students, at least 25 percent of whom are supported by Pell grants. The
BUILD Primary Institution eligibility criteria are intended to target
funds to relatively under-resourced institutions (less than $7.5
million in NIH RPG funding) with a demonstrated commitment to students
from diverse backgrounds that have been historically underrepresented
in the biomedical research workforce. The intended requirement that
BUILD institutions have a substantial pool of students from
disadvantaged backgrounds (at least 25 percent must be Pell grant
recipients) is based on the recognition that (1) many students from
economically disadvantaged backgrounds are underrepresented in the NIH
workforce in the fields of biomedical, behavioral, and clinical
research, and (2) institutional commitment to these students often
comes at the expense of investments in research infrastructure.
Primary Institutions will be encouraged, but not required, to
develop appropriate partnerships in order to optimally position
themselves to provide a rigorous environment for research training.
Partnerships involving a Primary Institution and one or more of the
following institution types are encouraged:
Pipeline Partner Institutions are intended to be 2- or 4-year
undergraduate institutions with students that will enrich and expand
the pool of students eligible for BUILD scholarships. Research Partner
Institutions are intended to be research intensive institutions with
committed investigators able to serve as effective research mentors for
BUILD scholars. Research partnerships are intended to expand education
and research opportunities available to BUILD scholars, work with
Primary Institutions to develop innovative curricula, and provide
sabbatical opportunities to faculty from Primary Institutions. Academic
institutions, government institutions, industry, and nonprofit research
institutions may all be considered as potential Research Partners.
Graduate/Medical Partner Institutions are intended to be medical,
dental, or graduate research institutions with no undergraduate program
but with a pool of doctoral-level students engaged in research and/or
planning a research career, and less than $7.5 million (total costs)
through research project grants (average of fiscal years 2010-2012).
Primary Institutions and Graduate/Medical Partner Institutions are
intended to work collaboratively to provide joint programs for both
undergraduate and graduate students.
In addition to the BUILD initiative, the NIH Common Fund's
``Increasing the Diversity of the NIH-Funded Workforce'' program
includes two other initiatives: the National Research Mentoring Network
(NRMN) and the Coordination and Evaluation Center (CEC). The NRMN is
intended to facilitate the development of robust mentoring
relationships by coordinating nationwide pairings of scientific leaders
and early career scientists (undergraduate students through junior
faculty members) who may benefit from additional mentoring, including
but not limited to individuals from underrepresented backgrounds. The
CEC is intended to serve as a centralized hub to enable the integration
of BUILD and NRMN with existing programs, assessing the impact of the
BUILD and NRMN initiatives from the earliest stages of implementation
to provide early indications whether the novel approaches implemented
by BUILD and NRMN awardees are having a meaningful effect. NIH intends
for both the NRMN and CEC to be open to any institution within the
United States, including academic institutions, nonprofits, and
professional organizations.
Question. How many institutions do you propose funding with fiscal
year 2014 funds?
Answer. In fiscal year 2014, we expect to support approximately ten
Primary Institutions within BUILD, each of which will be encouraged to
form partnerships with other institutions as appropriate. In addition,
we expect to support one institution within NRMN, and one institution
within CEC. The number of institutions supported will be contingent
upon availability of funds and receipt of a sufficient number of
meritorious applications.
Question. How much do you expect the awards to be?
Answer. Details of the anticipated budgets for BUILD, NRMN, and CEC
will be provided in the Funding Opportunity Announcements for these
initiatives, which are expected to be released in the fall of 2013. As
described in a presentation to the NIH Advisory Committee to the
Director (http://acd.od.nih.gov/Diversity-in-the-
Biomedical-Workforce-Implementation-Plan.pdf), the entire ``Increasing
Diversity of the NIH-Funded Workforce Program'' budget is planned to
average approximately $50 million per year. The majority of these funds
are intended to go towards the BUILD initiative.
All anticipated award budgets are contingent upon the availability
of funds and the receipt of a sufficient number of meritorious
applications.
Question. Could you please provide additional details beyond those
provided in the Funding Opportunity Announcement, related to the
expected collaboration between the Primary, Pipeline, Research and
Graduate/Medical Partner institutions? (OD/Common Fund)
Answer. NIH intends for BUILD Primary Institutions to be
encouraged, but not required, to partner with Pipeline Partners,
Research Partners, and/or Graduate/Medical Partner Institutions. The
intent of encouraging these partnerships is to provide the best
research training environment for students involved in the BUILD
program. Partnerships with Research Partners would allow students from
under-resourced institutions to participate in robust research
experiences that are unavailable at their home institutions.
Participation in mentored research experiences is a critical factor in
determining whether undergraduate students choose to pursue a research
career; therefore, engaging students from underrepresented backgrounds
in meaningful research experiences is anticipated to have a major
impact on the diversity of the biomedical research workforce. Primary
Institutions and Research Partners are intended to also work together
to develop novel curricula, and faculty from Primary Institutions are
intended to have the opportunity to pursue sabbatical activities at
Research Partner Institutions. Partnering with Pipeline Partner
Institutions will enrich the pool of students eligible to participate
in the BUILD programs, so that students at 2- or 4-year colleges (such
as community colleges) can benefit from research training experiences
not available at their home institutions. Similarly, partnerships with
Graduate/Medical Partner Institutions are intended to also expand the
pool of BUILD-eligible scholars by providing additional research
experiences to doctoral-level students at these institutions. NIH
intends for Graduate/Medical Partner Institutions to include
Historically Black Medical/Graduate Schools, which have a rich history
of training students from underrepresented backgrounds and have a
robust pool of students who may benefit from BUILD activities.
Question. Dr. Collins, you stated at the hearing that while the
Administration has proposed an overall goal of mapping the human brain,
there are no specific scientific details or timeline you can put
forward at this time. While I understand that you expect fiscal year
2014 to be a scientific planning year, it is critical that the
Appropriations Committee has a full understanding of the goals and
timeframe of this project before funding is appropriated. Therefore,
can you please provide the subcommittee with the following information:
The BRAIN Initiative has no clearly defined goals or endpoint. When
do you expect to have a scientific framework in place to answer these
critical questions?
Answer. NIH is undertaking a rigorous scientific planning process
to determine the scientific aims of the NIH component of the Brain
Research Through Advancing Innovative Neurotechnologies (BRAIN)
Initiative, which is anticipated to include a plan for timetables and
milestones. As part of this process, members will consult the
scientific community, patient advocates, and the general public to
ensure that this plan is informed by a broad and inclusive input. Final
recommendations are anticipated in the summer of 2014, at which time
the NIH will be able to comment on the scientific framework.
Question. How long do you estimate mapping the human brain will
take?
Answer. The goal of the BRAIN Initiative is not actually to map the
brain, per se, but rather to accelerate the development and application
of new technologies that will enable researchers to produce dynamic
pictures of the brain that show how individual brain cells and complex
neural circuits interact at the speed of thought. These technologies
will open new doors to explore how the brain records, processes, uses,
stores, and retrieves vast quantities of information, and shed light on
the complex links between brain function and behavior. The group
advising the NIH on the scientific framework for the BRAIN Initiative
has been asked to articulate the short, mid, and long term objectives
required for achieving these aims.
Question. What goals do you expect to accomplish in 1, 3, and 5
years?
Answer. It is premature to speculate on the accomplishments in the
absence of a strategic plan outlining the scientific goals of the
Initiative.
Question. Do you expect the Department of Defense and the National
Science Foundation to continue to financially support this project for
the duration?
Answer. NIH cannot comment on the financial commitments of the
other agencies. However, given the different perspectives and strengths
of each agency, NIH sees much benefit in having other agencies
involved.
Question. What specific role will each Federal agency contribute to
this project?
Answer. In general, NIH will develop new tools, training
opportunities, and other resources. The Defense Advanced Research
Projects Agency (DARPA) intends to explore applications--such as a new
generation of information processing systems and restoration
mechanisms--that dramatically improve the way we diagnose and treat
soldiers suffering from post-traumatic stress, brain injury, and memory
loss. The National Science Foundation (NSF) has expressed a commitment
to supporting research that spans physical, biological, social, and
behavioral sciences. Moving forward the agencies will work in close
collaboration to ensure that their efforts are complementary and
leverage the unique missions of each; ultimately catalyzing an
interdisciplinary effort of unprecedented scope.
Question. It has been reported that the first several years of the
program will emphasize the development of technologies. However, this
approach has been criticized and some neuroscientists have said that
money would be better spent by first figuring out what needs to be
measured and then determining the best means to measure them. How do
you respond to this critique?
Answer. The group advising the NIH on the scientific framework for
the BRAIN Initiative has been asked to review the neuroscience
landscape in order to determine the opportunities, challenges, and
impediments in neuroscience research. It is precisely through this
analysis that they will indeed assess what needs to be measured or what
is missing in order to focus the investment in promising areas of
research.
Question. The European Union (EU) has a similar initiative called
the Human Brain Project. How is the BRAIN Initiative different than the
EU program?
Answer. The EU's Human Brain Project and the BRAIN Initiative share
the broad goal of advancing the understanding of the brain and its
diseases. They also both recognize that technological opportunities are
emerging to accelerate progress toward that goal. However, the two
initiatives differ in their emphasis. The European Project emphasizes
the development of informatics and computer infrastructure to
systematically integrate all available data into unifying models of the
brain. The BRAIN Initiative will focus on the development of tools that
will transform our ability to gather new data, heretofore impossible to
acquire, that will advance understanding of how millions of brain cells
work together in circuits that enable us to think, act, and sense the
world. That said, it is important to emphasize that the EU Project is
new, multi-faceted, and will develop over time, and the BRAIN
Initiative is in its early formative stages. As the BRAIN Initiative
Working Group develops plans for the BRAIN Initiative, including how to
analyze and disseminate the data it generates, the group is building
bridges to the EU Project and to other projects outside of the U.S.
government to take advantage of all possible opportunities for synergy.
Question. Do you expect collaboration with the EU on the ultimate
goal of mapping the brain in its entirety?
Answer. As part of the working group's charge, they have been asked
to identify areas in which collaboration with others (i.e. foundations,
industry, other agencies) would result in either complementary
activities or the leveraging of efforts. EU efforts will be considered
in this analysis.
______
Questions Submitted by Senator Lamar Alexander
Question. You testified that sequestration caused the National
Institutes of Health (NIH) to cut 700 extramural grants. Was intramural
grant funding similarly affected? If so, are extramural and intramural
on the same ``playing field?'' It is my understanding that extramural
grants must go through a competitive peer-review process, which might
not be the case for intramural grants.
Answer. The NIH Intramural Research Program has been subjected to
similar cuts due to sequestration as extramural grants. The cuts in
intramural and extramural research similarly affect hiring, purchase of
equipment and supplies, scientific travel, etc. In addition, some
clinical trials conducted through extramural research are being
delayed, and reductions in intramural research will cause approximately
750 fewer new patients to be admitted to study protocols at the NIH
Clinical Center. All NIH intramural principal investigators undergo
rigorous peer review at least once every 4 years by outside scientific
experts whose advice affects the resources allocated to them. These
experts are members of the scientific community who receive extramural
grants, and they are thus in a position to compare the intramural
research with research that is funded by extramural grants. Intramural
scientists do not, however, receive actual grants but rather compete
for and receive internal funding and resources for scientific programs
and projects, thus making direct comparisons in numbers of grants
difficult.
Question. According to your testimony, an average of 15-16 percent
of grant applications to NIH submitted actually receive funding.
Are all grant applications submitted included as part of this
statistic or do are only those grants that pass a minimal standard
initial screening process included?
Answer. The National Institutes of Health (NIH) reports success
rate statistics http://report.nih.gov/NIHDatabook/Charts/
Default.aspx?showm=Y&chartId=124&cat
Id=13 on the RePORT Web sites for various grant application types. The
success rate in fiscal year 2012 for research project grants was 18
percent, and it is projected that the success rate for fiscal year 2013
will decline. Decreases in the Success rates are tied to availability
of funding and the number of applications received, thus the overall
growth in the number of applications reduces the success rate.
The success rate describes the percentage of grant applications
accepted for peer-review that were subsequently funded. A small
fraction of applications submitted to NIH are not accepted for review
for various reasons, and thus, are not included in the success rate
calculation. Examples would include if the applicant institution is
ineligible for the funding program for which it has applied, or does
not have active registrations in the United States System for Award
Management and/or NIH's Electronic Research Administration (eRA)
Commons. Some applications are not accepted because they are missing
required information or violate application formatting requirements.
Finally, a small number of applications are submitted that describe
research projects that are virtually identical to applications
previously reviewed, or do not fall within NIH's mission, and are not
accepted for review.
Question. Of the total number of grant application submitted, what
percentage are such that, even with unlimited funding, would not be
worthy of funding? For what reasons would they be excluded?
Answer. Most grant applications submitted to the NIH are from
recognized scientific experts and many are worthy of funding.
Nevertheless, it is desirable to maintain a highly competitive process
to identify the best science to support with the resources available.
As part of the initial peer review process, reviewers have the ability
to identify a particular application as Not Recommended for Further
Consideration, if it lacks significant and substantial merit; presents
serious ethical problems in the protection of human subjects from
research risks; or presents serious ethical problems in the use of
vertebrate animals, biohazards, and/or select agents. Applications
designated as NRFC do not proceed to the second level of peer review
(National Advisory Council/Board) because they cannot be funded. This
is a very rare event, and all other applications are considered to have
been recommended by the initial review group as eligible for funding.
The Institutes and Centers typically regard applications that have been
assigned Overall Impact Scores better than the 33 percentile to be
worthy of consideration for funding. However, each NIH Institute and
Center (IC) may fund applications that do not meet this threshold, if
they can establish high program relevance. Indeed, the success rate for
Research Project grants reached 32 percent during 1999 to 2001;
however, the high success rate is tied to the relatively low number of
applications received. For example, in 1999, NIH received about 26,000
applications, compared to the over 50,000 received in 2012.
Question. How is NIH working with private foundations regarding
young investigator awards? What percent of young investigator awards
are being funded by NIH?
Answer. NIH identifies New Investigators as those who have not
previously competed successfully as the Project Director or Principal
Investigator for a substantial NIH independent research award, e.g., an
investigator-initiated R01 Equivalent Grant (R01, DP2 or R37). It is
the goal of NIH to support New Investigators on new, R01 equivalent
awards at success rates comparable to those of established
investigators submitting new or Type 1 applications. In fiscal year
2012, NIH awarded 1,286 competing R01 equivalent grants to New
Investigators, for a success rate of 13 percent. There were 2,429
comparable awards made to established investigators, for a success rate
of 15 percent.
NIH has a novel program for intramural scientists that is
coordinated collaboratively with the Lasker Foundation. The Lasker
Clinical Research Scholars Program supports a small number of
exceptional clinical researchers in the early stages of their careers
to promote their development as independent investigators. Scholars
receive 5 to 7 years of support as an independent principal
investigator in the NIH Intramural Research Program, followed by the
competitive opportunity for additional years of financial support,
either at the NIH or at an extramural research institution.
Question. The National Cancer Institute (NCI) assembled a list of
24 questions that should engage scientific community in debate and
further advancements in cancer research. What is the timeline for
measurable outcomes for the NCI Provocative Questions program?
Answer. The Provocative Questions Initiative (PQI) has lofty goals
but it is less than 2 years old, so the outcomes that can be measured
now are largely procedural and subjective. The PQI was designed to
engage the scientific community in efforts to identify important and
often long-standing questions in cancer research--e.g., how obesity
contributes to the development of cancers or why some cancers respond
to specific drugs when others do not--and to address them
experimentally, using new methods and new information. Part of the
motivation was to encourage the research community to take risks and
address important problems, even in this time of limited funding and
low success rates. The ultimately desired outcomes of the PQI will be
answers to at least some of the questions and applications of the
answers to the ways in which cancers are prevented, diagnosed, and
treated. But such outcomes cannot be expected for at least 5 to 10
years.
Other aspects of the PQI--its attractions for the cancer research
community and its capacity to generate interest and exciting ideas--can
be measured, however, even at this early stage. For instance, the PQI
was designed to stir imaginative, inter-disciplinary thinking by asking
working scientists, rather than NCI program directors, to develop the
Provocative Questions. As measures of the enthusiasm generated by this
project, we have kept track of the many PQI workshops that the NCI has
conducted throughout the country, bringing scientists from different
disciplines together to propose and discuss questions; and we have
observed the heavy traffic on our PQI Web site, where questions are
posted and debated. When we selected twenty-four questions to be
addressed in the first round of competition for grants, we received
over 750 applications, indicating a high level of interest and we
funded slightly more than fifty of the best applications. The NCI is
currently evaluating a second set of applications received in response
to Provocative Questions.
Question. Please address any overlap between the NIH Common Fund
and the NIH National Center for Advancing Translational Sciences. How
are these two areas coordinating efforts?
Answer. By design, the Common Fund is not separate from the ICs.
Scientific oversight for each Common Fund Program is provided by two or
three IC Directors who serve as co-chairs. Requests for applications
(RFAs) are issued from the IC of one of the co-chairs and day-to-day
and long-term program oversight is provided by staff from the co-
chairs' ICs. In addition, each program has a trans-IC Working Group
composed of program staff from as many ICs as are interested in
participating. Successful coordination of this distributed management
model is the responsibility of the Office of Strategic Coordination in
the Division of Program Coordination, Planning, and Strategic
Initiatives (DPCPSI), NIH Office of the Director (OD). There are
several programs within the National Center for Advancing Translational
Sciences (NCATS) that originated from, and are currently being funded,
either fully or partially, by the Common Fund. These include the
Bridging Interventional Development Gaps (BrIDGs) program; the NIH
Chemical Genomics Center (NCGC), which is part of the Common Fund's
Molecular Libraries and Imaging program; the Tissue Chips for Drug
Screening program and the Discovering New Therapeutic Uses for Existing
Molecules program, which are both part of the Common Fund's Regulatory
Science program; and the Extracellular RNA Communication program. For
all of these initiatives, there is ongoing coordination between NCATS
and Common Fund staff, with guidance from trans-NIH working groups.
Complementarity between the Common Fund and NCATS in how these programs
are currently conceptualized, managed, and led on behalf of the trans-
NIH community.
The fiscal year 2014 President's budget requests additional funding
for NCATS so that support for several of these programs can be shifted
from the Common Fund to NCATS.
Question. One of the newest entities within the NIH is the NCATS.
Could you provide the committee with an update on some of NCATS'
current activities and planned expenditures in fiscal year 2014? I am
especially interested in the Clinical Translational Science Awards
(CTSAs) program, which I believe the Institutes of Medicine is
currently reviewing at NIH's request. Vanderbilt University in
Nashville is the coordinating center for the 60 research institutions
linked by this program, which supports local and national research
communities to improve the quality and efficiency of all phases of
translational research. Going forward, how do you envision building on
the work of CTSA recipients to complement other NIH initiatives in
translational science? How do you see the CTSA program working with
Foundations, patient advocacy groups and industry?
Answer. To bring the benefits of science more quickly into patient
care, the NCATS was formed with the mission to catalyze the generation
of innovative methods and technologies that will enhance the
development, testing, and implementation of diagnostics and
therapeutics across a wide range of human diseases and conditions.
NCATS' mission includes strengthening the entire spectrum of
translational research--defined broadly to include the early steps
necessary to develop new therapeutics, devices and diagnostics from
basic discoveries, the steps necessary to establish real world
efficacy, and the research needed to improve the practical
implementation and dissemination of improved approaches to care.
NCATS will utilize a number of programs to accomplish its mission
across this translational spectrum. Extending the success of the CTSA
program in transforming the local and regional environment for
translational research to, in turn, transform the national environment
for translation will be a central component. In order to accomplish
this transformation across a broad spectrum of diseases and conditions,
NCATS will focus on collaboration in and across all of its programs.
Key partners will include, but are not limited to, other NIH
Institutes, Federal agencies, patient advocacy groups, professional
societies, foundations, healthcare systems, and a wide range of
commercial entities. NCATS will leverage and build on existing
relationships with many foundations, patient advocacy groups and
industry, as collaborators, advisors, committee members and program
partners.
NCATS engaged the Institute of Medicine (IOM) to review the CTSA
program and provide recommendations for any changes needed in the
program. The report was released at the end of June and NCATS is
reviewing the recommendations of this group as we work to evolve the
CTSA program within NCATS.
______
Questions Submitted by Senator Mark Kirk
Question. BrainGate is a promising technology. How does the
National Institutes of Health (NIH) plan to integrate promising
technologies like BrainGate--and other existing stroke research
priorities--with the proposed Brain Research through Advancing
Innovative Neurotechnologies (BRAIN) Initiative?
Answer. The BrainGate neural interface system is a promising type
of brain-computer interface intended to put prosthetic arms and other
assistive technologies under the control of people who are disabled
because of a stroke or other neurological disorder. Using BrainGate in
a controlled laboratory setting, a paralyzed woman was able to move a
robotic arm and take a sip of coffee on her own for the first time
since she had been paralyzed more than 14 years earlier. BrainGate
consists of sensors implanted in the brain that monitor signals from
nerve cells in a brain area that controls movement, and computer
software and hardware that translate these signals into digital
commands for assistive devices. A clinical trial, funded in part by the
NIH, is evaluating the safety and feasibility of this device.
The BRAIN initiative will advance the prospects for more effective
brain computer interface devices in two ways. First, BRAIN will develop
tools that will transform researchers' capabilities to monitor larger
numbers of brain cells, in a less invasive manner, more stably over
time. This addresses major limitations of the current generation of
brain computer interfaces, which monitor relatively few cells and rely
upon invasive electrodes that often do not maintain a stable signal
over time. Second, with the tools from BRAIN in hand, researchers will
learn to better understand the ``neural code'' by which brain circuits
control movement and perceive the environment. This will enable the
design of devices that interface with brain circuits more effectively
to provide precise and natural movement control and sensory feedback.
The potential for extraordinary long-term benefits of the BRAIN
Initiative is tantalizing, with transformative technologies for
recording nerve cells now in use or on the horizon, including those
that rely on optical signals. However, these technologies are currently
not suitable for use in humans, and laboratory research in animals,
including those with much simpler brains, will initially be a focus of
BRAIN. NIH is continuing to support the near-term development of brain
computer interfaces, such as BrainGate, as we also invest through the
BRAIN Initiative in research that will revolutionize the understanding
of the brain and its disorders in the future.
Question. Rehabilitation research is cross-cutting within NIH. What
is NIH doing to prevent duplication in research?
Answer. NIH's rehabilitation research efforts include a range of
studies from developing next generation prostheses and assistive
devices, to optimizing physical, cognitive, and combination drug
therapies. A number of NIH Institutes and Centers (ICs) support
extensive research related to medical rehabilitation.
Although multiple ICs are involved, they proactively work to
coordinate their activities and prevent duplication of efforts. For
example, the Eunice Kennedy Shriver National Institute of Child Health
and Human Development's National Center for Medical Rehabilitation
Research (NCMRR) supports research needed to enhance the health,
productivity, independence, and quality-of-life of people with
disabilities. The Center's role includes coordination of medical
rehabilitation research, and promoting research specific to the health
related problems of people with disabilities in order to capitalize on
advances occurring in the biological, behavioral, and engineering
sciences. The Center's work has been aided by a blue ribbon panel
formed in 2011 to focus on medical rehabilitation research at NIH. The
panel conducted an analysis of rehabilitation science activities within
the NCMRR and across the NIH to identify the most promising research
opportunities which was reported to the National Advisory Child Health
and Human Development Council.
In addition, NIH has an established record of identifying
scientific areas of potential overlap and developing trans-NIH
programs, activities, and policies to optimize the strengths and
expertise within each of the ICs and to ensure the complementarity of
their programs and activities. The Division of Program Coordination,
Planning, and Strategic Initiatives (DPCPSI) in the Office of the
Director works closely with the NIH Institutes and Centers (ICs) to
plan and coordinate trans-NIH research cross-cutting activities. As
part of this process, DPCPSI will work with all relevant ICs to conduct
a portfolio analysis designed to identify scientific gaps and areas of
sufficient investment.
DPCPSI's Office of Portfolio Analysis provides consultation and
training to NIH program staff in the use of portfolio analysis tools
that allow IC staff to identify gaps in specific research portfolios
and areas that are adequately funded across ICs. Such evaluation tools
provide data to enhance prioritization efforts of current and emerging
areas of research, and also prevent unnecessary overlaps and
duplication of effort.
Administrative processes are also in place to monitor for
scientific overlaps in funding opportunity announcements (FOAs) and in
grant applications. At the FOA stage, the new Guide Publishing System
allows ICs to review of funding opportunity announcements prior to
publication. When grant applications are received, duplicative
proposals can be identified at the receipt and referral stage and at
the peer review stage. After review, meritorious applications are
checked for other sources of support, including all existing and
pending financial resources, whether Federal, non-Federal, commercial
or organizational, to determine whether there may be budgetary,
scientific, or commitment overlap. This step is key to identifying and
eliminating duplicative proposals.
______
Questions Submitted to Dr. Story C. Landis
Question Submitted by Senator Tom Harkin
Question. Dr. Landis, when you add up the contributions from your
private sector partners--the Allen Institute for Brain Science (at
least $60 million/year), the Howard Hughes Medical Institute (at least
$30 million/year), and others--they're planning to contribute
approximately the same amount or more as the President is requesting.
Do you expect the same situation in future years of the initiative?
Answer. Each partner has a long-standing commitment to neuroscience
research and we do not anticipate that their contributions to the Brain
Research through Advancing Innovative Neurotechnologies (BRAIN)
Initiative will be a one-time event. However, details of the initiative
are still under development as part of a rigorous scientific planning
process, for which final recommendations are anticipated in the summer
of 2014. This plan will be widely shared with both the public and with
our BRAIN Initiative partners.
______
Questions Submitted to Dr. Richard J. Hodes
Questions Submitted by Senator Jerry Moran
Question. Dr. Hodes, the RAND Corporation recently released a
report that found that the cost of caring for all Americans with
dementia in 2010 was between $157 billion and $215 billion. By 2030,
the number of Americans with dementia is expected to more than double.
A few statistics:
--Medicaid payments alone are 9 times higher for those with
Alzheimer's compared to those without the disease.
--64 percent of Medicare beneficiaries in nursing homes over 65 years
old have Alzheimer's disease or other dementia and Medicare
pays approximately $11 billion a year for their care.
--Each dementia case costs between $41,000-$56,000 a year.
We know that these numbers will only increase as our population
ages. I support the National Institutes of Health (NIH) for many
reasons--the impact to health being paramount. But another key
component of my support is that I believe if we can find effective
treatments for diseases like Alzheimer's and dementia, we can not only
extend quality of life for patients, but reduce the cost of caring for
these patients in years to come. Could you discuss some of the research
projects the National Institute on Aging will fund if this proposal is
approved and the impact these projects could have on our Nation's
healthcare costs?
Answer. Pending availability of funds, the ongoing Alzheimer's
disease (AD) research supported by the National Institute on Aging
(NIA) will continue in 2014, along with several recently launched
efforts made possible with increased funding. These include:
--Whole genome sequencing to identify new genetic variants that
either increase risk (risk factors) or reduce risk (protective
factors) for AD (in collaboration with the National Human
Genome Research Institute).
--A treatment trial to test the effectiveness of intranasal insulin
in individuals with mild cognitive impairment or mild
Alzheimer's dementia on cognition and daily functioning.
--A 5-year prevention trial to test the ability of an antibody called
crenezumab to bind to and clear away abnormal amounts of
amyloid protein in the brain and prevent cognitive decline in
people with early-onset AD.
--Research to be funded in fiscal year 2013 and fiscal year 2014
under four 2012 Funding Opportunity Announcements supporting
drug discovery, development, and preclinical and clinical
testing for the treatment and prevention of Alzheimer's disease
and dementia.
In addition, recent scientific advancement suggests that some new
activities may be feasible. If so, we anticipate new activities in the
following areas in fiscal year 2014:
--Additional Drug Development and Testing.--This will include support
for drug repurposing and combination therapy, phase 2 (proof of
concept) drug trials for agents against currently known
therapeutic targets, and studies of possible agents against
not-yet-known therapeutic targets for AD.
--Non-Pharmacological Intervention Development.--We will focus on
advancing non-pharmacological interventions for the cognitive
and behavioral symptoms of AD and the design of approaches that
combine pharmacological and non-pharmacological treatments.
--Biomarkers of Disease Progression to Measure the Effects of
Potential Treatments.--We will test imaging and fluid
biomarkers for the assessment of disease-related pathology,
work to develop and validate sensitive measures to detect and
track the earliest clinical changes of AD, and develop and test
methods for the standardization of neuroimaging procedures and
data collection.
The issue of the impact of this research on healthcare costs is
highly complex. Alzheimer's disease treatment and care place an
enormous financial and economic burden on patients, their families, and
the healthcare system, as illustrated by the NIA-supported study from
the Rand Foundation noting that the costs of caring for people with
dementia in the United States in 2010 were between $159 billion and
$215 billion, and could double by 2040. Estimates of cost savings
resulting from an effective therapy need to account for a number of
factors, including the cost of the therapy itself, which could be
significant, or savings offset by other costs of providing care to
those surviving patients.
Question. Many diseases are increasingly common with older age.
What efforts is NIH making to understand the aging process and its
relationship to these diseases?
Answer. Age is a primary risk factor for many disabling diseases
and conditions, and NIH supports a robust program of research aimed at
understanding the relationship between aging and disease and
disability. Ongoing initiatives include:
--NIH Geroscience Interest Group.--The NIH Geroscience Interest Group
(GSIG) was established in 2012 to accelerate and coordinate
efforts to promote further discoveries on the common risks and
mechanisms behind age-related diseases and conditions by
developing a framework that includes multiple NIH Institutes.
By pooling resources and expertise, the GSIG identifies major
cross-cutting areas of research and proposes coordinated
approaches to identify hurdles and envision solutions. In
September 2012, the GSIG sponsored a workshop on inflammation
and age-related diseases, and this activity has led to a
Funding Opportunity Announcement on the subject, co-sponsored
by several NIH Institutes. As a way of gaining further input
from the research community, a larger-scale workshop titled
``Geroscience: Foundations for Delaying Chronic Disease and
Increasing Healthspan'' is planned for fall 2013. This two and
a half day forum will bring together 53 leaders from the fields
of aging and major chronic diseases.
--Nathan Shock Centers on the Basic Biology of Aging.--NIH supports
five Nathan Shock Centers on the Basic Biology of Aging. These
Centers provide leadership in the pursuit of basic research
into the biology of aging through a Research Development Core
which administers small start-up funds locally, and organizes
national annual meetings to highlight specific areas of
research. In addition, each Nathan Shock Center has several
specialized cores that provide services to other investigators.
The cores are different in each Center, depending on the
strengths of each Institution. Funding for the Nathan Shock
Centers is slated for renewal in fiscal year 2015.
--Interventions Testing Program (ITP).--This ongoing program, which
began in 2003, supports the testing of compounds with the
potential to extend the lifespan and delay disease and
dysfunction in a mouse model of aging. A number of
interventions, including foods, diets, drugs, and hormones, are
tested through the ITP, and some compounds, such as rapamycin,
have been found to increase not only lifespan, but health as
well. Further research is ongoing, and a parallel program has
been established to test interventions in the worm model
``Caenorhabditis elegans''.
Question. How might this understanding allow better treatment or
prevention?
Answer. A better understanding of the basic biochemical, genetic,
and physiological mechanisms underlying the process of aging and age-
related changes will provide insight as to how these changes become
risk factors for (or accompany) age-related disease and disability.
This, in turn, will suggest interventions that may increase both
lifespan and health span in older adults.
An example of basic discovery that may suggest pathways for
prevention of disease and disability is the exciting research being
conducted around cellular senescence and aging. Senescent cells no
longer divide but still function within the organism and until recently
scientists believed that they were very rare in living organisms and
would not play an active role in aging. However, NIH-supported
investigators recently found that high levels of senescent cells
actually do accumulate in many tissues in aged mice, and may be an
early marker of cancer--in fact, the earliest marker of cancer
described to date. In a separate study, removal of senescent cells in
mice delayed the onset of disease-related changes in skeletal muscle,
fat, and eye tissues. In addition, removing senescent cells later in
the life of the mice slowed the progression of already established age-
related disorders. While research on cell cultures has long suggested
that senescent cells have a role in aging, the nature of this
connection in live animals was less clear. The new finding suggests
that cell senescence may be a fundamental mechanism that drives aging,
and provides a clear target for interventions to prevent age-related
damage to cells and tissues.
Question. Dr. Hodes, as a nation, we invest a significant amount of
funding towards healthcare. What is the NIA doing--and what should the
NIA do--to expand and translate research on prevention and wellness for
our rapidly aging population?
Answer. Recent NIA-supported studies conducted by the National
Academy of Sciences have shown that although the United States spends
more on healthcare than any other nation, Americans are in poorer
health and live shorter lives than people in many other high-income
countries. This health disadvantage exists across the lifespan, from
birth to age 75. Many of the reasons behind these disparities appear to
be behavioral and social--for example, Americans are more likely to
engage in certain unhealthy behaviors, such as heavy caloric intake and
behaviors that increase the risk of fatal injuries. However, even
Americans who have health insurance, college educations, and higher
incomes who adopt healthy behaviors appear to be sicker than their
peers in other wealthy nations. The reasons for these disparities
remain unclear. NIA continues to support research to determine the
factors that contribute to premature mortality and lower disability
adjusted life years in the United States, as well as the prospects for
modifying such risk factors.
In addition, NIA supports a number of studies of interventions to
prevent disease and disability. For example, the ongoing Lifestyle
Interventions and Independence for Elders (LIFE) Study, a major
clinical trial comparing the effects of a moderate-intensity physical
activity program to a health education program on prevention of
mobility loss disability in older Americans, began in 2010. In
addition, NIA supports a number of studies exploring the effects of
exercise and physical activity on everything from mobility to mood and
cognition. NIA also supports studies of a variety of interventions for
health conditions common to old age. Ongoing studies include: the
ASPirin in Reducing Events in the Elderly (ASPREE) trial, designed to
determine whether the benefits of aspirin outweigh the risks in people
over age 70; testosterone supplementation to delay or prevent frailty
in older men; and an array of interventions for menopausal symptoms.
Translation of research findings related to healthy aging is an
important priority for the NIA. For example, we support 13 Edward R.
Roybal Centers for Translational Research in the Behavioral and Social
Sciences of Aging, which stimulate broadly based multidisciplinary
research that improves the health, wellbeing, and productivity of older
adults. The Roybal Centers focus on diverse topics including health and
mobility, disease and pain management, and decisionmaking and behavior
change.
NIA also supports a successful program of communication and health
education for older adults, their caregivers, and healthcare providers.
For example, recognizing the value of exercise, the NIA partnered with
the U.S. Surgeon General to launch its nationwide ``Go4Life'' campaign.
This program is designed to motivate older Americans to engage in
physical activity and exercise by becoming active for the first time,
returning to exercise after a break in their routines, or building
activity into daily routines. Go4Life offers exercises, motivational
tips, and free resources to help participants get ready, start
exercising, and keep going. The Go4Life campaign centers on an
interactive Web site (www.nia.nih.gov/go4life), which features an
evidence-based exercise guide in English and Spanish, exercise videos,
and more. The initial partners include a diverse group of public and
private Go4Life Team Members from major health and aging organizations
and agencies, and the Institute intensified program activities in 2012.
Further, NIA produces informative, evidence-based educational
materials for older adults, including ``Age Pages'' in English and
Spanish on a wide variety of topics of interest, as well as more in-
depth documents providing information and advice on an array of topics,
including healthy nutrition, planning for retirement, and end-of-life
care. Finally, NIA and the National Library of Medicine have created
NIHSeniorHealth.gov, a health information Web site tailored to the
specific cognitive and information needs of older Americans.
______
Questions Submitted to Dr. Harold E. Varmus
Questions Submitted by Senator Jerry Moran
Question. Dr. Varmus, I have read several news articles about the
impressive results being generated by the Cancer Genome Atlas project.
What is being done to ensure that the new information being
discovered about cancer genomes will have direct benefits for patients?
Answer. The unprecedented wealth of data generated by the Cancer
Genome Atlas (TCGA) is dramatically increasing our knowledge of the
range and combination of abnormalities that may be found in cancer and
refining our understanding of molecular pathways that control its
malignant behavior. With the long-term goal of improving diagnostic
precision and treatment outcomes for cancer patients, TCGA data are
being applied to an array of projects and programs in the U.S. and
abroad. For example, the National Cancer Institute (NCI) Cancer Target
Discovery and Development (CTD2) Network, which is a consortium of
investigators from many research institutions in the U.S., is
elucidating new targets for therapeutic attack in cancer and developing
means to inhibit these targets. TCGA data are also being used to
explore the relationship between germline genetic variation and the
molecular features of tumors that arise in various tissues.
TCGA data are widely available to qualified researchers through
public databases designed to protect patient privacy, and we are
continually striving to improve our management of these extremely large
datasets through enhanced computational methods. The TCGA team provides
extensive support to researchers who access TCGA data, including step-
by-step protocols for how to locate and apply TCGA data, as well as
preliminary data analysis to those who need assistance with
manipulating the raw data, in an effort to maximize the efficient and
effective use of the data. The large number of publications that use
TCGA data (almost 400 since 2008) and the number of grant applications
that include TCGA data (to date, more than 800) reflect the widespread
availability and broad utilization of TCGA data by the cancer research
community. In addition, the NCI is expanding its computational power in
various ways to cope more effectively with the rapidly growing data
sets from TCGA and other endeavors in cancer genomics.
Pursuing the genetic foundations of many cancers is a vital element
of NCI's current research, comprising a substantial proportion of the
institute's research portfolio. A principal task in the years ahead,
for NCI and for the entire cancer research enterprise, will be to
capitalize on the information developed through TCGA by supporting
additional studies that validate and extend our understanding of--and
ability to use to diagnostic, prognostic, and therapeutic advantage--
the critical roles for specific genomic changes in tumors. Ultimately,
these efforts can be expected to lead to more precise classification of
cancers and more effective interventions that improve outcomes for
patients.
Question. For example, are the data and the methods being
incorporated into the design of NCI's clinical trials?
Answer. NCI has recently consolidated a number of its genomics
initiatives--including TCGA and several pediatric cancer initiatives,
most notably TARGET (Therapeutically Applicable Research to Generate
Effective Treatments), as well as CTD2--into a single Center for Cancer
Genomics. The new Center is working with other components of NCI and
with other investigators in addition to those directly involved in TCGA
to ensure that research findings are applied to developing new
diagnostics and therapeutics that can be integrated into medical
practice. For example, new therapeutic studies are now being designed
by our clinical trials groups in conjunction with TCGA staff to match
the genotypes of advancing cancers with targeted drugs and to seek
genomic explanations for unexpectedly good responses to existing drugs
or to not yet approved agents used in clinical trials; these studies
will use methodology developed in conjunction with TCGA projects. In
addition, several clinical trials have already been established based
directly on TCGA data, and we expect additional trials to be initiated
as TCGA continues to generate new information about potential targets
for cancer treatment strategies.
We anticipate that our growing understanding of the molecular
events that drive cancer development and distinguish one cancer type
from another will have a marked effect on the way future clinical
trials are designed. The new knowledge should enable the NCI
cooperative groups that do most of our clinical trials to run smaller,
more precise clinical trials with greater likelihood of therapeutic
success. In addition, we can expect an increasing number of clinical
trials that are somewhat tumor site-agnostic: directed at molecular
vulnerabilities that are common to cancers that may arise in different
tissues.
______
Questions Submitted by Senator Richard C. Shelby
Question. Dr. Varmus, last year you expressed concerns about
legislation that originally would have required the National Cancer
Institute to spend $887.8 million of its budget on pancreatic cancer
research. I share the concern about earmarking disease specific
research. I believe science should dictate funding and a legislative
mandate on disease specific research would lead to a slippery slope of
Congress moving into the driver seat of determining how the National
Institutes of Health (NIH) research funding is spent. That said, the
current Administration has attempted to earmark NIH funding in the past
for both cancer and Alzheimer's disease research.
How can it be wrong for Congress to direct funding, but not for the
Administration to do so?
Answer. NIH is comprised of 27 institutes and centers (IC) mostly
organized by specific diseases, organs, and stages of life. These
entities come together to seek the fundamental knowledge about the
nature and behavior of living systems and the application of that
knowledge to enhance health, lengthen life, and reduce illness and
disability.
Historically, Congress has given NIH the flexibility to drive
research and this flexibility has nurtured scientific advances and
development of means to prevent and treat diseases more effectively. A
baby born today can look forward to an average lifespan of nearly 79
years, nearly three decades longer than a baby born in 1900. For
example, U.S. cancer death rates are falling more than 1 percent each
year. and age-adjusted death rates from heart disease and stroke have
fallen more than 60 percent in the last half-century. Thanks to anti-
viral therapies developed by NIH funded researchers, HIV-infected
people in their 20s can expect to live to age 70 and beyond.
NIH will continue invest research funds based on scientific
opportunities and public health needs. As part of the Executive Branch,
the NIH works closely with the Administration to plan future research
efforts. The Administration's past interest in increased spending on
cancer research and more recent interest in Alzheimer's disease (AD)
research both came at a time of enhanced scientific opportunity and
public health need for progress against these devastating and common
diseases. About half of men and a third of women in the U.S. will have
a cancer diagnosis in their lifetimes, and cancer is the second most
common cause of death. Moreover, research over the past three decades
has transformed our conception of the disease, creating opportunities
for rapid advances Thus we have learned that cancer is a disease of the
genome, that it's not just one but many diseases, and that investments
to use the new tools of genomics are likely to lead to rapid progress
in the diagnosis and treatment of those several diseases. For example,
as drugs are developed that target certain mutations, doctors will be
able to use information about the molecular profile of a patient's
tumor to assess whether a given drug is likely to be effective. Genomic
knowledge can also be used to decide against a particular treatment, if
the appropriate target mutations are not in play, thus sparing a
patient the costs, waste of time, and side effects of a drug that is
not likely to help them.
The number of individuals with AD is expected to increase
dramatically as the population ages. The U.S. Census Bureau estimates
that the people 65 years and older will double to about 72 million
during the next 20 years. As the population ages, the medical and
treatment expenses associated with AD will continue to increase and
impose a significant economic burden to society and the government. At
the time the Administration announced the additional funding for AD,
NIH seized the opportunities to expand on several AD advances. NIH
supported researchers discovered that higher amounts of the brain
amyloid deposits in dementia-free individuals were associated with an
increased risk of developing dementia over time, making it a possible
preclinical sign of disease even among individuals who appear mentally
normal. In addition, NIH supported researchers developed a method of
testing for the known biomarkers for AD in the cerebrospinal fluid.
With these discoveries, NIH hopes to help diagnosis individuals with AD
in order to initiate treatment efforts early and delay the progression
of AD.
Question. It is my understanding that you had numerous concerns
about authorizing legislation proposed last year that would have
specified an amount of funding for pancreatic cancer. Can you discuss
some of those concerns?
Answer. The National Cancer Institute (NCI) raised serious
objections last year to a legislative proposal (a version of H.R. 733,
filed originally on February 16, 2011, ``to provide for a Pancreatic
Cancer Initiative''). However, our objections were directed largely
against a new methodology that would have altered how NCI funds grant
applications.
In this instance, the legislation would have required that the
Secretary of Health and Human Services convene a group, composed almost
entirely of pancreatic cancer researchers, to recommend which grant
applications should be funded. This would have created an unfortunate
precedent for many groups to ask for similar privileges, a situation
that would have been unworkable and damaging. Fortunately, this and
several other objectionable elements were removed from H.R. 733 before
its eventual approval as the Recalcitrant Cancers Act.
Although we objected to the bill in question largely on other
grounds, the NCI generally disapproves of mandates to spend specific
amounts of money on individual cancers. This is so for several reasons.
First, it is difficult to determine an exact number for disease-
specific spending: some studies address multiple cancers; many are
aimed at fundamental cell processes that are relevant to most or all
cancers; and some grants support training, technology development, and
other infrastructural issues that cannot be classified. More
importantly, history has supported the argument for supporting the best
science, rather than meeting a fiscal quota for each disease type. It
is common for studies of one type of cancer to provide unanticipated
insights into another type or for studies of the basic features of
cancer to illuminate our understanding of a variety of cancers. For
example, investment in a rare disease, retinoblastoma, was critical for
the discovery of tumor suppressor genes, a class of genes that is
affected in essentially every cancer type. Similarly, work on an animal
model of neuroblastoma led to the discovery of an oncogene, HER2, which
is targeted by antibodies now widely used in the treatment of breast
cancer. What has worked best is the support of experiments that pursue
the most inviting scientific opportunities. Of course, the NCI is
attentive to its patterns of spending on many types of cancer,
especially with regard to clinical research; but rigid prescriptions
for funding levels limit the Institute's capacity to support the most
productive work and respond quickly to new developments in cancer
science.
SUBCOMMITTEE RECESS
Senator Harkin. The hearing of the Labor, Health and Human
Services Subcommittee is adjourned. Thank you again all very
much.
[Whereupon, at 4:20 p.m., Wednesday, May 15, the
subcommittee was recessed, to reconvene subject to the call of
the Chair.]