[Senate Hearing 115-]
[From the U.S. Government Publishing Office]





 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2018

                              ----------                              


                        WEDNESDAY, MARCH 8, 2017

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 10:30 a.m., in room SD-138, Dirksen 
Senate Office Building, Hon. Roy Blunt (chairman) presiding.
    Present: Senators Blunt, Cochran, Alexander, Moran, Rubio, 
Murray, Durbin, and Leahy.

                 SAVING LIVES THROUGH MEDICAL RESEARCH


                 opening statement of senator roy blunt


    Senator Blunt. The Appropriations Subcommittee on Labor, 
Health and Human Services, Education, and Related Agencies will 
come to order.
    Good morning. I want to thank our witnesses for appearing 
before this subcommittee today. In the next few years as we 
continue to confront difficult spending choices, we really have 
to continue, in my view, to firmly establish our Federal 
commitment to the National Institute of Health (NIH).
    Since its founding, the NIH has funded research to raise 
life expectancy, to lower healthcare costs, and to improve the 
quality of life for all Americans.
    In the 80 years since Congress established the National 
Cancer Institute, we've gone from crude treatments with grim 
prognosis to a place where we know much more about what we are 
dealing with and how to deal with it. And we are going to hear 
today some future projections of how that even advances in a 
more dramatic way.
    Since the 1940s, the rate of cardiovascular deaths have 
dropped 60 percent thanks to effective treatments, a lot of 
which involved NIH funded research. These are really two great 
examples, both in cancer and in cardiovascular disease, of what 
happens when you have the kinds of medical breakthroughs that 
we've seen and I think can see in even greater numbers.
    In the past year, NIH funded the development of an 
artificial pancreas that would be life changing if you have 
Type I diabetes. They have discovered biomarkers that were 
unique to two different prostate cancer stages and decoded the 
structure of the Zika virus.
    We need to remember that this progress didn't occur on its 
own. It happened because of generations of researchers funded 
largely by the U.S. Government through the NIH tirelessly 
worked to discover the science that led to these treatments and 
cures. Federal funding was an essential component of that 
progress and has advanced the understanding of disease, raised 
life expectancy, and improved quality of life for patients and 
their families.
    Last year for the first time in over a decade, the Labor/
HHS Appropriations Bill significantly increased funding for 
NIH. This $2 billion increase allowed the NIH to fund 1,147 
more grants nationwide than they would have funded otherwise. 
Funding for NIH research in my home State increased by $37.4 
million or 8 percent as we saw just about that same size 
increase in overall NIH funding.
    Consistent, sustained increases in funding are critical for 
biomedical researchers as they undertake the complex multiyear 
studies necessary to pursue new treatments. Consistent funding 
is also essential if we are going to encourage young 
researchers. We are going to hear some about that today, as 
well to really believe that they can and will be able to make a 
real difference in research.
    By the way, a pattern has to first happen in the second 
year. And I want to thank Senator Murray for her support and 
leadership as we, again, finish the bill that is still pending 
before the Congress to add another $2 billion to the basic 
research funding at NIH. The fiscal year 2016 funding increase 
cannot and should not be seen as a one-time thing or even 
towards some goal that is anywhere short of funding research as 
long as there's research that is promising to be funded.
    We do know that the scientific advances that will be made 
in the next 10 years can make a real difference in people's 
lives and make a real difference in overall healthcare cost. 
They'll make a real difference in taxpayer funded healthcare 
costs. We need to be committed in that regard. And certainly, 
Senator Murray has been and we've been able to work together on 
this. Senator Murray, I would like to turn to you for your 
opening remarks.
    [The statement follows:]
                Prepared Statement of Senator Roy Blunt
    Good morning. I want to thank our witnesses for appearing before 
the Subcommittee today.
    In the next few years, as we continue to confront difficult 
spending choices, we must continue to firmly establish our Federal 
commitment to the National Institutes of Health (NIH). Since its 
founding, the NIH has funded research to raise life expectancy, lower 
healthcare costs, and improve the quality of life for all Americans. In 
the 80 years since Congress established the National Cancer Institute, 
crude treatments and grim prognoses have been replaced by 
individualized treatments and sophisticated diagnostics. Since the 
1940s, the rate of cardiovascular disease deaths has dropped 60 percent 
thanks to effective treatments developed by NIH-funded research. And 
these great strides are just two examples of thousands of medical 
breakthroughs. In just the past year, NIH funded the development of an 
artificial pancreas that would be a life-changing advance for many 
people with type 1 diabetes; discovered biomarkers that were unique to 
two different prostate cancer stages; and decoded the structure of the 
Zika virus.
    We should remember that this progress did not occur on its own. It 
happened because generations of researchers, funded largely by the U.S. 
Government through the NIH, tirelessly worked to discover the science 
that led to these treatments and cures. Federal funding was an 
essential component of the progress that has advanced the understanding 
of disease, raised life expectancy, and improved the quality of life 
for patients and their families.
    Last year, for the first time in over a decade, the Labor/HHS 
Appropriations bill significantly increased funding for the NIH. This 
$2 billion increase allowed the NIH to fund 1,147 more grants 
nationwide. Funding for NIH research in my home State of Missouri has 
increased $37.4 million or 8 percent. Consistent, sustained increases 
in funding are critical for biomedical researchers as they undertake 
the complex, multi-year studies necessary to pursue new treatments and 
cures. But the way to begin a pattern is in the second year, and, with 
my thanks to Senator Murray for her support, this fiscal year we were 
able not only to pass the first bipartisan Labor/HHS bill out of 
Committee in 7 years, but also to increase NIH funding by another $2 
billion.
    The fiscal year 2016 funding increase cannot and should not be a 
one hit wonder. We should not point to that and believe we have 
accomplished our goal. We must remain focused on establishing a pattern 
of responsible investment through the appropriations process. We do not 
know the scientific advances that will be made in the next 10 years, 
but we do know that if we keep investing in NIH, they will keep making 
life-saving breakthroughs. That is why funding NIH, every year, through 
the appropriations process, provides the opportunity to capitalize on 
and enhance the discoveries made by the research community and ensure 
we are funding the right programs with the most scientific promise.
    I look forward to hearing from today's witnesses who understand, 
first hand, the importance of NIH funding and the impact this funding 
has on the lives of every American.
    Thank you.

                   STATEMENT OF SENATOR PATTY MURRAY

    Senator Murray. Well, thank you very much, Mr. Chairman, 
for calling this hearing and I want to thank all of our 
witnesses for traveling here today and being with us. I look 
forward to hearing what you have to say.
    The investments that we make in this subcommittee help keep 
families and communities healthy by supporting programs that 
reduce infant mortality, train our doctors and nurses, provide 
care in rural communities, and prevent the spread of infectious 
diseases and so much more.
    The NIH accounts for the largest share of our 
subcommittee's resource and its work is vital to all those 
efforts. The basic research it supports leads to the 
discoveries and breakthroughs that give hope to those living 
with chronic and life threatening disease and bolster economic 
growth and competitiveness.
    Today NIH researchers are taking advantage of the 
achievements made in human genetics, imaging technology, and 
other fields to advance our understanding of diseases like 
cancer and Alzheimer's. Its precision medicine initiative is 
using the genetics of cancer to find effective therapies while 
its BRAIN Initiative is revolutionizing our understanding of 
the human brain.
    We are on the cusp of major breakthroughs for so many 
illnesses that cost lives and hurt families each day.
    But now there are efforts that actually would put millions 
of Americans' access to these advanced treatments at risk and 
there is a very real threat to this committee's ability to fund 
future increases NIH to sustain its research efforts.
    Republicans are, as we speak, rushing to dismantle the 
Affordable Care Act which expanded health coverage to 20 
million Americans and ended the restrictions on preexisting 
conditions and lifetime caps that previously forced many of 
those who had serious illnesses to choose between bankrupting 
their families or foregoing treatment.
    The House Republican Trump Care Bill would take us back to 
those bad days, meaning people across the country could lose 
access to the actual treatments that NIH research makes 
possible.
    When I consider what that would mean, I think of one of my 
guests at the President's address last week, Marci Owens. She's 
from Seattle and her mother died at the age of 27. Her mother 
was 27 years old. She became ill. She lost her job and she lost 
her health insurance, and eventually died.
    And I am very deeply troubled that some Republicans want to 
return it to a time when there are more stores like Marci's.
    I recently heard from the wife of a father in a self 
employed contractor named Richard in my home State of 
Washington who, thanks to the ACA, had health insurance through 
Medicaid when he was diagnosed with an aggressive and rare form 
of leukemia.
    His illness didn't respond to the conventional therapy, so 
his doctors with the Seattle Cancer Care Alliance enrolled him 
in a CAR T cell immunotherapy trial in a last-ditch effort. 
Richard is now in remission with real hope for a long-term 
cure. And his family says the immunotherapy treatment saved his 
life. Absent the ACA, Richard's wife, Jennifer, says she 
believes she would now be raising their two children on her 
own.
    I am also concerned by the details of the President's 
budget that the administration recently chose to make public. 
Cutting non-defense spending by $54 billion would require 
devastating cuts to the education, health, and training 
programs that this subcommittee funds. And I don't see how NIH, 
which accounts for 20 percent of the funding in the bill will 
avoid being affected. I know members on both sides of the aisle 
here agree on the importance of medical research, so this is 
not a partisan issue.
    Just last December, Democrats and Republicans were able to 
come together to establish a new $4.8 billion funding stream 
for NIH and I want to thank the chairman for his focus on that 
last year to help accelerate medical research efforts. That was 
an important step forward as was the bipartisan spending bill 
that this subcommittee wrote last spring that would provide 
additional funding for NIH and other priorities in 2017. 
Unfortunately, we know now the fate of that spending bill is 
uncertain.
    Patients and families across the country are waiting. 
They're hoping for better cures and treatments as well as for 
help with the other challenges they face, whether it is quality 
child care or paying for college or getting care when they're 
sick. And here in Congress, I hope we can do our part to 
deliver. So thank you very much, Mr. Chairman.
    [The statement follows:]
               Prepared Statement of Senator Patty Murray
    Thank you, Mr. Chairman, for calling this hearing.
    And welcome Doctors Eberlein, Grabowski, Sasser, and Schultz-
Cherry.
    I look forward to the discussion this morning.
    The investments we make here in this subcommittee help keep 
families and communities healthy, by supporting programs that:
  --reduce infant mortality,
  --train doctors and nurses,
  --provide care in rural communities,
  --prevent the spread of infectious diseases,
  --and so much more.
    The NIH accounts for the largest share of our subcommittee's 
resources, and its work is vital to these efforts.
    The basic research it supports leads to the discoveries and 
breakthroughs that:
  --give hope to those living with chronic and life-threatening 
        disease;
  --and bolster economic growth and competitiveness.
    Today, NIH researchers are taking advantage of the achievements 
made in human genetics, imaging technology, and other fields to advance 
our understanding of diseases like cancer and Alzheimer's disease.
    Its Precision Medicine Initiative is using the genetics of cancer 
to find effective therapies, while its BRAIN Initiative is 
revolutionizing our understanding of the human brain.
    We're on the cusp of major breakthroughs for so many of the 
illnesses that cost lives and hurt families each day.
    But now, there are efforts that would put millions of Americans' 
access to these advanced treatments at risk, and there is a very real 
threat to this Committee's ability to fund future increases in NIH to 
sustain its research efforts.
    Republicans are, as we speak, rushing to dismantle the Affordable 
Care Act, which expanded health coverage to 20 million Americans, and 
ended restrictions on pre-existing conditions and lifetime caps that 
previously forced many of those with serious illnesses to choose 
between bankrupting their families, or foregoing treatment.
    The deeply harmful House Republican Trumpcare bill would take us 
back to those bad days--meaning people across the country could lose 
access to the treatments that NIH research makes possible.
    When I consider what that would mean, I think of one of my guests 
at the President's joint address, Marci Owens. Marci is from Seattle, 
and her mother died at age 27 after she became ill, then lost her job 
and the health insurance that came with it.
    I'm deeply troubled that some Republicans want to return to a time 
when there were more stories like Marci's.
    I recently heard from the wife of a father and self-employed 
contractor named Richard in my home State of Washington who, thanks to 
the ACA, had health insurance through Medicaid when he was diagnosed 
with an aggressive and rare form of leukemia.
    His illness did not respond to conventional therapies, so his 
doctors with the Seattle Cancer Care Alliance enrolled him in a CAR-T-
cell immunotherapy trial in a last ditch effort.
    Richard is now in remission, with real hope for a long-term cure.
    His family says the immunotherapy treatments saved his life. Absent 
the ACA, Richard's wife Jennifer believes she would now be raising 
their two children on her own.
    I'm also concerned by the details of the President's budget that 
the Administration recently chose to make public. Cutting non-defense 
spending by $54 billion would require devastating cuts to the 
education, health and training programs our subcommittee funds.
    And I don't see how NIH, which accounts for twenty percent of the 
funding in the bill, can avoid being affected.
    I know members on both sides of the aisle agree on the importance 
of medical research--so this is not a partisan issue.
    Just last December, Democrats and Republicans were able to come 
together to establish a new $4.8 billion funding stream for NIH in the 
CURES Act to help accelerate medical research efforts.
    That was an important step forward--as was the bipartisan spending 
bill this subcommittee wrote last spring that would provide additional 
funding for NIH and other priorities in 2017.
    Unfortunately, the fate of that spending bill is now uncertain.
    Patients and families across the country are waiting and hoping for 
better cures and treatments, as well as for help with the other 
challenges they face, be it:
  --finding quality child care,
  --paying for college,
  --or being able to get care when they are ill--and here in Congress, 
        we should do our part to deliver.
    Thank you, Mr. Chairman.

    Senator Blunt. Thank you, Senator Murray. We are always 
glad to have the chairman of the full committee with us. 
Senator Cochran, thank you for being here today. Do you have 
any comments you would like to add?

                   STATEMENT OF SENATOR THAD COCHRAN

    Senator Cochran. Mr. Chairman, thank you. I am pleased to 
see that we've empaneled some outstanding witnesses today to 
help us understand better the practical consequences of what we 
do here. And that includes appropriating dollars earmarked--
excuse me--but earmarked for medical research. And I hope you 
won't disagree with our generosity.
    Senator Blunt. Thank you, Mr. Chairman. And I am pleased 
that we have the other members of the committee here and others 
will be coming.
    We have great witnesses today. I am pleased to welcome 
them. Dr. Timothy Eberlein is the director of the Siteman 
Cancer Center in St. Louis, one of the largest cancer centers 
in the country. He's also Surgeon-in-Chief at Barnes-Jewish 
Hospital. Dr. Thomas Grabowski is the Director of the Memory 
and Brain Wellness Center and Alzheimer's Disease Research 
Center at the University of Washington. Dr. Stacy Schultz-
Cherry is a member of the Department of Infectious Diseases at 
St. Jude's Research Hospital. And Dr. Jennifer Sasser is an 
assistant professor at the University of Mississippi Medical 
Center.
    We look forward to your testimony.
    Dr. Eberlein, we will start with you.
STATEMENT OF TIMOTHY J. EBERLEIN, M.D., DIRECTOR, ALVIN 
            J. SITEMAN CANCER CENTER, WASHINGTON 
            UNIVERSITY SCHOOL OF MEDICINE IN ST. LOUIS, 
            SURGEON-IN-CHIEF, BARNES-JEWISH HOSPITAL
    Dr. Eberlein. Mr. Chairman and members of the subcommittee, 
thank you for the opportunity to appear before you to discuss 
how investments in biomedical research save lives every day 
through the development of new therapies and treatments. Thank 
you, Chairman Blunt, Chairman Cochran, and Ranking Member 
Murray, and the full subcommittee for your leadership in 
working to ensure that the Federal Government makes significant 
and sustained investments in biomedical research and for 
continuing to make NIH a priority in a challenging Federal 
judgment environment.
    Our patients are seeing the benefits of Federal investments 
in research. Washington University was not only a member of the 
Human Genome Project, but we have used that expertise to 
pioneer the sequencing of cancer genomes. The ability to 
identify the genetic difference between healthy and cancerous 
tissues allowed us to apply this research to the clinical 
setting.
    Today we are performing clinical trials that use state of 
the art genomic analysis to determine precision treatments in 
patients with leukemia, breast, lung, and other tumors. An 
additional strategy is to use genomic mutational analysis of an 
individual's cancer to treat many solid tumors, such as breast, 
brain, melanoma, lung, and head and neck cancers using a 
vaccine tailored to eradicate the patient's specific tumor with 
minimal side-effects and morbidity.
    These clinical trials are examples that embody the goals of 
the Cancer Moonshot and the Precision Medicine Initiative, 
where we target treatments to the unique genetic 
characteristics of the patient and their disease.
    In my own practice, I treat patients with breast cancer. 
Traditionally, we have operated on premenopausal patients who 
have early stage breast cancer and then treat them with 
radiation therapy and chemo therapy. But we know that 
approximately four out of five of these patients might be cured 
with surgery and radiation therapy alone.
    The scientific challenge is that we don't yet know how to 
distinguish between the 20 percent who need additional 
chemotherapy from the 80 percent that don't. Can you imagine 
for a moment what that would mean for patients if we were able 
to make this determination--how patient's lives would improve, 
the cost of their care would decline if we avoided unnecessary 
therapy in four out of five of these cases? As we continue to 
develop our genomic understanding of cancer, I am confident we 
can get to a point where affordable personalized cancer 
treatments will be widely available.
    Advances such as these are why we have been successful in 
reducing cancer mortality by 25 percent since 1991. And for 
children, an even more dramatic reduction of 66 percent between 
1970 and 2014. The reduction in mortality, especially for 
children, is a direct result of improvements in treatment, 
treatments largely discovered through investigations made 
possible through grants from the NIH.
    Sustained appropriations with increased funding to advance 
novel discoveries are responsible for the dramatic examples and 
improvement of life expectancy of patients with cancer in the 
United States. These investments have allowed us to understand 
the fundamental biology behind the disease and then to develop 
important strategies to develop therapies and cures.
    What may be even more important, however, than the actual 
research, is the fact that virtually every scientist--whether 
in academia or industry--likely benefitted at some stage in 
their career by training at the National Institutes of Health 
like I did or through the utilization of NIH training grants 
and career development awards. This training equips scientists 
with the skills needed to develop 21st century cures and it 
represents an investment for which the country will reap 
benefits for decades to come.
    Thank you for the opportunity to speak today and I look 
forward to answering any questions you may have.
    [The statement follows:]
            Prepared Statement of Timothy J. Eberlein, M.D.
    Mr. Chairman and members of the subcommittee, thank you for the 
opportunity to appear before you to discuss how investments in 
biomedical research save lives every day through the development of new 
therapies and treatments.
    My name is Timothy J. Eberlein. I am an actively practicing 
physician and also serve as the Chairman of the Department of Surgery 
at the School of Medicine at Washington University in St. Louis. I also 
serve as the Director of the Alvin J. Siteman Cancer Center.
    Thank you, Chairman Blunt and Ranking Member Murray, for the 
opportunity to speak to the Subcommittee today, and for your leadership 
in working to ensure that the Federal Government makes a significant 
and sustained investment in biomedical research. I also want to thank 
the full Subcommittee for your work in providing substantial new 
resources for the National Institutes of Health and for continuing to 
make NIH a priority in a challenging Federal budget environment.
    Our cancer center is a joint venture of Washington University and 
Barnes-Jewish Hospital in St. Louis, Missouri. We are the only NCI-
designated comprehensive cancer center in the State of Missouri, and 
our 450 physicians and scientists care for over 50,000 cancer patients 
every year, patients who come to St. Louis from Missouri, surrounding 
States and across the Nation.
    Our patients are seeing the benefits of Federal investments in 
research. Washington University was highly involved in the Human Genome 
Project, contributing roughly 25 percent of the final code. We have 
used that expertise to pioneer the sequencing of cancer genomes, 
allowing us to identify the genetic differences between healthy and 
cancerous tissues. As our scientific understanding has advanced, we 
have sought to apply this research to the clinical setting. One 
illustrative example involves Dr. Lukas Wartman, an oncologist and 
leukemia survivor, who experienced a second relapse of his disease 
while a fellow at Washington University. Researchers performed a 
detailed analysis of Lukas's cancer genome, and they found a gene which 
was expressing at a much higher level than normal. The research team 
then identified an existing drug typically used to treat kidney cancer, 
which targets tumors with this specific gene. Through this precision 
therapy, Dr. Wartman's disease went into remission, further enabling 
him to undergo a stem cell transplant. He now is working to care for 
cancer patients, and under his leadership, we have established a 
multidisciplinary Genomics Tumor Board that meets regularly to identify 
patients who might benefit from genome sequencing. Dr. Wartman embodies 
the idea behind the Cancer Moonshot and the Precision Medicine 
Initiative, where we target therapies and treatments to the unique 
genetic characteristics of the patient and their disease.
    Utilizing sophisticated genomic analysis, we are on the cusp of 
fundamentally changing how we think about treating cancer by using 
targeted therapies that avoid unnecessary expensive treatments. By 
combining genomic mutational analysis of an individual's cancer, we are 
now doing clinical trials that treat many solid tumors such as breast, 
brain, melanoma, lung and head and neck cancers using a vaccine 
tailored to eradicate the patient's specific tumor with minimal side-
effects and morbidity. Another opportunity comes through the use of 
nanoparticles to deliver therapies. Multiple myeloma is a cancer of the 
bone marrow that responds initially to chemotherapy, but the cancer 
usually recurs and becomes more resistant to treatment. We have had 
drugs that should eradicate the disease, but they tend to degrade once 
administered to the patient. Putting these drugs into nanoparticles, 
however, we are able to target the myeloma cancer cell, eradicating it 
with minimal side effects. Each of these novel clinical trials occurred 
at our cancer center funded through investigator-initiated research 
made possible by the NIH.
    In my own practice, I treat patients with breast cancer. 
Traditionally, we have operated on pre-menopausal patients who have 
early stage breast cancer, and then treat them with radiation therapy 
and chemotherapy. However, we know that approximately four out of five 
of these patients might be cured with surgery and radiation therapy 
alone. The scientific challenge is that we do not yet know how to 
distinguish between the 20 percent who need the additional chemotherapy 
from the 80 percent who don't. Can you imagine for a moment, what that 
would mean to patients if we were able to make this determination--how 
their lives would improve if they were not subjected to the side-
effects of chemotherapy? Can you imagine how the cost of their care 
would decline, if we avoided unnecessary therapy in four out of five of 
these cases? As we continue to develop our genomic understanding of 
cancer, I am confident we can get to the point where affordable 
personalized cancer treatments will be widely available but we need 
sustained, stable Federal support for research to get us there.
    Another challenge I face in the operating room is being able to 
distinguish between cancerous and healthy tissue, and knowing exactly 
how much tissue to remove. Dr. Samuel Achilefu, a Washington University 
professor of radiology, has developed a set of goggles that help 
surgeons see and remove cancerous tumors as small as 1 mm in diameter, 
the thickness of about 10 sheets of paper. After a dye is injected into 
a patient's tumor, the cancerous cells ``glow'' when bathed in infrared 
light and viewed by the goggles. Dr. Achilefu's lab is also 
investigating phototherapy, killing cancer with light, through a new 
approach that utilizes already available radiopharmaceutical drugs that 
can create a light source within tumor cells. The light stimulates 
light-sensitive molecules that have been delivered to the cancer cells, 
converting them into highly toxic drugs. The advantage of this strategy 
is that it minimizes the impact on neighboring healthy tissue, which 
could lead to reduced side effects and better outcomes overall.
    Advances such as these are why we have been successful in reducing 
cancer mortality by 25 percent since 1991.\1\ The change in mortality 
in children has been even more dramatic, with the death rates among 
those aged birth to 19 having dropped 66 percent between 1970 and 
2014.\2\ I am particularly heartened by this progress with children. 
Adults have a greater ability to modify their behaviors that can lead 
to cancer--such as smoking or unhealthy diet. Children typically do not 
control the environment or the lifestyle decisions that can lead to 
their cancer. Thus, the reduction in mortality for children is a direct 
result of improvements in treatment-treatments largely discovered 
through investigations made possible through grants from the NIH.
---------------------------------------------------------------------------
    \1\ Siegel, R. L., K. Miller, A Jemal ``Cancer Statistics, 2017.'' 
CA: A Cancer Journal for Clinicians. January/February 2017. p. 18.
    \2\ Ibid. p. 27.
---------------------------------------------------------------------------
    Sustained appropriations with increased funding to advance novel 
discoveries and insights are responsible for the dramatic examples and 
improvement of life expectancy of patients with cancer in the United 
States. These investments have allowed us both to understand the 
fundamental biology behind disease and then to develop the strategies 
needed to develop therapies and cures. What may be even more important 
than the actual research, is the fact that virtually every scientist--
whether in academia or industry--likely benefitted by training through 
the National Institutes of Health either by training in Bethesda, like 
I did, or through utilization of NIH training grants and/or career 
development grants. The reach of this funding in providing jobs and 
sustaining careers is monumental. But, even more critical, this 
training equips scientists with the skills needed to develop 21st 
Century cures. By equipping our Nation's best and brightest minds to 
tackle these incredibly difficult problems, we are making an investment 
for which the country will reap benefits for decades to come.
    Thank you again for the opportunity to speak today, and I look 
forward to answering any questions you may have.

    Senator Blunt. Thank you, Dr. Eberlein. Dr. Grabowski.
STATEMENT OF THOMAS J. GRABOWSKI, JR., M.D. DIRECTOR, 
            MEMORY AND BRAIN WELLNESS CENTER, 
            ALZHEIMER'S DISEASE RESEARCH CENTER, 
            INTEGRATED BRAIN IMAGING CENTER, UNIVERSITY 
            OF WASHINGTON, SEATTLE
    Dr. Grabowski. Good morning, Chairman Blunt, Chairman 
Cochran, Ranking Member Murray, my Senator, and distinguished 
members of the subcommittee. Thank you for the opportunity to 
speak with you today about the value of medical research, 
something I do every day, and the pivotal role that NIH funding 
plays in our efforts to counter Alzheimer's disease.
    My name is Tom Grabowski. I am a neurologist at the 
University of Washington, where I direct our clinical and 
research Center for Alzheimer's Disease and related memory 
disorders. My own research focuses on advanced brain imaging 
approaches in neurodegenerative disease.
    Some five million Americans have Alzheimer's dementia, 
including one of nine people over age 65. Alzheimer's dementia 
has outsized emotional and material impacts on entire families. 
And it is the rare person whose circle has not been affected in 
some way by this disease. Alzheimer's is the only leading cause 
of death in 2017 that can't be cured, prevented, or even 
slowed. Consequently, increasing numbers of people are living 
and dying with Alzheimer's dementia, and the numbers are set to 
more than double and even triple by 2050.
    Alzheimer's dementia is a relatively late consequence of a 
disease process that has gone on in the brain for 15 years or 
more. This long pre-symptomatic phase is our window of 
opportunity for intervention. The National Plan to Address 
Alzheimer's Disease that guides our research efforts has an 
overarching first goal to prevent and effectively treat the 
disease by 2025. The way the math works out, if we could slow 
this disease down by 5 years out of those 15 pre-symptomatic 
years, we would cut Alzheimer's dementia in half, thus early 
stage biomarkers and early diagnosis toward early intervention 
are important priorities at our center and among our peer 
centers.
    To really transform medicine for this disease, we must also 
transform the way we think about it. For example, unless we 
counter the stigma that is attached to Alzheimer's Disease, 
neither patients nor primary care givers are likely to 
cooperate with an agenda for early diagnosis.
    At the University of Washington, we and our community 
partners have realized the importance of educating the public 
to understand the entire course of the disease, including its 
pre-symptomatic and mild cognitive impairment stages and the 
strengths a patient retains in the midst of it that become the 
basis for strength based interventions for persons with memory 
loss. Leading edge research really advances on this foundation 
of best care and community trust.
    To accelerate progress, exciting new approaches are 
emerging. One example in our Center is reprogramming skin 
biopsy cells to make patient specific disease models available 
in the laboratory coupled with more knowledge of genetics and 
especially new gene editing technology, this could illuminate 
the different molecular pathways that drive Alzheimer's disease 
in different patients leading us toward a genuine precision 
medicine for Alzheimer's disease.
    Better understanding of Alzheimer's disease ultimately 
requires more detailed data from each participant and 
aggregating that data nationally. Our field has a record of 
successful cooperation beginning with the NIH funded 
Alzheimer's Disease Centers Program that is operated for more 
than 30 years. I currently direct one of the Centers in this 
network that maintains subject registries and tissue 
repositories for Alzheimer's research and cross-institutional 
initiatives regularly leverage these resources. For example, 
the Alzheimer's Disease Neuroimaging Initiative, ADNI, has been 
pivotal to understanding early disease biomarkers and disease 
heterogeneity and has set a standard for data sharing and 
productivity.
    As another example, the dominantly inherited Alzheimer's 
Disease Network has assembled a nationwide cohort of people 
known to be genetically susceptible to amyloid driven 
Alzheimer's disease and is now conducting one of the first 
precision medicine treatment trials for which UW is one of the 
performance sites.
    We need more cooperation across NIH, industry, and 
charitable groups and new standards of data sharing. NIH 
funding is simply critical to all these efforts. It gives 
longevity to the research infrastructure, brings about 
standardization and thematic direction, enables cooperation at 
scale, trains new scientists, and ultimately is what will help 
us achieve the 2025 goal.
    The Alzheimer's Accountability Act passed in the 2015 
Omnibus Appropriations Bill authorized the NIH Director to 
analyze funding requirements beyond the NIH base budget to 
remain on track to achieve the goals of the National Plan. Dr. 
Collins has accordingly submitted a Professional Judgment 
Budget for fiscal year 2018 to Congress. I urge the whole 
committee to support it with enthusiasm and with optimism. With 
this support, we can defeat this disease.
    Thank you again for the opportunity to testify and I look 
forward to answering your questions.
    [The statement follows:]
          Prepared Statement of Thomas J. Grabowski, Jr., M.D.
    Good morning, Chairman Blunt, Ranking Member Murray (my Senator), 
and distinguished Members of the Subcommittee. Thank you for the 
opportunity to testify today about the value of medical research, which 
is something I do every day. It is an honor to appear before your today 
to provide my view of the pivotal role NIH funding plays in our efforts 
to counter Alzheimer's disease, one of the central challenges in 
biomedicine.
    My name is Thomas J. Grabowski, Jr. I am a neurologist at the 
University of Washington, where I direct our clinical and research 
Centers for Alzheimer Disease and other memory disorders, including the 
NIA-funded University of Washington Alzheimer Disease Research Center, 
and the UW Medicine Memory and Brain Wellness Center. My own research 
focuses on new brain imaging approaches in Alzheimer's disease and 
other degenerative diseases, using MRI imaging approaches.
Background
    Some 5 million Americans have Alzheimer's dementia, including one 
in nine people over age 65. It is the rare person whose circle has not 
been touched by this disease. Alzheimer's dementia in a person has an 
outsized impact, emotional and material, on an entire family. 
Alzheimer's is the only leading cause of death that can't be cured, 
prevented, or even slowed in 2017. Consequently, increasing numbers of 
persons are living with Alzheimer's dementia, and dying from it, and 
the numbers are set to more than double and even triple by 2050.
    If these facts aren't enough to call us to action, even larger 
numbers have latent pre-symptomatic disease. Alzheimer's dementia is a 
relatively late consequence of a disease process that has gone on in 
the brain for 15 years or more. The rate of outright dementia at age 65 
is less than 1 percent, but by age 65 fully 20 percent of persons, 
despite normal memory, already have moderate to severe levels of 
amyloid plaques in the brain, as has been demonstrated by spinal fluid 
tests or amyloid PET brain scans.
    Framing Alzheimer disease around its full course like this is 
critical to progress. The National Plan to Address Alzheimer's Disease 
has an overriding first goal to prevent and effectively treat 
Alzheimer's disease by 2025. The long pre-symptomatic phase is a window 
of opportunity for intervention. During this time period, different 
disease processes conspire to damage brain cells. Meanwhile positive 
lifestyle choices can postpone, literally by years, the tipping point 
at which the disease finally affects cognition. There is thus a clear 
opportunity for prevention of dementia by a combination of ``precision 
medicine,'' brain health programs, and early intervention. If we can 
slow the disease process down by 5 years (out of those 15 pre-
symptomatic years), we would cut Alzheimer's dementia in half. The 
search for a scalable imaging biomarker and early diagnosis and 
intervention are important priorities for our NIH-funded Alzheimer's 
Disease Research Center, and are goals shared by many of our peer 
Centers.
Toward Precision Medicine for Alzheimer's Disease
    AD often is co-morbid with related chronic illnesses such as 
microvascular brain injury and Lewy body disease (LBD). Moreover, 
genetic risk for AD now clearly highlights the potential for multiple 
molecular drivers and perhaps multiple pathogenic pathways. The vision 
of the University of Washington (UW) AD Research Center (ADRC) is to 
bring individual clarity to this enormous complexity--to achieve 
precision medicine for AD so that the right person is treated at the 
right time with the right prevention or therapeutic.
    Three key elements of precision medicine (Cholerton et al, 2016) 
are stratification by risk, detection of pathophysiological processes 
as early as possible (ideally before the disease manifests clinically), 
and alignment of mechanism of action of intervention(s) with an 
individual's molecular driver(s) of disease. Now gaining broad currency 
in cancer care, a precision medicine approach is beginning to be 
adapted to cognitive impairment and dementia.
    Under NIH funding, and the leadership of Drs. George Martin, Murray 
Raskind, Thomas Montine, and most recently myself, the UW ADRC has been 
helping to develop this approach to AD for 33 years. During its initial 
20 years, our Center focused on AD genetic risk. Although we continue 
these efforts, the nature of AD genetics research has evolved and now 
is accomplished within large consortia rather than a single Center 
Project. Ten years ago, UW ADRC made `Biomarkers and Experimental 
Therapeutics' our theme, recognizing that even the most sophisticated 
risk stratification will have limited impact without meaningful 
measures of preclinical disease and new therapeutics. The UW ADRC has 
been an incubator for development of recent national multicenter 
clinical trials, including the EXERT trial of aerobic exercise in 
Alzheimer disease (led by Dr. Laura Baker, now at Wake Forest 
University), a trial of Prazosin Treatment for Disruptive Agitation in 
Alzheimer's Disease (led by Drs. Elaine Peskind and Murray Raskind, 
UW), and the Study of Nasal Insulin to Fight Forgetfulness (SNIFF) led 
by Dr. Suzanna Craft, now at Wake Forest University.
    Our current research projects advance our theme by pursuing 
fundamental research on mechanisms of aging and their intersection with 
Alzheimer disease pathogenesis, innovative development of novel 
therapeutics through protein design, and dynamic functional 
connectivity fMRI as a new window into pathophysiologic processes of 
preclinical AD. Our Center has been designed to create the knowledge 
and tools needed to advance pre-clinical biomarkers, to lay the 
groundwork for novel experimental therapeutics, to collaborate 
substantively in multicenter clinical trials, and to reach out to 
underrepresented populations.
    UW ADRC vision and mission resonate strongly with the principles of 
the National Plan to Address Alzheimer's Disease. Ultimately, our 
efforts, combined with others, will drive optimally targeted and timed 
preventions and interventions for AD and related causes of dementia.
Overview of the University of Washington ADRC
    The structure of our NIA-funded Alzheimer's Disease Research Center 
includes five Core resources, including a Clinical Core that 
characterizes and follows hundreds of research subjects; three formal 
research projects; and a Satellite Core that reaches out to American 
Indian and Alaskan native populations.
    In research Project 1, ADRC Investigator Dr. Matthew Kaeberlein, 
also the Co-Director of the Nathan Shock Center on Basic Biology of 
Aging (funded by NIA), investigates the mechanisms by which two 
important and highly conserved signaling pathways involved in cellular 
aging determine cellular resistance to amyloid beta toxicity, using a 
roundworm animal model. The Project aims for fundamental insights into 
the conserved cellular responses to amyloid beta and the identification 
of new therapeutic targets in Alzheimer's disease.
    In Project 2, ADRC Investigator Dr. David Baker, also the Director 
of the UW Institute for Protein Design, is designing small molecules 
that bind specifically to different forms of amyloid beta (such as 
soluble monomers) using the Rosetta software suite for rational protein 
design, coupled with a distinctive crowdsourcing approach that his 
laboratory has used to great success in HIV and influenza. The idea is 
that rational protein design will enable evaluation of therapeutic 
approaches that target different hypotheses as to the precise mechanism 
of amyloid toxicity.
    In Project 3, ADRC Investigator Dr. Thomas Grabowski, also the 
Director of the UW Integrated Brain Imaging Center (which has received 
major funding from NINDS), is investigating new functional MRI imaging 
approaches for preclinical detection of Alzheimer disease. Functional 
connectivity fMRI (fcMRI) can map brain networks based on detecting 
synchronized activity across separate brain regions. In particular, the 
brains ``default network'' is systematically affected in early 
Alzheimer disease. In this project, fcMRI measures of default network 
integrity are being validated against CSF protein markers of 
Alzheimer's disease, extending our Alzheimer's Disease Research 
Center's work on preclinical biomarkers.
    Therapeutic Pipeline Project (TPP). In 2015 the Ellison Foundation 
made a $6 million gift to UW Medicine to foster the development of a 
``therapeutic pipeline'' for AD, based on precision medicine 
principles. This project leverages our Center's NIH-funded resources, 
and includes next-generation whole-exome sequencing to stratify trial-
ready subject groups, and the use of induced pluripotent stem cells to 
develop subject-specific neuron cultures that can be used as disease 
models to understand the different molecular pathways that drive 
Alzheimer disease in different individuals. We are turning to these 
tools to investigate Alzheimer disease mechanisms that include mTOR 
aging pathway, immune inflammatory responses by microglia, and 
endosomal trafficking of amyloid beta.
    Our Satellite Core is led by Dr. Dedra Buchwald of Washington State 
University, also the Director of Parterships for Native Health. Drawing 
on the vast experience of Dr. Buchwald's group in carrying out research 
in this unique, underserved, and complex population, the Satellite Core 
will follow 450 aging reservation-dwelling American Indians at three 
sites in Oklahoma, Arizona, and South Dakota for progression of 
cognitive impairment and imaging markers of neurodegenerative disease.
    Besides the Washington-based Centers mentioned above, the UW ADRC 
is closely partnered with the Adult Changes in Thought study, a 
longitudinal population-based prospective cohort study of brain aging 
and incident dementia in the Seattle metropolitan area, based at the 
Group Health Cooperative in Seattle, directed by Drs. Eric Larsen and 
Paul Crane, and continuously funded by the National Institute on Aging 
for 28 years.
On a Foundation of Care and Community Trust
    Our ADRC is partnered with the UW Medicine Memory and Brain 
Wellness Center clinic, a comprehensive multidisciplinary evaluation 
and treatment service for disorders affecting memory and cognition. Our 
combined mission is to promote the well-being of persons living with 
memory loss and their families, by providing exceptional care, 
advancing scientific understanding, and building dementia-friendly 
communities. The themes of the Memory and Brain Wellness Center clinic 
are early and accurate diagnosis, strengths-based reframing and 
treatment, and community transformation. Patients have access to state 
of the art genetic and imaging studies, integrated mental healthcare, 
cognitive rehabilitation, educational programming, and the option to 
participate in research via our patient Registry, through which they 
may connect to the ADRC, clinical trials, brain health studies, and 
others.
    For most people, even medical providers, ideas about Alzheimer 
disease are framed around dementia. To really transform medicine for 
Alzheimer's disease, we must also transform the way we (patients and 
families, physicians, and our society) think about the disease. For 
example, unless we counter the stigma attached to Alzheimer disease, 
neither patients nor primary care physicians are likely to cooperate 
with the important agenda of early detection. At the University of 
Washington, we and our community partners have realized the importance 
of educating the public to understand the entire course of Alzheimer 
disease, including its pre-symptomatic and mild cognitive impairment 
stages, and the strengths a person retains in the midst of it, as well 
as the importance of strengths-based programs for persons with memory 
loss.
    Our Washington State community partners include Momentia, a 
grassroots social movement in Seattle of persons living with early 
stage memory loss, transforming what it means to live with memory loss 
through empowerment and engagement in the community; the Western and 
Central Washington State Chapter of the Alzheimer's Association; the 
Dementia Action Collaborative implementing the Washington State Plan to 
Address Alzheimer's Disease; and other groups providing advocacy or 
engagement programming.
    We envision a world in which people live well with memory loss and 
can rely upon the best care, within a community of support. Leading-
edge research really advances on a foundation of best care and 
community trust.
Critical Importance of NIH Funding
    Progress in understanding of AD ultimately requires more detailed 
data from each research participant, and aggregating these data 
nationally. Our field has a record of successful large-scale 
cooperation, beginning with the Alzheimer's Disease Centers program of 
the National Institute on Aging that has operated for more than 30 
years. Ours is one such Center in this network, which forms the 
backbone, and maintains subject registries and tissue repositories for 
American AD research. Cross-institutional initiatives regularly 
leverage these resources. For example, the NIH-funded Alzheimer's 
Disease Sequencing Project (funded by NIA and the National Human Genome 
Research Institute) and Dominantly inherited Alzheimer Disease Network 
(DIAN, funded by NIA) make use of our resources. The Alzheimer Disease 
Neuroimaging Initiative has been pivotal to understanding early disease 
biomarkers and disease heterogeneity, and has set a standard for data 
sharing and productivity, continued and extended by other open 
neuroscientific initiatives from NIH (e.g. the Human Connectome 
Project) and charitable sources (e.g. the Allen Institute for Brain 
Science and Sage Bionetworks, both in Seattle). NIH- and industry-
sponsored treatment trials also make use of the resources of the 
Alzheimer Disease Centers. At our Center, these have included the DIAN 
Trials Unit, the Biogen EMERGE study of Aducanamab, and the Anti-
Amyloid in Asymptomatic Alzheimer's Disease (A4) study (funded by NIA 
and a public-private consortium).
    NIH funding is simply critical to all these efforts. It underlies 
most of the effort I have outlined in my testimony. NIH funding is what 
gives longevity to the research infrastructure, brings about 
standardization and thematic direction, enables cooperation at scale, 
trains new scientists, and ultimately will achieve the 2025 goal. We 
need to bring about even more cooperation across NIH, industry, and 
charitable groups; and new standards of data sharing to promote 
progress.
    The Alzheimer's Accountability Act authorized the NIH Director to 
analyze research funding requirements, beyond the NIH base budget, to 
remain on track to achieve the goals of the National Plan, with 
specific, targeted milestones Dr. Collins has submitted a Professional 
Judgment Budget for fiscal year 2018. I urge it on you with enthusiasm, 
and with optimism that we can defeat this disease.
Resources
    UW Medicine Memory and Brain Wellness Center: http://
www.depts.washington.
edu/MBWC.

    Living with Memory Loss: http://depts.washington.edu/mbwc/content/
page-files/LWML-Handbook_reduced_2_27_17.pdf.

    UW Alzheimer's Disease Research Center: http://
www.pathology.washington.edu/research/adrc.

    Momentia: http://www.momentiaseattle.org.

    Precision Medicine for Alzheimer's Disease: Cholerton B, Larson EB, 
Quinn JF, Zabetian CP, Mata IF, Keene CD, Flanagan M, Crane PK, 
Grabowski TJ, Montine KS, Montine TJ. Precision Medicine: Clarity for 
the Complexity of Dementia. Am J Pathol 186:500-6, 2016.

    Precision Medicine: Clarity for the Complexity of Dementia. [The 
article follows:]

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]

    Senator Blunt. Thank you, Dr. Grabowski. Dr. Schultz-
Cherry.
STATEMENT OF STACEY SCHULTZ-CHERRY, PHD, MEMBER, 
            DEPARTMENT OF INFECTIOUS DISEASES, ST. JUDE 
            CHILDREN'S RESEARCH HOSPITAL, MEMPHIS, 
            TENNESSEE
    Dr. Schultz-Cherry. Yes. Chairman Blunt, Ranking Member 
Murray, and distinguished subcommittee members, thank you for 
inviting me to share my perspective on ``Saving Lives Through 
Medical Research.''
    As you may know, St. Jude's mission is to advance cures and 
means of prevention for pediatric and catastrophic diseases 
through research and treatment. Since St. Jude opened its doors 
in 1962, no child is denied its treatment based on race, 
religion, or a family's ability to pay.
    What you may not know is that St. Jude has also been on the 
forefront of the ongoing battle with pandemic influenza as well 
as other emerging viruses. In addition to my faculty position, 
I serve as the Deputy Director of the World Health Organization 
Collaborating Center for Influenza that is based at St. Jude. 
We focus solely on threats to humans from animal viruses and we 
work closely with WHO (World Health Organization) centers 
around the world to guide both research and response. We also 
produce and distribute materials for vaccines to use against 
emerging viruses.
    Today, what I would really like to focus on is how critical 
it is to have adequate funding for infectious diseases really 
focused on four main points: threat, competition, preparation, 
and discovery. Zika, Ebola, antibiotic-resistant bacteria, 
influenza, even measles and mumps have highlighted how 
important infectious disease research is.
    Since 1980, approximately one to three new human infections 
have been identified each year, either emerging or reemerging, 
many from animal sources. And while many of these were 
originally thought to be problems of the developing world, 
Ebola and Zika highlights that these viruses and these microbes 
have no boundaries.
    The cost of these outbreaks is staggering, both in terms of 
economics and the impact on human health. Take for example 
Zika. It's really called the epidemic of delay. We know the 
impact of babies born to infected mothers or people developing 
Guillian-Barre syndrome, but what's actually going to happen 10 
years from now from people that have been infected and perhaps 
didn't realize that they were? We really have no idea and this 
remains to be seen and researched.
    Further, we have diseases in our own backyard considered 
neglected diseases of poverty that happen all throughout the 
Southern United States. This is not the developing world. This 
is in our own backyard and we need to better research this 
threat.
    So how do we prepare for these continued threats? Stable 
funding from the NIH is key to building relationships with 
researchers within the U.S. as well as outside the U.S., 
especially in areas considered high risk. And we know from our 
work at St. Judge that this actually works.
    So in the late 1990s St. Jude was awarded a contract from 
the National Institutes of Health to study influenza viruses 
across the world. We have built partnerships throughout many 
parts of the world, including Southeast Asia. And while we were 
studying influenza virus, what actually happened is we--our 
partners ended up discovering, isolating, and identifying, the 
causative virus of SARS.
    Because of the success of these contracts, we now have a 
network of Centers of Excellence for Influenza Research 
throughout the U.S. that is doing research, training people in 
infectious diseases, and they're now at the forefront of both 
influenza as well as emerging infectious diseases. The Center 
for Excellence researchers have actually also been involved in 
MERS and now Zika virus. It also allows us to provide critical 
information to the World Health Organization and the CDC to 
support global public health.
    And really if you have questions whether these threats are 
real, in the past 3 days we've seen an outbreak of highly 
pathogenic avian influenza virus in poultry in Tennessee and 
now one in Wisconsin.
    Competition. The U.S. has long been a leader in the 
biomedical research world. Unfortunately, we are seeing a 
disturbing trend in the number of patents being awarded to U.S. 
researchers as well as even submissions of publications to 
papers. One of the leading infectious disease journals found a 
disturbing trend that from 2010, 75 percent of--actually, 60 
percent of submissions were from U.S. based scientists dropping 
to 37 percent in 2015. While there are many reasons for this, 
it is something that requires careful analysis.
    Part of the preparation is training our next generation of 
scientists. And this is something I take very seriously, 
especially as my incoming role of the President of the American 
Society for Virology. There's a disturbing trend that many of 
our trainees do not want to pursue academic research. And one 
of the reasons is they're concerned about funding because they 
know funding equals success. In fact, one of my own trainees 
who is outstanding has taken a position in Cambodia because 
he's afraid of this.
    And finally, it is discovery. Without basic research, we 
are not going to find the universal flu vaccine or new 
antibiotics, and so this is crucial for the future of the U.S.
    [The statement follows:]
            Prepared Statement of Dr. Stacey Schultz-Cherry
    Chairman Blunt, Ranking Member Murray, and distinguished 
Subcommittee Members, thank you for inviting me to share my perspective 
on ``Saving Lives through Medical Research.'' My name is Dr. Stacey 
Schultz-Cherry, and I am a member of the faculty in the Department of 
Infectious Diseases at St. Jude Children's Research Hospital in 
Memphis, Tennessee. As you may know, St. Jude's mission is to advance 
cures and means of prevention for pediatric catastrophic diseases 
through research and treatment. Since St. Jude opened its doors in 
1962, no child is denied treatment based on race, religion or a 
family's ability to pay.
    St. Jude also is at the forefront of the ongoing battle against 
pandemic influenza as well as other emerging viruses. In addition to my 
faculty position, I serve as the Deputy Director of the World Health 
Organization (WHO) Collaborating Center for Influenza at St. Jude, 
which is focused exclusively on the threat to humans from influenza 
viruses that emerge from animals. We work closely with other WHO 
centers around the world to guide global influenza research and 
response. St. Jude produces and distributes materials for vaccines for 
use against emerging viruses, including pandemic threats.
    As an institution, St. Jude is grateful for the wonderful 
relationships we have with so many Members of this Subcommittee and 
your staffs, and we welcome all of you to visit us in Memphis to see 
what a difference our work makes in the lives of the children around 
the globe.
    Today I would like to talk about how critical it is to have 
adequate funding for medical research and the consequences of 
insufficient support for basic research on infectious diseases. Federal 
support for medical research is critical to be prepared for the threat 
of emerging and reemerging diseases, to secure the United States' 
position as a global leader in medical research, to ensure that as a 
country we are able to attract and retain the brightest minds to 
medical research, and to continue to create the conditions under which 
ground-breaking medical discoveries are made. I will address each of 
these in turn.
Threat: Ongoing Threats Posed by Emerging and Reemerging Diseases
    Zika, Ebola, antibiotic-resistant bacteria, Chagas, SARS and MERS, 
influenza viruses, even measles and mumps: these are just a few 
examples of the recent threats we have faced from emerging and re-
emerging infectious diseases. Since 1980, approximately one to three 
new human infectious diseases have been identified each year; others 
have ``re-emerged,'' causing greater numbers of cases than before and/
or affecting different populations and regions than in the past.\1\ 
According to the Centers for Disease Control and Prevention (CDC), 
greater than 60 percent of all known infectious diseases in people are 
spread from animals and 75 percent of the new or emerging infectious 
diseases in people have an animal source.
---------------------------------------------------------------------------
    \1\ Jones, K. E. et al. Global trends in emerging infectious 
diseases. Nature 451, 990-993, doi:10.1038/nature06536 (2008).
---------------------------------------------------------------------------
    While many of these infections historically have been problems of 
the developing world, the recent Ebola and ongoing Zika outbreaks in 
the United States highlight that infectious diseases know no 
boundaries. During the Munich Security Conference in February 2017, 
Bill Gates was quoted as saying ``Whether it occurs by a quirk of 
nature or at the hand of a terrorist, epidemiologists say a fast-moving 
airborne pathogen could kill more than 30 million people in less than a 
year. And they say there is a reasonable probability the world will 
experience such an outbreak in the next 10 to 15 years.''
    The cost of these outbreaks is staggering. Estimates of the 
economic cost of an influenza pandemic range from $374 billion (in 2014 
US dollars) for a mild pandemic to $7.3 trillion for a severe pandemic 
with 12.6 percent loss of gross domestic product (GDP).\2\ The cost to 
human life could be even greater. Take for example Zika virus, which 
has been called an ``epidemic on delay.'' The impact on babies born to 
infected mothers or people developing Guillian-Barre syndrome after 
infection are well-appreciated, but the long-term effects of the 
epidemic are unknown. Whether infection results in future health 
effects or long term neurological deficits in infected people of all 
ages remains to be seen.
---------------------------------------------------------------------------
    \2\ Pike, J., Bogich, T., Elwood, S., Finnoff, D. C. & Daszak, P. 
Economic optimization of a global strategy to address the pandemic 
threat. Proceedings of the National Academy of Sciences of the United 
States of America 111, 18519-18523, doi:10.1073/pnas.1412661112 (2014).
---------------------------------------------------------------------------
    Further, there is a burden of disease caused by a group of 
infections typically only seen in the developing world that is largely 
hidden and that is known as the neglected infections of poverty. These 
diseases occur primarily in the Mississippi Delta and elsewhere in the 
Southern United States, as well as in disadvantaged urban areas and 
peoples living in Appalachia.\3\ In several of these areas, many of the 
diseases we are most concerned about such as Zika, dengue, and diseases 
of animals that can transmit to humans (for example rabies), not only 
occur but thrive and could be a source for a widespread disease threat.
---------------------------------------------------------------------------
    \3\ Hotez, P. J. Reinventing Guantanamo: from detainee facility to 
Center for Research on Neglected Diseases of Poverty in the Americas. 
PLoS neglected tropical diseases 2, e201, doi:10.1371/
journal.pntd.0000201 (2008).
---------------------------------------------------------------------------
    How do we prepare for these continued threats? Stable funding for 
the National Institutes of Health (NIH) to build relationships and 
capacity with partners across the United States, especially in these 
areas considered ``high risk'', and around the world is key not just to 
preparing for but possibly predicting the next emerging/reemerging 
infectious disease threats. These monies must go beyond the basic 
research, and must include research and surveillance at the animal-
human interface, which is the source of most emerging infectious 
diseases.
    We know from our own work at St. Jude Children's Research Hospital 
that this approach works. The 1997 outbreak of highly pathogenic H5N1 
avian influenza in humans in Hong Kong highlighted the need for global 
influenza surveillance to protect human health. In response, in 1999, 
the National Institute for Allergy and Infectious Diseases (NIAID) 
awarded a contract to St. Jude to set up continuous surveillance of 
aquatic birds and live bird markets in Hong Kong in collaboration with 
partners in Hong Kong, Southeast Asia, and the United States. In 
addition to this early warning system, this contract provided training 
and capacity building in this region of the world and fed invaluable 
information and reagents into the WHO and CDC influenza response 
systems. Ultimately, this program developed a candidate seed vaccine 
strain. An unexpected second benefit of this program was the detection 
and characterization of the causative virus of SARS in 2003 by one of 
our Hong Kong collaborators, Dr. Malik Peiris.
    Given the success of the initial contract awarded to St. Jude, 
NIAID established the Centers for Excellence in Influenza Research and 
Surveillance (CEIRS) network. The first 7 year contract, which funded 
five centers, resulted in the expansion of animal influenza 
surveillance programs internationally and domestically and focused on 
several high priority areas in influenza research. These projects 
provided key information on influenza virus-induced disease and 
immunity, assisted in the development of the Influenza Research 
Database, (an NIAID-funded program that provides datasets and 
bioinformatics tools to the global research community), and made 
important contributions to influenza reagent developments and data 
sharing. Equally important were the training and lab capacity-building 
activities the Centers supported within the U.S. and around the world. 
These activities enhance influenza research and response, and build 
infrastructure that can be applied to other infectious diseases. 
Arguably, some of the most important activities under the 2007-2014 
contracts were a response to the 2009 H1N1 pandemic, in which the CEIRS 
network was instrumental in conducting early virus characterization 
studies and pre-clinical evaluation of vaccine material.
    We are now in our second generation of the CEIRS network contracts. 
While the focus remains on influenza viruses, we have seen the 
emergence of MERS and Zika viruses. The response capabilities and 
collaborations established with partners within the U.S. and around the 
world have made it possible for the CEIRS network to rapidly respond to 
any emerging threat. CEIRS scientists again were among the first to 
identify and characterize the virus that causes MERS, determine that 
camels were a key source for human infections, and continue to ``look 
for'' MERS in animal and humans around the world. The new capabilities 
conferred through CEIRS also allowed us to respond to Zika rapidly. 
Given our long-term CEIRS-funded studies in Colombia, South America, 
NIH was able to establish Zika studies quickly in an area with an 
emerging Zika epidemic. However, our studies go beyond Zika infection. 
We want to understand what happens to a pregnant woman and her child 
when she gets co-infected with influenza virus and Zika, dengue or even 
chikungunya virus, a real threat to pregnant women throughout the 
Americas, especially in an influenza epidemic year like we are facing 
currently. These critical studies for human health would be impossible 
without sustained NIH funding.
    If there were any doubt that these threats are real and can strike 
at any time, the USDA APHIS confirmed on Monday that highly pathogenic 
avian H7 influenza virus was identified in a commercial breeder flock 
in Lincoln County, Tennessee. The source of the virus appears to be 
wild birds. The threat to humans is currently unknown.
Competition: The U.S. as a Global Leader in Medical Research
    The U.S. long had been the leader in biomedical research. 
Unfortunately, this trend is changing. A recent publication by Moses, 
et al. in the Journal of the American Medical Association (JAMA) used 
publicly available data from 1994 to 2012 to show that the decrease in 
US funding for biomedical research correlated with a decrease in the 
U.S. share of life sciences patents, with those considered most 
valuable decreasing from 73 percent in 1981 to 59 percent in 2011.\4\
---------------------------------------------------------------------------
    \4\ Moses, H., 3rd et al. The anatomy of medical research: US and 
international comparisons. Jama 313, 174-189, doi:10.1001/
jama.2014.15939 (2015).
---------------------------------------------------------------------------
    This is also evident when reviewing publications from U.S. and 
foreign investigators. In 2009, the U.S. led the world in research 
productivity, with 33 percent of published biomedical research articles 
and numbers of articles from U.S. investigators increasing at 0.6 
percent per year from 2000 to 2009. We also led the world in the 
numbers of most highly cited biomedical research articles with 63 
percent of the top cited articles in 2000 and 56 percent in 2010. Yet, 
during the same period, the number of articles published in China 
increased by 18.7 percent annually and the number of highly cited 
literature from China continued to increase. After controlling for the 
share of the world's biomedical research articles using a citation 
index, publications from the U.S. declined -0.2 percent from 2000 to 
2010 per year as the rest of the world increased by approximately 1 
percent per year.\4\ The trend is even more concerning when considering 
the number of biomedical research articles submitted to major 
infectious disease journals.

[GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]


    Figure 1 illustrates the trends from four major infectious disease 
journals from 2010 through 2016. Overall, the number of submissions 
from foreign investigators has continued to increase as compared to 
those from U.S.-based scientists, but there are a few trends. In one 
journal, U.S.-based submissions were consistently lower than those 
received from foreign investigators (Figure 1B). However, most journals 
showed progressive decreases in submissions from US-based 
investigators. Figure 1C highlights a dramatic shift in one journal; 
where in 2010 60 percent of submissions were from U.S.-based scientists 
dropping to 37 percent in 2015. In all cases, the majority of foreign-
based submissions come from China.
    There are different explanations for these changes, and 
understanding journal trends and US competitiveness in scientific 
research will require careful analysis.
Preparation: Encouraging the Next Generation of Medical Researchers
    A key to fighting infectious disease threats is training the next 
generation of scientists, including the physician-scientists and Doctor 
of Veterinary Medicine-scientists that likely will be at the frontline 
of the fight. One of the highlights of my career has been mentoring the 
next generation of scientists. It is something that I take seriously 
and will be a major focus during my term as the President of the 
American Society for Virology. Yet over the past 5 years, we have seen 
a disturbing trend: increased numbers of trainees do not want to pursue 
faculty positions in an academic setting. A recent study by the 
University of California at San Francisco (UCSF), a world renowned 
biomedical research institution, tracking their trainees' careers 
showed that only 37 percent of U.S.-employed postdoctoral alumni were 
in faculty positions, which included non-tenure track faculty-like full 
time research or teaching positions with the majority of these employed 
at research institutions. The outcome is very different for UCSF 
postdoctoral alumni that left the U.S. In that case, 54percent were in 
faculty positions.\5\
---------------------------------------------------------------------------
    \5\ Silva, E. A., Des Jarlais, C., Lindstaedt, B., Rotman, E. & 
Watkins, E. S. Tracking Career Outcomes for Postdoctoral Scholars: A 
Call to Action. PLoS biology 14, e1002458, doi:10.1371/
journal.pbio.1002458 (2016).
---------------------------------------------------------------------------
    When I ask a trainee why he or she does not want to pursue a career 
in academic research, not receiving NIH funding is a primary concern. 
Trainees know that the lack of funding will make it difficult to be 
productive and ultimately obtain tenure. The low NIH payline 
(determined by the score you receive during the peer review process) 
also requires that young investigators spend more time writing grants 
rather that performing research.\6,7\ Stability of funding may be even 
more important for the careers of young scientists than the overall 
size of the Department of Health and Human Services or NIH. Boom-and-
bust cycles wipe out generations of young scientists and discourage 
people from taking a chance in research careers. This means that only 
older scientists stay in the game. In 2011, the average age of first-
time R01 grantees was 42 for Ph.D.s and mid-to-late 40s for M.D. and 
M.D.-Ph.D. scientists. It is likely even higher now. We also are seeing 
a skewing in the age of NIH-funded Principal Investigators (PIs). In 
the 1980s the majority were 35 and younger with less than 1 percent 
over age 66. Since the 2000's this has reversed, with the majority of 
NIH PIs now older than 66.
---------------------------------------------------------------------------
    \6\ Daniels, R. J. A generation at risk: young investigators and 
the future of the biomedical workforce. Proceedings of the National 
Academy of Sciences of the United States of America 112, 313-318, 
doi:10.1073/pnas.1418761112 (2015).
    \7\ Powell, K. Young, talented and fed-up: scientists tell their 
stories. Nature 538, 446-449, doi:10.1038/538446a (2016).
---------------------------------------------------------------------------
    In many cases, young investigators are required to have funding 
before they even can apply for faculty positions, making it difficult 
if not impossible for many to find their first ``real job.'' ``Erik'' 
is an example of this. He came to my laboratory as a postdoctoral 
fellow to study the impact of obesity on influenza infection and 
vaccination response, after receiving his Ph.D. in nutrition from the 
University of North Carolina at Chapel Hill. This is a very creative, 
ambitious and productive young scientist at the interface of nutrition 
and infectious diseases. In spite of an outstanding CV, he was having 
difficulties finding a faculty position because he did not already have 
independent NIH funding. Many departments were concerned that it could 
be difficult for him to obtain funding for his work, despite the 
cutting edge research he was doing. Instead of staying in the U.S., 
Erik has decided to accept a position as the Head of Virology at one of 
the Institute-Pasteur laboratories. While I am excited to see him begin 
his independent career and know that he will be successful, it is 
discouraging that he has to leave the U.S. to pursue his dreams to be a 
PI.
    It is not only the careers of young investigators that are of 
concern, but those of the mid-level PIs like me. In many cases, we are 
the ``workhorses'' of our fields, serving as journal editors, NIH study 
section members, teachers for undergraduate, graduate, medical, and 
professional students, heads of admissions committees, even becoming 
Presidents of our respective societies. Yet unlike our more junior 
colleagues, we are ``too old'' to apply for many of the funding 
opportunities specific for young investigators, and may not have the 
``name recognition'' of our more senior colleagues. While on the 
faculty at the University of Wisconsin-Madison, several of my 
colleagues at the Associate Professor-level and even Professor-level 
had to close their research laboratories due to a lack of funding. 
While they were able to provide other invaluable contributions to the 
department and university it was a significant loss to basic research. 
In summary, not only are we failing to bring young people into 
infectious disease research, but we also are losing many of our 
``soldiers'' in the fight. This will leave us ill-prepared to face 
future threats, which we know will continue.
Discovery: Basic Research is the Foundation for Important Medical 
        Discoveries
    Federal funding for basic research is an important foundation of 
societal progress, sustainability, economy and obviously the health and 
well-being of the population.\8\ Without funding for basic research and 
especially funding for high-risk, innovative research, we will never 
develop a universal influenza vaccine, new antibiotics to combat 
antibiotic resistant microbes, or crucial new cancer therapies. In 
terms of infectious disease research, in order to be at the forefront 
of the next threat, we need to understand what is happening in our 
animal populations (domestic and wildlife), and appreciate that our 
population is aging and expanding, which can impact infectious disease 
emergence, transmission, disease severity and even efficacy of our 
therapeutic strategies.
---------------------------------------------------------------------------
    \8\ Murray, D. L. et al. Bias in Research Grant Evaluation Has Dire 
Consequences for Small Universities. PloS one 11, e0155876, 
doi:10.1371/journal.pone.0155876 (2016).
---------------------------------------------------------------------------
    Over the weekend, a global electronic reporting system for 
outbreaks of emerging infectious diseases and toxins called ``ProMED-
mail'' posted notifications on new meningococcal meningitis, measles 
and mumps outbreaks on college campuses across the US; the continued 
westward spread of highly pathogenic avian H5 influenza virus; four new 
human cases of avian H7N9 influenza infection in humans; and an 
outbreak of an undiagnosed respiratory disease in Hong Kong, all 
highlighting the ongoing threat posed by infectious diseases. The next 
Jonas Salk, George Washington Carver, Marie Curie, or Jane Goodall may 
be working in our laboratories. Let's not lose any of them.
                                * * * *
    I extend my sincere appreciation to the Subcommittee for asking me 
to share my views with you today, and I look forward to answering any 
questions you have.

    Senator Blunt. Thank you, Dr. Schultz-Cherry. Dr. Sasser.
STATEMENT OF JENNIFER SASSER, PHD, ASSISTANT PROFESSOR, 
            UNIVERSITY OF MISSISSIPPI MEDICAL CENTER, 
            JACKSON, MISSISSIPPI
    Dr. Sasser. Chairman Cochran, Chairman Blunt, Vice Chairman 
Leahy, and Ranking Member Murray, and members of the 
subcommittee, thank you for the opportunity to appear before 
the subcommittee today. I am Jennifer Sasser, an Assistant 
Professor in the Departments of Pharmacology and Physiology at 
the University of Mississippi Medical Center.
    I would like to thank the committee for its steadfast 
support of the National Institutes of Health and for medical 
research in general. The funding provided by Congress ensures 
that the body of knowledge for both discovery and translational 
research applications continues to grow to the benefit of all 
Americans. This steady support is critical to my future, the 
future of my students and research assistants, and most 
importantly, to the countless people who will receive better 
care due to the work funded by NIH.
    My research mission is to better understand and treat 
preeclampsia, a disease of high blood pressure during 
pregnancy. Preeclampsia endangers mothers during pregnancy and 
increases their risk of later heart attacks, strokes, and 
kidney disease. In addition, this disease puts the lives and 
futures of newborns at risk from the very start with the 
resulting births costing Mississippi $330 million a year. 
Identifying better treatments for preeclampsia and reducing 
pre-term birth will have a direct impact on the health of 
mothers and children in Mississippi and nationwide while 
reducing the cost to treat them.
    Being an early career researcher today comes with a unique 
set of challenges. The pressure to win grants is palpable and 
the competition for funding is stronger than ever. This 
competitive environment leads to few awards, most of which are 
won by seasoned veterans at select institutions making it hard 
for young investigators to get a toehold in the research world.
    The Institutional Development Award, or IDeA program, has 
provided critical support to Mississippi researchers for years 
funding a number of groundbreaking projects across the State. 
This program allows us to compete on a more level playing field 
increasing our ability to secure funding. Thanks to IDeA 
support, my research program is now competing successfully with 
top programs in the country.
    At the end of last year, an editorial in ASBMB Today 
entitled ``Send My Tax Dollars to Mississippi'' stated that 
taxpayers net more scientific publications by funding 
investigators at the University of Mississippi Medical Center 
than by giving the funds to prestigious and top ranked 
institutions. This article underscores what I have learned 
firsthand, that the IDeA program is a good investment, 
benefitting taxpayers, the research community, and the 
recipient States.
    The pressure to secure grants compounded by low funding 
rates can often by a career ender for talented and highly 
trained young investigators. As the Director of our graduate 
program in Medical Pharmacology, this is a dilemma that I and 
others face every year when we decide which students we can 
accept into our PhD program. How can we responsibly train 
students for careers that may not be sustainable in the future? 
How many students should we take when the number of positions 
after graduation is decreasing?
    Of course, we emphasize the many career paths available to 
biomedical PhD graduates, but we have to balance our enthusiasm 
for training the next generation of biomedical researchers with 
the harsh realities of highly competitive funding, fewer 
academic positions, and reductions in workforce in 
pharmaceutical and biotechnology industries.
    I am fortunate to have benefitted not only from 
Mississippi's IDeA State status, but also from vital assistance 
from the NHLBI (National Heart, Lung, and Blood Institute) and 
the NIDDK (National Institute of Diabetes and Digestive and 
Kidney). As a postdoctoral fellow, my stipend was supported by 
an Institutional Training Grant from the NHLBI, which allowed 
me the time to develop the skills necessary for this career 
path. I then successfully competed for a career development 
award from the NIDDK which allowed me to fully establish myself 
as an independent scientist. These training and career 
development programs are essential for continuing our pipeline 
of scientists in the coming generations. And I credit these 
programs for kick-starting my career and giving me the 
stability and confidence to pursue a lifetime in biomedical 
research.
    In January, I received the notice of award for my first R01 
grant, the gold standard grant mechanism. I would not have 
reached this goal so quickly without the commitment of the 
NHLBI to early stage investigators. This additional support is 
critical to young researchers who face tenure deadlines and may 
be denied the opportunity to continue their careers if they do 
not meet this R01 milestone. Without NIH support, many labs are 
forced to downsize or completely shut down, forfeiting years of 
investment in that researcher's training, as well as training 
positions for fellows, students, and employment opportunities.
    With this R01 award, I will grow my laboratory to support 
additional PhD students and research assistants, increasing the 
number of trainees as well as high quality jobs in the State.
    On behalf of many young researchers, I urge you to continue 
to provide funds for early career programs like these and 
encourage NIH to explore how other agencies might enhance their 
programs to support fledgling investigators.
    Thank you for the opportunity to appear before the 
committee and I am happy to answer any questions.
    [The statement follows:]
            Prepared Statement of Jennifer M. Sasser, Ph.D.
    Chairman Cochran, Chairman Blunt, Vice Chairman Leahy and Ranking 
Member Murray, thank you for the opportunity to appear before the 
Subcommittee today. I am Jennifer Sasser, an Assistant Professor in the 
Departments of Pharmacology and Physiology at the University of 
Mississippi Medical Center.
    I would like to thank the Committee for its steadfast support for 
the National Institutes of Health and for medical research in general. 
The funding provided by Congress ensures that the body of knowledge for 
both discovery and translational clinical applications continues to 
grow to the benefit of all Americans. This steady support is critical 
to my future, the future of my students and research assistants and, 
most importantly, to countless people who will receive better care due 
to the work funded by NIH.
    My research mission is to better understand and treat preeclampsia, 
a disease of high blood pressure during pregnancy. Preeclampsia 
endangers mothers during pregnancy and increases their later risk of 
heart attacks, stroke and kidney disease. In addition, this disease (I 
omitted the word ALSO here) puts the lives and futures of newborns at 
risk from the very start, with the resulting preterm births costing 
Mississippi $330 million a year. Identifying better treatments for 
preeclampsia and reducing pre-term birth will have a direct impact on 
the health of mothers and babies in Mississippi and nationwide, while 
reducing the cost to treat them.
    Being an early career researcher today comes with a unique set of 
challenges. The pressure to win grants is palpable, and the competition 
for funding is stronger than ever. This competitive environment leads 
to few awards, most of which are won by seasoned veterans at select 
institutions, making it hard for young investigators to get a toehold 
in the research world. The Institutional Development Award, or IDeA, 
program has provided critical support to Mississippi researchers for 
years, funding a number of groundbreaking projects across the State. 
This program allows us to compete on a more level playing field, 
increasing our ability to secure funding. Thanks to IDeA support, my 
research program is competing successfully with top programs in the 
country.
    At the end of last year, an editorial in ASBMB Today entitled 
``Send My Tax Dollars to Mississippi'' stated that ``taxpayers net more 
scientific publications by funding investigators at the University of 
Mississippi Medical Center ... than by giving the funds to prestigious 
and top-ranked institutions.'' This article underscores what I've 
learned firsthand--that the IDeA program is a good investment, 
benefiting the taxpayers, the research community and the recipient 
States.
    The pressure to secure grants, compounded by low funding rates, can 
often be a career ender for talented and highly trained young 
researchers. As the Director of our graduate program in Medical 
Pharmacology, this is a dilemma I and others face every year when 
deciding which students we can accept into our PhD program. How can we 
responsibly train students for careers that may not be sustainable in 
the future? How many should we take when the number of positions 
available after graduation is decreasing? Of course, we emphasize the 
many career paths available to biomedical PhD graduates, but we have to 
balance our enthusiasm for training the next generation of scientists 
with the harsh realities of highly competitive funding, fewer academic 
positions, and reductions in workforce in the pharmaceutical and 
biotechnology industries.
    I am fortunate to have benefitted not only from Mississippi's IDeA 
state status, but also from vital assistance from the NHLBI and the 
NIDDK. As a postdoctoral fellow, my stipend was supported by an 
Institutional Training Grant from the NHLBI, which allowed me time to 
develop the skills needed for this career path. I then successfully 
competed for a career development award from the NIDDK which allowed me 
to fully establish myself as an independent scientist. These training 
and career development programs are essential for continuing our 
pipeline of scientists in the coming generations, and I credit these 
programs for kick-starting my career and giving me the stability and 
confidence to pursue a lifetime of work in medical research.
    In January, I received a notice of award for my first R01 grant, 
the ``gold standard'' grant mechanism. I would not have reached this 
goal so quickly without the commitment of the NHLBI to Early Stage 
Investigators. This additional support is critical to young researchers 
who face tenure deadlines and may be denied the opportunity to continue 
their careers if they do not meet the R01 milestone. Without NIH 
support, many labs are forced to downsize or shut down, forfeiting 
years of investment as well as training positions for fellows and 
students and employment opportunities. With this R01 award, I will grow 
my laboratory to support additional PhD students and research 
assistants, increasing the number of trainees and high-quality jobs in 
the State. On behalf of the thousands of young researchers just getting 
their start, I urge you to continue to provide funds for early career 
programs like these and to encourage NIH to explore how other agencies 
might enhance their programs to support fledgling investigators.
    I thank you for the opportunity to appear before the Committee 
today and am happy to answer any questions you may have.

    Senator Blunt. Thank you, Dr. Sasser.
    Of course, we are pleased to have the Ranking Member of the 
Committee with us as well, not to mention the president pro tem 
emeritus of the Senate. So, Senator Leahy, if you'd like to 
make a comment this would be a good time.

                 STATEMENT OF SENATOR PATRICK J. LEAHY

    Senator Leahy. Thank you, Mr. Chairman.
    I do thank you and Senator Murray for having this hearing. 
I think the medical research is one of the most vital things in 
our country. We have imminent scholars and speaking here and I 
would also mention in the University of Vermont medical 
researching funding opportunities are critical, and not only 
because of the research we do there, but the people it attracts 
there.
    This commitment of what we've done this subcommittee has 
resolved billions of dollars of increase for NIH or the past 
year fiscal years, including the billions promised or the 
Twenty-First Center Cures Fill.
    But I worry when we say, ``Well, we've got to take money 
for things.'' $25 billion for a wall or the Mexican border 
which will have to come from somewhere in here, a huge increase 
in defense spending. I would urge all Senators, you can't hit a 
pause button on research. And, Dr. Grabowski, you talked about 
Alzheimer's. You can't say, ``Oh, well, just stop the research 
for a few years and come back to it.'' Just, you can't in 
cancer or any other areas.
    And so I think in the Appropriations Committee we can talk 
about our national priorities frankly. I think the big national 
priority is medical research. There is no family that doesn't 
know somebody or have a member of the family who has suffered 
from cancer or heart conditions, diabetes, even Alzheimer's. I 
can't imagine any American who thinks that we should cut back 
on research in they might say in the most powerful wealthiest 
nation on earth, why aren't we doing more?
    So I'll put my whole statement in the record, Mr. Chairman, 
and I thank you.
    [The statement follows:]
             Prepared Statement of Senator Patrick J. Leahy
    I want to thank Chairman Blunt and Ranking Member Murray for 
holding this important hearing to discuss the importance of medical 
research in saving lives.
    Medical research holds tremendous promise and is responsible for 
breakthroughs with diseases like cancer and Alzheimer's. Federal 
research dollars provide the Nation's top professions with the 
resources they need to continue expanding medical knowledge. The 
tireless devotion of researchers to finding cures has served as a 
catalyst for nationwide medical advancement.
    At the University of Vermont, medical research funding 
opportunities are critical, not just for creating new medical 
advancements but for attracting the best faculty members and 
researchers to Vermont. Last year, research funding through NIH 
accounted for nearly $40 million at UVM, supporting hundreds of jobs 
and students. Research through the University has led to advancements 
in lung disease treatment, cancers, and more effectively using genome 
testing to advance precision medicine. I was proud to host Vice 
President Biden at the University of Vermont to discuss his Cancer 
Moonshot initiative and how Vermont is contributing to research to 
better treat--and hopefully cure--the disease.
    This subcommittee has recognized the importance of funding medical 
research. This commitment has resulted in billions of dollars in 
increases for NIH over the last few fiscal years in addition to the 
billions of dollars promised with the passage of the 21st Century Cures 
bill in December.
    Unfortunately, the progress we have made is in jeopardy as medical 
research funding and so many other programs are in the crosshairs for 
fiscal year 2018. Medical research cannot be turned on and off. 
Scientists don't hit ``pause'' on studies and continue the research 
when Federal funding resumes. The ups and downs of the budget are 
particularly harmful in the medical research field. Budding scientists 
and researchers might decide to seek other career paths, leaving fewer 
scientists and therefore, fewer scientific discoveries. We must prove 
to the world that we will stand firm on our commitment to medical 
research for generations to come.
    President Trump has proposed a different approach. He wants to make 
deep cuts to domestic programs to pay for increased defense spending 
and to build a misguided and expensive wall on our southern border. 
President Trump seeks to implement this unbalanced agenda at the 
expense of other priorities that will affect all of us, especially when 
it comes to medical research. This is not only misguided policy, it 
flies in the face of the Budget Agreement which is meant to ensure 
parity between defense and non-defense spending.
    The Appropriations Committee is where our national priorities are 
translated into reality. I look forward to working with this 
subcommittee and others to ensure that cuts are not made that would 
undermine our progress on medical research. I look forward to hearing 
from our witnesses today on the importance of medical research and how 
Federal contributions are critical.
    Thank you, Chairman Blunt, for holding today's hearing.

    Senator Blunt. Thank you, Senator. We'll have a five-minute 
round of questions. And Senator Murray--I'll start and then 
recognize you.

                           PRECISION MEDICINE

    Dr. Eberlein, you mentioned in treating breast cancer that 
the normal treatment would usually include surgery, then 
radiation, then chemotherapy. And you also said that your 
estimates would be that four out of five patients wouldn't need 
both radiation and chemotherapy. How do you determine that? 
What are you doing to try to help determine which four patients 
don't have to, one, pay for it, but more importantly go through 
the personal effort of having a treatment that they don't need? 
How do we know which ones would need it or how do you hope we 
figure out which patients need it and which patients don't?
    Dr. Eberlein. So we are using molecular markers and genomic 
analysis of tumors. We've now identified approximately 98.6 
percent of mutations associated with human malignancy, so we 
know what those are. And now the question is can we develop a 
relational database combining genomic information with clinical 
information to be able to recommend to an individual patient 
what her treatment should or should not be.
    The greatest opportunity is probably in areas like early 
breast cancer, premenopausal breast cancer that I cited, where 
we may be able to solve this dilemma and identify the 80 
percent who don't require further toxic therapies from the 20 
percent who do. And we are now applying that kind of 
information in clinical trials through genomics and molecular 
markers from individual tumors of a particular patient.
    The same is true, by the way, in colorectal cancer, stage 
II colorectal where 25 percent of those patients after surgery 
will have a recurrence. So these are dilemmas that we face 
across many of the tumor types of cancer, but the solution is 
going to be a similar type of solution.
    Senator Blunt. And 98.6 percent of mutations being 
determined--that you can determine enough or do you need to 
have understood 100 percent of mutations or what's the range 
here where you would recommend to a patient in that foreseeable 
future that you really may not need this, but it is possible, 
so you should have chemo or we think there's almost no 
likelihood that chemo is necessary in this case?
    Dr. Eberlein. Having 98 percent, sir, is a wonderful start. 
Obviously we are looking for the remaining 1.4 percent of 
driver mutations. That said, clearly we have developed 
relational databases based on the 98.6 percent that we do know 
and are applying those in breast cancer and lung cancer and 
other leukemias and other types of cancer.

                          ALZHEIMER'S DISEASE

    Senator Blunt. Thank you. Dr. Grabowski, in your work and 
your testimony, you mentioned that if we could delay onset of 
Alzheimer's by an average of 5 years that would reduce the 
future patient cost, the future patient population, or both. 
Would you talk about that a little bit?
    Dr. Grabowski. The incidents of Alzheimer's disease 
dementia doubles every 5 years after age 65. So if you could 
delay onset by 5 years you would cut the number of cases in 
half and by inference you could cut costs in half that are 
related to Alzheimer's dementia.
    Senator Blunt. Have you looked at the NIH projections on 
taxpayer cost of Alzheimer's?
    Dr. Grabowski. Yes.
    Senator Blunt. And what are those by say 2050? I think that 
was the outside number.
    Dr. Grabowski. So the number of cases that we have on our 
hands by 2050 will probably about triple. So we are talking 
trillions of dollars of direct and opportunity costs related to 
Alzheimer's dementia.
    Senator Blunt. I think there's a $1.1 trillion number out 
there of today's dollars which would be twice the Defense 
budget would be the taxpayer----
    Dr. Grabowski. Yes.
    Senator Blunt [continuing]. Money that would be spent on 
Alzheimer's. And, you know, we deal with these big numbers like 
$1.1 trillion and how much more is that than $1.1 billion? Hard 
to get a real sense of that until you think this is twice the 
Defense budget. If your work and other's work doesn't get us to 
a better place, not to mention the individual and family impact 
of what we see here the government will be the recipient of a 
very large bill.
    Dr. Grabowski. Yes. I think that is accurate.
    Senator Blunt. Senator Murray.

          EFFECT OF PRECISION MEDICINE ON ALZHEIMER'S DISEASE

    Senator Murray. Well, thank you very much, Dr. Grabowski. 
It's great to have you out here from the University of 
Washington.
    Dr. Grabowski. Thank you.
    Senator Murray. Thanks for coming all the way across the 
country for this. University of Washington is home to one of 
the 15 Alzheimer's Disease Research Centers support with NIH 
funding and we really appreciate the great work you do.
    I understand that a particular focus of the Center is to 
identify the key differences in the way the disease progresses 
to make it feasible to develop targeted treatments for people 
with different variants of Alzheimer's. The model here is 
cancer treatment, where we have seen notable advances in 
treatment of colon cancer, for example. Can you talk to us a 
little bit about why you are hopeful that a precision medicine 
approach could speed the development of effective treatments 
for Alzheimer's?
    Dr. Grabowski. Sure. Up to this point, Alzheimer's disease 
has been treated pretty much as one thing. All of the 
epidemiological studies that you've heard about have classified 
people as having Alzheimer dementia or not.
    To a clinician who sees patients every week, it is amazing 
how many different ways people present with Alzheimer's 
disease. This is a disease with a lot of heterogeneity. Some 
people present too early. Some present much later. It doesn't 
affect all regions in the brain the same way and the pattern of 
brain regions that are involved differs across patients.
    There are factors that we don't understand that affect the 
particular pattern of involvement and the severity of 
involvement. There are other pathways that we need to 
understand besides amyloid as a driver of disease.
    When you look at recent genome wide association studies of 
later sporadic onset Alzheimer's disease, the genes that are 
being fingered are not amyloid production or processing genes, 
but things that have to do with innate immune responses, for 
example, or protein trafficking. So there are other pathways 
which are important and we need to understand which pathway is 
driving disease in which patient.
    I mentioned in my opening remarks that there are trials 
going on which are treating pre-symptomatic people that have 
genetic abnormalities that destine them for Alzheimer disease 
driven by amyloid. So those treatment trials are very important 
and they can really be considered at precision medicine trial, 
but we need other pathways to be understood and to factor into 
our work.

                           AMYLOID TREATMENT

    Senator Murray. The amyloid treatment that you mentioned, 
how early can you see that in someone that will develop 
Alzheimer's later?
    Dr. Grabowski. So we now have biomarkers that we can either 
develop from the spinal fluid or more compellingly, from 
imagining. So amyloid molecules can be detected in the brain 15 
years in advance of symptoms. And so whereas at age 65 less 
than 1 percent of people have Alzheimer's dementia, fully 20 
percent of people age 65 will have a positive amyloid scan. So 
that gives you an idea of the magnitude.
    Senator Murray. Wow.
    Dr. Grabowski. So we hear about the coming tsunami of 
Alzheimer's disease. It's a tsunami with a big iceberg in it, 
you know, of latent disease. And you can look at that as an 
opportunity because that is a period of time when you could 
intervene before symptoms have caught up with people.

          BARRIERS TO EFFECTIVE ALZHEIMER'S DISEASE TREATMENT

    Senator Murray. Wow. Well, what are the greatest barriers 
to finding an effective treatment for this, for the disease?
    Dr. Grabowski. There are several barriers. One barrier is 
we just fundamentally understand why amyloid leads to toxicity 
in the brain. There's a lot of assumptions that are made there. 
It must be important, you know, just that an extra amyloid gene 
is enough to cause a family to have Alzheimer's disease, but 
there are factors that we don't understand. There are factors 
that have to do with why some people are resilient to the 
disease. There are people that have a genetic abnormality, but 
nevertheless don't develop Alzheimer's disease until much 
later. We don't understand that.
    Education and cognitive lifestyle protect people for years. 
We don't understand what the brain mechanism of that is. We 
have relied on mouse models that haven't yet given us an 
effective treatment. We need human disease models. Some of the 
pluripotent stem cell models, as I mentioned in my opening 
remarks, are very promising for this.
    Senator Murray. That sounds like funds, money, is the key, 
right?
    Dr. Grabowski. Yes. Yes. Yes. And then that is what--that 
is actually the point of the professional judgment budget.

         PREVENTION OF HYPERTENSION AND CARDIOVASCULAR DISEASE

    Senator Murray. Yes. Yes. And, Dr. Sasser, really quickly, 
CDC relies on resources from the prevention fund to make grants 
to programs in States and communities and through national 
organizations that are focused on prevention, early detection, 
and treatment of high blood pressure. As you know given your 
research into kidney disease, hypertension not only leads to 
that disease, but is a leading risk factor for heart disease, 
which is the Nation's number one cause of death. Can you tell 
us the efforts to education patients and providers and what 
they can do to prevent the development of hypertension or 
obesity or cardiovascular disease is needed?
    Dr. Sasser. Yes, they are definitely needed. We have seen a 
huge increase in the number of obese people in our country. 
Children are developing obesity at very young ages and then 
this leads to more hypertension and cardiovascular disease. So 
these are very important focuses that we need to look at.
    Recent numbers from the American Heart Association show 
that while we now spend about $338 million a year on 
cardiovascular disease and all the consequences of that as well 
as lost work time, et cetera, those costs are expected to rise 
to $1 trillion by 2030 if prevention programs are not effective 
in stopping this epidemic.
    Senator Murray. Okay. Well, I would just say that the 
prevention fund money that is in the ACA is really critical. 
It's one of the reasons why I am very concerned about the 
repeal efforts. So thank you very much. I appreciate it.
    Senator Blunt. Thank you, Senator Murray. Senator Cochran.

                            CURES FOR CANCER

    Senator Cochran. Mr. Chairman, I am glad to welcome Dr. 
Jennifer Sasser from the University of Mississippi Medical 
Center in Jackson who is conducting research or involved in 
conducting research. I am advised that this is a research 
program that has national implications. I wonder how you can 
say about the extent to which we are making progress in finding 
a cure for cancers, whether your medical center has had 
national impact as we understood from our last hearing. I 
suppose a status report on how is it going. Are we making 
progress?
    Dr. Schultz-Cherry. We are definitely making progress. With 
the advancement in precision medicine as well as the Pediatric 
Cancer Genome Project, we've been able to understand the 
underlying in many cases mechanisms for some of the childhood 
cancers that we see at St. Jude and then to target specific 
therapies to those particular cancers. And we are sharing this 
information with pediatric oncologists around the world and 
including our techniques so that they can use those in their 
own patients as well.
    Senator Blunt. Senator Durbin.

                              NIH FUNDING

    Senator Durbin. Thanks for this hearing. Thanks to Senator 
Murray who just stepped out and Senator Alexander. Senator 
Blunt, thanks to you. You've really made history with funding 
for the NIH and I am proud to be a small part of it and to 
encourage you every step of the way. It is the most bipartisan 
thing going on in Capitol Hill and I think we are all happy to 
hear that. There shouldn't be any partisanship at all involved 
in what we are setting out to do here and so we've tried to 
keep it that way.
    We came to our efforts with the cures act, we said this is 
going to be supplemental. This is going to be additive. It 
isn't going to be in place of the NIH [inaudible]. And I hope 
we stick with that through the remainder of this year and then 
to the next year in budgeting as well. So, Senator Alexander, I 
know your personal commitment to it. You've talked to me about 
it many times. You're going to leave a great record if we do 
what we promised to do on this. Thank you for your leadership, 
again, with Senator Murray, who is a recurring theme in this 
whole conversation about medical research on the Democratic 
side.

                   DEPARTMENT OF ENERGY COLLABORATION

    Dr. Grabowski, I met with the Secretary of Energy a couple 
of years ago and talked about Alzheimer's and I talked about 
the NIH budget. And he said, ``Senator, do you have any idea 
where we are doing the research on imaging this disease?'' I 
said, ``Where would that be, Mr. Secretary?'' He said, ``The 
Office of Science and the Department of Energy.'' So can you 
tell me what collaboration is involved that you know of with 
Alzheimer's research and the Department of Energy?
    Dr. Grabowski. Well, that is a good question. I don't know 
a lot about that. The National Laboratories have been 
important. We work in our brain imaging research group at 
University of Washington with the Pacific Northwest National 
Lab and there are a number of other labs that have been pivotal 
over the years in developing PET (Positron Emission Tomography) 
imagining technology, in particular. PET imaging is becoming a 
mainstay of Alzheimer's disease research. We now have molecular 
tracers that detect, as I mentioned earlier, the amyloid 
protein, and even more exciting, the tau protein, which is the 
component of neurofibrillary tangles that really marks the 
impact of this disease. We are very excited about the use of 
tau imaging as a treatment biomarker in the future.

                     ALZHEIMER'S DISEASE DETECTION

    Senator Durbin. So, forgive me. I am a liberal arts lawyer 
and you can lose me in a second when you get into this 
conversation.
    Dr. Grabowski. Yes. Yes.
    Senator Durbin. But is it possible for you to determine 
through some imaging of my tiny brain whether or not there is 
any evidence of Alzheimer's in my future?
    Dr. Grabowski. Yes. Yes, sir. So the amyloid protein 
deposits in the brain years in advance of the symptoms. If 
someone has memory impairment and they have a negative amyloid 
scan, it is not due to Alzheimer's disease. The reason that we 
don't use this clinically is it is hard to know what to do with 
someone who's got a normal cognition and a positive amyloid 
scan. We think on average people are destined to develop 
progressive difficulty. That's an area of active research. But 
in general we can tell a decade or more in advance that someone 
has the Alzheimer process going on in the brain.

                    ALZHEIMER'S DISEASE INTERVENTION

    Senator Durbin. A year or two ago I read that two major 
pharmaceutical companies were trying to develop something to 
slow down, intervene. Did I subsequently read that it didn't 
work or what is the status?
    Dr. Grabowski. Right. So there have been a number of 
negative trials, particularly of agents which have been 
designed to glom onto and remove amyloid protein from the 
brain. In general, those studies have been given--those 
treatments have been given to symptomatic individuals with mild 
Alzheimer dementia.
    We wonder whether the failure of those trials has to do 
with the fact that it is given a little too late or maybe much 
too late. The trials which are going on now which I think are 
pivotal are the trials that are given in pre-symptomatic 
individuals that we know have amyloid driven disease who have 
mutations in the small number of genes that destine people for 
Alzheimer disease. There's two big trials going on, the DIAN 
Trials Unit, and the Alzheimer's Prevention Initiative, which 
is in a number of families and a big family that lives in 
Columbia, South America. And something called the A4 Trial, 
which is for people like us who have normal cognition but may 
have a positive amyloid scan at age 65 or older. Those studies 
are ongoing and I think, are the acid test for the amyloid 
treatment.
    Senator Durbin. Mr. Chairman, let me close with two brief 
remarks. First, Dr. Eberlein, Siteman is just recognized as one 
of the best and Barnes-Jewish in St. Louis and from my old home 
area really is a leader in research and treatment. Thank you 
for joining us as well as our other witnesses.
    Dr. Eberlein. Thank you very much.
    Senator Durbin. And let me just also say we are going to 
know in a few days what we are facing in this budget. I am 
worried. I am on the Defense Appropriations Subcommittee. 
There's talk about putting a dramatic increase in Defense 
spending. We all want a strong national defense, but if it 
comes at the expense of some fundamentals like medical research 
then we are not really serving the people that we represent as 
we should. I hope that this next President's budget is 
sensitive to those realities. Thank you.
    Senator Blunt. Thank you, Senator Durbin. Thank you for 
your leadership on this research issue, particularly, and also 
to Senator Alexander, who's been one of the real advocates 
along with Senator Moran who was the chairman of this 
subcommittee before me. I think anybody on this panel sees a 
real commitment to continuing our commitment to research and 
the impact it has on lives, as well as the impact it has on 
taxpayers, as well as the impact it has on our capacity as a 
country.
    So, Senator Alexander.
    Senator Alexander. Thanks, Mr. Chairman. Welcome to the 
witnesses. This Congress has been a little slow in finding 
things on which we can agree, but one thing we do agree on, as 
has been said, is the importance of biomedical research. And 
many of those who have led that fight are here and will 
continue to do it, I think especially of the work that Senator 
Blunt and Senator Murray did with the subcommittee. My hope is 
that we can approve the appropriation soon for the current 
year, which would give us two straight years in the 
subcommittee of increased NIH funding. And then the work that 
Senator Murray did with me and others on the 21st Century CURES 
Bill, we have a commitment there for future funding. Of course, 
Senator Durbin and Senator Cochran and Senator Moran have been 
at the forefront of that all along.
    So we will continue to do that. I think it is important for 
those working in the community to notice that when we talk 
about a $2 billion increase in 1 year for the NIH that could be 
$20 billion over 10 years. When we talk about another $2 
billion in the second year, that could be 20 more billion over 
10 years. And when we talk about $4.8 billion in the 21st 
Century CURES Bill, that is on top of that. So these are 
beginning to be significant dollars.

                         UNIVERSAL FLU VACCINE

    I want to ask Dr. Schultz-Cherry from St. Jude's--such a 
magnificent place--Dr. Francis Collins gave a little riff here 
last year about all the things, the miracles we might expect 
over the next 10 years and he talked about a vaccine for HIV/
AIDS and a vaccine for Zika and a new non-addictive pain 
medicine. But he also talked about something that most of us 
hadn't thought much about, which is a universal vaccine for 
flu.
    Now, that is something that you work on. I was surprised to 
learn that deaths from flu in the United States each year range 
from 12,000 to 56,000 individuals, compared to 493 from 
Tuberculosis, 19,000 from Hepatitis C, and 1 from Ebola. Flu is 
a real problem. You have a Center which monitors that and keeps 
after that at St. Jude's. Tell us about what you did with the 
H1N1 pandemic in 2009, the effect of the Center in keeping up 
with that, and with subsequent outbreaks, and what your 
estimate is about whether we are likely to have a universal 
vaccine for flu.
    Dr. Schultz-Cherry. Thank you, Senator. It's a fantastic 
question. During the 2009 pandemic, having one of the Centers 
for Excellence in Influence of Research and Surveillance allows 
us to be able to very much focus on emerging threats like the 
2009 pandemic where we were able to very quickly identify the 
virus, make reagents for the virus that were distributed across 
the United States, as well as begin vaccine preparation. That 
is one thing that we have to do through our World Health 
Organization Collaborating Center is we make seed vaccine 
stocks for manufacturers and for the NIH.
    And for the 2009, that was crucial in testing these seed 
stocks for safety and efficacy and it is something that we've 
continued to do, especially knowing that our vaccines are not 
as effective as we would like them to be, one of the reasons 
likely being is that we have a changing population, a lot more 
overweight and obese people and we know the vaccines do not 
work as well in this population.
    So is a universal flu vaccine in the works? Absolutely. And 
is it something that we can accomplish? Yes, I think it is. I 
think it is realistic to think that we will have a vaccine that 
will provide some protection against the strains of influenza 
that we've currently identified as well as those that we 
haven't.
    Again, we will have to--the virus is smarter than we are in 
many ways and can change very quickly, so it may require some 
changes to the vaccine, but we should be able to get much 
broader protection, including in our highest risk people, which 
are the very young, elderly, pregnant women, as well as 
overweight and obese people.
    Senator Alexander. Do you agree with Dr. Collins that could 
occur in the next decade?
    Dr. Schultz-Cherry. Yes. I actually do. I think we are 
making great strides and there's many people focused on 
creating a universal flu vaccine. And I think it is something 
that can be accomplished.
    Senator Alexander. Thank you, Mr. Chairman.
    Senator Blunt. Senator Moran.
    Senator Moran. Mr. Chairman, thank you very much. Thanks to 
our panelists, our distinguished panel for being with us today. 
And you ought to take great satisfaction in the careers that 
you are pursuing. It's a noble cause and we are very grateful, 
this country and really as a world, for the efforts that you 
make.
    I am interested in the number of people who have applauded 
Senator Blunt and Senator Murray in their efforts as well as 
Senator from Tennessee. And I certainly join in that. I also 
note how many times my colleagues have talked about how this is 
a bipartisan effort. That's certainly true. What is 
discouraging is that this is such an example of that. We 
highlight it because we are proud of it. It's been successful. 
It makes a difference, but we do that because it is the 
exception.
    And if we like what we are doing in medical research and 
the bipartisan effort that we've engendered in order to 
accomplish that, we will have to try it elsewhere. And it might 
be just as enjoyable and invoke additional pride in other 
aspects of what we do in Washington DC.
    I also wanted to follow up on the appropriations process. 
We are pleased with what we have been able to do in the past 
appropriation bills, this subcommittee and the full 
appropriations committee with Chairman Cochran's leadership, in 
regard to NIH and research dollars. What that--that is a 
pyrrhic victory if we don't do the appropriation bill. And if 
we end up with another continuing resolution for 2017, all the 
things that we've bragged about as successes will be failure. 
And my hope, and I have spoken about this on the Senate floor 
and talked to my colleagues, and hope that there is a growing 
recognition that we have an opportunity to do something this 
year in the next few weeks.
    We expect a Defense Appropriations Bill to come from the 
House, coming from the House to the Senate. We have passed 
MilCon-VA for fiscal year 2017. We will presumably pass a 
Defense Appropriation Bill for fiscal year 2017, but we need to 
take the next step and add the other 10 appropriation bills 
including Labor H so that the pat on the back that we give 
ourselves and the accolades that this subcommittee receives in 
regard to NIH actually come to fruition.
    I would encourage Mr. Chairman--Chairman Cochran, I would 
work with you and Chairman Blunt as well as our Democratic 
colleagues to make sure we don't miss this opportunity for all 
12 appropriations bills, the priorities that we've established, 
particularly here in the Labor H Bill actually become law. And 
then it sets the stage for us to do our jobs with fiscal year 
2018.
    So I hope that we can certainly take pride in what we've 
accomplished to date. We are pleased with where we've teed up 
this issue for the future, but we have an opportunity in just 
the next few weeks to take it a step further in which there's 
reality to our work for another year in a row and in my view 
would make a tremendous different for those who are 
encountering diseases and afflictions across the country and 
around the globe.
    So I am here as a subcommittee member, as a member of the 
Appropriations Committee, to work with my Republican and 
Democrat colleagues, to work with Senator Cochran, the Chairman 
of our committee, to make sure that the appropriations process 
on our--is it 150th anniversary--150th anniversary fulfills its 
mission in establishing priorities and giving direction to an 
administration.

                COMPREHENSIVE CANCER CENTER DESIGNATION

    Let me address my question to Dr. Eberlein. We are your 
neighbor to the west. We have an NCI designated University of 
Kansas facility. We are in the process of attempting to receive 
the enhanced status. What does that mean? What could you--
Siteman has received that designation, our neighbor to the 
east. What can I tell Kansans that if we are successful in 
being designated in such a manner that would mean to the people 
of Kansas?
    Dr. Eberlein. Well, it is an opportunity to expand and 
enhance the cancer care throughout that region of the United 
States. It's bringing all of the resources of the University of 
Kansas and their collaborating partners, the Stowers Institute, 
other institutions, for the wellbeing of patients.
    And that is--the NCI (National Cancer Institute) defines 
comprehensive slightly differently than most of us would think 
of comprehensive. We may think of it as being comprehensive in 
all types of cancer, but the way the NCI defines it is can you 
bring it bear all of the resources of all of the constituents 
in your locale for the betterment of patients with cancer. And 
so the University of Kansas is in the act of ability to do that 
and I think, yes, we've done that and we've tried to expand 
throughout Southern Illinois, the entire State of Missouri, et 
cetera, et cetera.
    Senator Moran. May I summarize that by saying that Kansans 
will have better opportunity for better treatment and a greater 
opportunity for cures in treatment of diseases?
    Dr. Eberlein. Absolutely. And, again, it is--one of the 
great things about the National Cancer Institute Cancer Centers 
is the exchange of information, the collaboration, the exchange 
of patients for institutions that have specific clinical 
trials. And so, again, that is one of the benefits of the 
support of NCI designated cancer centers.
    Senator Moran. Mr. Chairman, I was apparently longer in my 
rhetorical efforts than I have time. I have a couple more 
questions. I don't know whether you intend to have a second 
round.
    Senator Blunt. We'll have a second round.
    Senator Moran. Okay.
    Senator Blunt. Let's do another second round of five-minute 
round. And, Senator Murray, do you want to start?

                     TRIPLE NEGATIVE BREAST CANCER

    Senator Murray. Great. I just have a couple of questions. 
Dr. Eberlein, I wanted to ask you. I understand that since 
about 2007 breast cancer death rates have been steady in women 
younger than 50, and accounted actually for 90 percent of 
cases. Some of this is due to the fact that mammograms are less 
effective in younger women, but a lot can be attributed to the 
fact that younger women are more likely to get aggressive 
triple negative breast cancer which is obviously more difficult 
to treat.
    Can you talk to us a little bit about what the state of 
efforts to develop effective precision medicine treatments for 
triple negative breast cancer is?
    Dr. Eberlein. Absolutely. There's really two approaches, I 
think, in these younger patients who tend to have triple 
negative breast cancer. One is better imagining modalities and 
that is done through tomosynthesis, through MRI, and a 
judicious biopsy of abnormalities that are seen.
    More specific to your second part of the question, 
precision medicine ways, we have actually developed markers for 
triple negative, so we can actually separate triple negative 
breast cancers into subcategories of breast cancer so that we 
are able to tailor the chemotherapy. And then we've also 
reversed the order of these treatments. Instead of doing 
surgery as a primary intervention, we do chemotherapy first.
    I can tell you from firsthand experience, at least in our 
institution, 80 to 90 percent of these patients have dramatic 
responses to their chemotherapy upfront.
    Senator Murray. Because it is designed specifically for 
that?
    Dr. Eberlein. Because it is designed specifically for them. 
And it has two impacts. One is that it not only shrinks the 
disease, which actually makes my job doing surgery much easier, 
but it also eradicates the microscopic theoretical disease that 
is circulating looking for a home. And so we've actually seen a 
number of these patients who actually, at the time of their 
surgery, have complete pathologic responses. And so we are 
guardedly optimistic. It appears that patients are having 
actually better outcomes in the short-term, but that is, again, 
ongoing studies.
    Senator Murray. That's exciting. Keep it going.
    Dr. Eberlein. Thank you very much for the question.

                     RACIAL DISPARITIES IN DEMENTIA

    Senator Murray. Yes. Dr. Grabowski, recent studies indicate 
that dementia incidents may be highest for African Americans 
and Native American populations. While some risk factors may be 
comparable across ethnic groups, we don't really know yet the 
risk factors and brain changes in their populations that may 
differ and there have been historical challenges, as I know, in 
recruiting diverse populations for some of our research 
studies. So it is going to be really critical to engage these 
and many other groups in a participatory way to ensure that 
questions can be answered while each population's cultural 
differences are appreciated and respected.
    Can you talk a little bit about what kind of work your 
group is undertaking to reach out to those groups, and 
underserved populations, and what kind of studies you are 
conducting?
    Dr. Grabowski. Sure. So, addressing disparities, population 
disparities in Alzheimer research is one of the goals of the 
National Alzheimer Project Act.
    At our institution for the last couple of years we've been 
building an exciting new effort creating a satellite core of 
investigation of Alzheimer disease in American Indians and 
Alaskan natives. So this is got two components. It's got a 
local urban Indian outreach component and it is got a more 
nationally focused aspect which arose from an opportunity that 
came out of the Strong Heart Study.
    So Dr. Dedra Buchwald with Partnerships for Native Health 
is our collaborator and the leader of this particular effort, 
which reaches a group of, at this point, 450 American Indians 
that are reservation dwelling in Arizona, Oklahoma, and South 
Dakota, who were originally studied for heart disease risk and 
then cerebrovascular risk, and now for incidents of dementia. 
There's a lot of comorbidity in this population, so there's a 
lot of vascular disease, we are finding.
    You're right. There was a Kaiser Permanente study published 
last year which showed that dementia incidents is higher in 
American Indians than in Caucasians and African Americans, as 
you mentioned, are particularly at risk. And other centers in 
the United States have particularly strong outreach programs in 
that direction, but our focus is on American Indians.
    Senator Murray. Okay.
    Dr. Grabowski. Thank you.
    Senator Murray. Thank you very much. Thank you, Mr. 
Chairman:
    Senator Blunt. Senator Cochran.

                    INSTITUTIONAL DEVELOPMENT AWARD

    Senator Cochran. Mr. Chairman. Dr. Sasser, you mentioned in 
your testimony that your research has benefitted from the 
Institutional Development Award Program, which helps broaden 
geographic distribution of Federal research funding to States 
like Mississippi. Why is it important for biomedical research 
to take place in States like Mississippi where healthcare 
challenges are so significant?
    Dr. Sasser. Thank you, Senator Cochran. I think this is a 
good follow up to Senator Murray's question because we do have 
health disparities in Mississippi. We have a high prevalence of 
obesity, high prevalence of kidney disease, high prevalence of 
cardiovascular disease. And then a lot of that is due to the 
high number of African Americans we have in our State.
    So we do have to focus research efforts on treating these 
diseases in States like Mississippi because we see those 
firsthand. We have, being a biomedical researcher and a basic 
scientist, we have interactions with the clinicians who are 
actually seeing these diseases firsthand and we can think about 
ways to treat them more effectively. We have a long history of 
having excellent research at the University of Mississippi 
Medical Center and we are hoping to continue that by tapping 
into clinical populations to really understand why these 
diseases are so prevalent in States like Mississippi and how we 
can better treat those in the future.
    Senator Cochran. Thank you.
    Senator Blunt. Senator Moran.
    Senator Moran. Mr. Chairman, thank you. And this is one 
more thought about the broad topic, particularly as we look at 
the Affordable Care Act and its reform and alteration. A long 
time before the Affordable Care Act was ever in place there was 
a Moran 10 Point Plan on trying to improve the access to 
affordable healthcare, one that never really received a lot of 
attention. But one of those 10 point plans was further 
investment into medical research. And a number of our panelists 
have indicated how this is also a money saving--we can reduce 
the cost of healthcare. And as we work on affordable healthcare 
issues we ought to be very cognizant of how important this 
aspect and the appropriations for NIH is.

                           YOUNG RESEARCHERS

    So that I don't use up my own time and never get to ask my 
questions, I'll move forward. I wanted to highlight. One of the 
things that I was hoping you might say, Dr. Eberlein, and I 
would think this is true with comprehensive designation, but 
really with the focus on medical research. And I perhaps would 
address this to Dr. Sasser.
    One of the things I would like to be a part of in my State 
is that young men and women who are interested in science and 
mathematics and engineering and research have a place to land. 
We educate them there and too often they find places to work 
elsewhere. And I would guess that comprehensive designation is 
helpful to us in attracting and creating more opportunities and 
other facilities and researchers develop around those 
designations.
    One of the things that our States share is that we are an 
IDEA State, IDEA State. And COBRA and EMBRE are important to 
us. And I wondered if you'd take a moment, Dr. Sasser, to talk 
about how we appeal to another generation of scientists and 
medical researchers so that this country finds the cures and 
treatments, but also remains a global powerhouse in science and 
research.
    Dr. Sasser. Right. Yes. So, like I said, I have benefitted 
greatly from being a recipient of IDEA State funds. One of the 
reasons I moved to Mississippi after completing my post-doc is 
the great stability we have there. So I think, you know, as 
looking at careers, you want something that is going to be 
stable when you move your family there and get started.
    So having those funds is very, very important. It's really 
helped me as I was embarking on my career to define a new area 
of research for my laboratory. It gave me the funds to have 
those pilot projects that eventually led to the receipt of my 
RO1. And in addition with attracting new students, those are 
very important too.
    You mentioned the EMBRE program as well. We have students 
on our campus who are supported by the EMBRE, so when they're 
undergraduate research students they have the opportunity to 
come and see research firsthand, so that is very important. 
Additional programs like that include the R25 programs 
supported by the NIH that help bring students on our campus so 
we can expose them to those research careers.
    In addition, I think it is very important, as you 
mentioned, to have this stable increase in funding for NIH. As 
we have these students on campus and we have graduate students, 
it is very important that they don't see their mentors and 
investigators ramming their heads against the wall year after 
year trying to get grants. They can see people have successful 
careers and see that as a stable opportunity. So, we are hoping 
that by increasing grant funding we can have more people who 
are able to take in these students to mentor them and then show 
them that this is a very rewarding career for them, for the 
potential training of the next generation, and then as well 
helping the healthcare of Americans.
    Senator Moran. Anyone else?
    Dr. Schultz-Cherry. I think one important thing to point 
out is that the age of our first-time NIH investigators has 
changed. If you look since 1980 where predominantly less than 
people younger than 35 were having their first jobs, getting 
their first grants, we are now talking their mid-forties and 
there's more people in their late sixties with NIH funding than 
there are those people in their early forties. So it is really 
changed and it is affecting our trainees.
    Senator Moran. It perhaps is an opportunity to highlight 
the importance of elementary, middle school, high school, 
college education in regard to science and research 
mathematics. And it is not just NIH funding. It's what do we do 
to train another generation, and perhaps more importantly, 
enthuse another generation about science.
    Dr. Eberlein. One of the most rewarding aspects of my job 
is we have an undergraduate program. We get about 350 
applicants for the 15 positions that we carefully place in the 
researchers' labs. And the letters that I receive from those 
individuals who say they hadn't found their passion, but now 
they did and that is what they're going to do the rest of their 
lives. And it is actually very rewarding to have those 
individuals and then track them through college, medical 
school. I have been there long enough now that that is an 
incredibly rewarding aspect of my position.
    Senator Moran. Thank you all very much.
    Senator Blunt. Senator Rubio.

                       PEDIATRIC GENOMIC RESEARCH

    Senator Rubio. Thank you. Thank you all for being here.
    Dr. Eberlein, I have long had an interest. I am not sure I 
fully understand it from a scientific perspective, but I have 
long had an interest in genomics, genetic medicine, and the 
impact particularly on cancer. It's a fascinating--fascinated 
in your testimony about Dr. Werkman. Am I pronouncing it the 
right way, this particular case? I assume he's either a 
practitioner or research or both who himself was--and they were 
able to identify not just a specific characteristic of the 
genetic makeup of his cancer, but an off-label drug for kidney 
disease that was able to treat it.
    So the promise of this is extraordinary and it leads to the 
notion that cancer isn't really one disease. It is a millions 
and millions of variations of it and very individual specific, 
so there's a tremendous amount of promise. And you also outline 
how that can make a difference in the treatment of breast 
cancer in your own practice where about only 20 percent of the 
people impacted by breast cancer would need chemotherapy in 
addition to radiation and surgery. Imagine if we could find who 
that 20 were, not just the impact on their lifestyle and the 
improvements in their care, but on costs, both to the 
healthcare system and to their lives. So this is very 
promising.
    My question is: are we applying the same level of intensity 
and focus on an understanding of genomics and genetic medicine 
at the pediatric realm? Are we making the same progress on the 
pediatric realm as we are in the adult population? And if 
anyone else has a comment on that, I would love to hear about 
it as well.
    Dr. Eberlein. Actually, we are. Washington University along 
with St. Jude actually mapped most of the genetic mutations 
associated with pediatric tumors. And the collaboration between 
St. Louis Children's Hospital, Washington University Siteman, 
as well as St. Jude's Research Institute have create a pattern 
looking at the pathways for the cause as well as spread of 
those tumors and have identified a number of novel targeted 
treatments.
    So, again, it is actually been one of the more rewarding 
aspects of the areas of genomics. It's been particularly 
advantageous in the pediatric population and I think there's a 
plan for more investment, both at St. Louis Children's and 
Siteman Cancer Center as well as at St. Jude's.
    Dr. Schultz-Cherry. Sure. I think the genomics has really 
revolutionized how we can look at pediatric cancers. And at St. 
Jude, the ability to go from bench to bedside, making those 
discoveries and then doing targeted medicine for pediatric 
cancers has really been amazing what's happened in the last 7 
years since I have been there. It's really changing how we 
treat pediatric cancers.

                              TUMOR BANKS

    Senator Rubio. My understanding is there's an outside--just 
in the general realm of cancer there is a lot of collaboration 
nationally on tumor banks. I know there is, for example, one at 
the Moffitt Center in the Tampa Bay region. There's a lot of--
everyone is capable. Is that information widely shared across 
the research?
    Dr. Eberlein. Yes. Actually, there has been a lot of 
additional sharing among the institutions who, like Washington 
University and Siteman, have particular expertise in the 
genomic area that we have shared not only the genomic 
information--it is freely available to other institutions--but 
also with deidentified clinical information that is linked to 
that genomic information. And so these create very powerful 
databases that one can compare an individual patient with other 
patients with a similar type of fingerprint genomically and 
then develop an individualized treatment.

                   PRECISION MEDICAL AND FDA APPROVAL

    Senator Rubio. Well, so then the question I have is--and 
this is my final question given the time--I am just struggling 
to understand. How is the FDA process going to work if this 
medicine is so tailored at the individual level that there may 
be some--are the tweaks and the changes that would be required 
in treatments from patient to patient, does that apply? Do you 
foresee a point where the medicine and the treatments become so 
specialized and so specific and so different one from the other 
that it would require a separate FDA approval process that 
could complicate it and slow it down?
    I mean I can--I don't know if I am describing it the right 
way, but if there are a thousand different ways to treat the 
same cancer and the medicines have a thousand different 
formulations as a result of that if they're significant enough, 
how does the FDA process account for that as we move forward?
    Dr. Eberlein. Well, the FDA is actually expediting some of 
these personalized treatments. And again, to use Lucas 
Werkman's example, this was a drug that was FDA approved, but 
it was approved for the treatment of kidney cancer. In the case 
of Lucas, we identified that he had a specific point mutation 
that was the cause of his recurrent leukemia, not kidney 
cancer, but predicted that it would have response to this very 
targeted therapy which blocked the downstream impact of the 
gene mutation. And that is exactly what happened.
    And so I think that it is a little bit of a change in 
paradigm for the FDA that some of these treatments will be 
applicable to a different patient, but the treatment will have 
been similar and the side effects, et cetera, would be similar.

                        OFF LABEL USES OF DRUGS

    Senator Rubio. And this is just a quick--is that the only 
time--is that the first time that that drug had been used off 
label for that purpose?
    Dr. Eberlein. It has been the first time that it was used 
for a leukemia patient, yes, sir.
    Senator Rubio. And so was that--how does that now--is that 
now replicated? Has it been used again by others? How is that 
documented? How does that--does that count as a clinical trial? 
I mean, how does that work in terms of----
    Dr. Eberlein. It would be as long as a patient has had 
whole genome sequencing and that specific mutation were in the 
patient. Then you would be able to use that drug off label.
    Senator Rubio. And why I asked that, Mr. Chairman, is 
because I can foresee where some insurers will push back on I 
am not going to approve a drug that is for kidney. He doesn't 
have a kidney problem. He has a leukemia issue. And so that is 
why it is so important to document its effectiveness.
    Dr. Eberlein. Well, we've done exactly the same thing 
taking chemotherapy that is very effective in colorectal cancer 
and we identified that in about 20 percent of non-small cell 
lung cancer that the drug for colorectal cancer is actually 
very impactful. And so again, but only through genomics and 
comparing the genes and the sequences in the lung cancer 
patient and the colorectal cancer patient that we applied the 
colorectal drug to the lung cancer patient.
    Senator Blunt. Thank you, Senator Rubio.
    You know, I think that is also an argument for a general 
view that this committee has recommended to our colleagues and 
has taken that you don't always know exactly what your research 
is going to turn up. And the Congress is, in all likelihood, 
not the best place to specifically talk about how research 
dollars are allocated, particularly how they're allocated over 
some longer period of time.
    And I would say, particularly in response to the couple of 
very good observations, several good observations made about 
younger researchers, when you don't have an increase in NIH 
dollars, which we didn't have for 12 years, and you've got the 
commensurate decline in buying power, you have a decrease in 
real available dollars, and I think you referred to them, Dr. 
Sasser, as seasoned researchers who have an advantage. And Dr. 
Schultz-Cherry, you mentioned how the average age of 
researchers during that decade went up for I think pretty 
obvious reasons when you look at it which is why NIH, I believe 
on their own, determined with the increase that we did a couple 
of years ago that they were going to specifically designate 
part of that increase for young researchers to encourage people 
to stay in the field and know that there was opportunity there.
    I would also say in response to the observation that 
Senator Alexander made when this committee increased by $2 
billion the base number for research, that is $20 billion over 
10 years. And then CURES added $4 billion to that, $4.5 billion 
over 10 years. So that is in a very short period of time a $24 
billion increase.
    And then as Senator Moran pointed out, if we can do the 
budget that we are all largely in agreement on for the year 
that we are already in, that is another $20 billion over 
essentially that same 10-year period. So suddenly we go from 
where we were to a $44.5 billion increase over a decade. And 
for young researchers and all researchers and all the 
opportunity, I think everybody on this subcommittee and 
frankly, Mr. Chairman, I think on our full committee are really 
committed to this being one of our priorities which is why we 
are working so hard to see if we can't add that annual $2 
billion, 20 over 10, sometime between now and the end of April 
when we deal in some long-term way for this fiscal year with 
where we are rather than just a CR. A CR from last year would 
have been a lot better for research than a CR from the year 
before that, but a second commitment where, as Senator Murray 
and I have said both, that you don't develop a pattern in year 
one. You have to start that pattern in year two and hopefully 
maintain that over the foreseeable future.
    So, to our witnesses, thank all of you for being here. The 
subcommittee stands at recess.

                          SUBCOMMITTEE RECESS

    [Whereupon, at 12:01 p.m., Wednesday, March 8, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]