[Senate Hearing 110-]
[From the U.S. Government Publishing Office]



 
  DEPARTMENTS OF LABOR, HEALTH AND HUMAN SERVICES, AND EDUCATION, AND 
          RELATED AGENCIES APPROPRIATIONS FOR FISCAL YEAR 2008

                              ----------                              


                         MONDAY, MARCH 19, 2007

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 1 p.m., in room SH-216, Hart Senate 
Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin and Specter.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF HON. ELIAS A. ZERHOUNI, M.D., DIRECTOR


                OPENING STATEMENT OF SENATOR TOM HARKIN


    Senator Harkin. The Subcommittee on Labor, Health and Human 
Services, Education, and Related Agencies will come to order. I 
welcome you today to the hearing on the fiscal year 2008 budget 
for the National Institutes of Health.
    Whenever I talk about NIH, it is always a pleasure to sit 
with my good friend Senator Specter, who will join us very 
shortly. Maybe I should wait till he gets here so he can hear 
all the good things I've got to say about him.
    But I'll just say that no one has fought harder to improve 
biomedical research in this country. He and I worked in 
lockstep to double funding for NIH between fiscal years 1998 
and 2003, covering two different administrations. I always say 
it's one of my proudest accomplishments in my entire career in 
the Senate. I know he shares my disappointment that the NIH has 
fallen on tougher budgetary times since then.
    The fiscal year 2007 joint funding resolution that Congress 
passed a few weeks ago brought some good news. We increased NIH 
funding by $637 million, enough to launch the National 
Children's Study. We added another 500 research grants and 
provided additional funding for high-risk grants and young 
investigators.
    Even with that increase, however, fiscal year 2007 marked 
the fourth year in a row that NIH funding failed to keep up 
with the cost of inflation. In fact, since the end of the 
doubling period in fiscal year 2003, NIH funding has dropped by 
about 8 percent in real terms. That cut threatens to squander 
our Nation's investment in biomedical research, delay new cures 
and treatments, and discourage the next generation of young 
investigators from entering the field.
    The President's fiscal year 2008 budget would make matters 
even worse. On paper, it would seem to cut NIH funding by $328 
million. But the actual reduction is about $200 million more, 
so a total of about $529 million, because, under this budget, 
NIH would pick up the entire tab for the Global AIDS Fund, 
rather than sharing it with the State Department.
    So, as a result of this, comparable funding for the 
National Cancer Institute would drop by $79 million, funding 
for the National Heart, Lung, and Blood institute, by $36 
million, and the National Children's Study, which we just 
launched, would be stopped cold. I'm not ever in the habit of 
ever speaking for my good friend Senator Specter, but I think I 
can say we will not allow those cuts to take place.
    This is the first of six budget hearings on NIH that this 
subcommittee will hold this spring. At today's hearing, we'll 
hear first from Dr. Elias Zerhouni, the Director of NIH. Our 
second panel today will consist of four leading scientists who 
have received NIH grants. They will discuss the impact of 
Federal funding on their areas of research, and why it's so 
important to increase our investment in NIH. All four of these 
scientists helped produce a new report on NIH, which I got last 
week, and it's entitled, ``Within Our Grasp--or Slipping Away? 
Assuring a New Era of Scientific and Medical Progress.'' So, 
we're going to be discussing that in our second panel. This 
report will be released at a press conference immediately 
following this hearing.
    Next Monday, we'll hold a hearing with the directors of 
five NIH institutes: NINDS, NIDA, NIAAA, NIMH, and NIDCD. 
Before the spring is over, the subcommittee will hear from the 
directors of each institute and center at NIH.
    So, that's the agenda. Before I introduce Dr. Zerhouni, 
I'll yield to my good friend Senator Specter.


               OPENING STATEMENT OF SENATOR ARLEN SPECTER


    Senator Specter. Thank you very much, Mr. Chairman.
    This is a very important hearing by this subcommittee to 
hear from the director of the National Institutes of Health, 
our premier health agency in the United States, and he's the 
number-one administrator. Health is our most important capital 
asset. Without health, there is nothing any of us can do. I can 
attest to that, personally, from the medical problems that I 
have worked through.
    In 1970, President Nixon declared war on cancer, and, had 
that war been pursued with the intensity of our other wars, my 
chief of staff, a beautiful young woman, 48 years old, Carie 
Lachman, wouldn't have died of breast cancer. One of my best 
friends, a very distinguished Federal judge, Judge Edward 
Becker, wouldn't have died last year from prostate cancer. We 
all know, within our immediate circle of friends and family, of 
fatalities which have occurred because of the maladies of one 
sort or another. It is within reach to cure cancer, to find 
ways on a breakthrough on Parkinson's and Alzheimer's and heart 
disease and juvenile diabetes, and the other maladies, with 
sufficient funding.
    Senator Harkin and I, who have transferred this gavel with 
seamless efficiency from time to time, have worked on this 
matter together for decades, and we've taken the lead to 
increase in funding, sometimes on an annual basis in excess of 
$3 billion, to do the job. Well, it is simply unacceptable to 
have a $500+ million cut in NIH funding, as proposed by the 
administration this year. When you have a Federal budget of 
$2.9 trillion, an enormous sum of money, this large hearing 
room insufficient to stuff $10,000 bills into it to make, to 
make that kind of funding, to have an allocation of less than 
$30 billion, candidly, is scandalous. In an era when we are 
beset in the Congress all the time on how to reduce healthcare 
costs from the smallest of businesses to individual families to 
the biggest corporations, and the best way to reduce healthcare 
costs is to eliminate these major maladies, to prevent illness. 
We are blind, really, to this very, very, important objective.
    Earlier today I called Dr. Zerhouni and asked that he focus 
on the issue of cost savings. That seems to be an item which 
has special appeal on Capitol Hill. Elimination of disease, and 
the suffering that goes with it, ought to be our primary 
concern, but somehow if it saves dollars, it attracts more 
attention.
    We also have the issue of stem cell research which we've 
been fighting. We found out about stem cells, and their 
potential, in November 1998, and, within 10 days, this 
subcommittee held a hearing, and we've since had 20 hearings. 
Stem cells have the potential to be a veritable fountain of 
youth. We, regrettably, cannot use Federal funding on stem cell 
research, except for a few lines, which were available back on 
August 9, 2001. But if these embryotic stem cells were to be 
used to create life, no one would want to use them for 
research, but there are 400,000 available, and they're going to 
be discarded unless they're used to save lives.
    Here again, Senator Harkin and I took the lead to 
appropriate $2 million for adoption, and a few have been 
adopted, but a very few, in the range of 100, contrasted with 
400,000, which will be thrown away. So, our work is cut out for 
us.
    You have two strong allies in Senator Harkin and myself, 
Dr. Zerhouni, and you have the potential to have 533 more if 
there's sufficient political pressure brought to bear on 
Washington, DC. I've talked about a million-person march on the 
Mall. A million people could be heard in the living quarters of 
the White House. Attitudes are changed in Washington, with 
political pressure. With 110 million people affected, directly 
or indirectly by disease, that group of public opinion could 
write its own ticket. Senator Harkin and I want to be the 
scriveners.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you very much, Senator Specter.
    Dr. Elias Zerhouni has served as Director of the National 
Institutes of Health since May 2002. Prior to that, Dr. 
Zerhouni was the executive vice dean of Johns Hopkins 
University School of Medicine, chair of the Department of 
Radiology and Radiological Science, and Martin Donner professor 
of radiology and professor of biomedical engineering. Dr. 
Zerhouni received his medical degree from the University of 
Algiers School of Medicine, completed his residency in 
diagnostic radiology at Johns Hopkins.
    I might just add that since May 2002, every report that 
we've gotten, every indication, all the people that we've 
talked to, both in NIH and out in the countryside, have 
basically reported that Dr. Zerhouni has done an outstanding 
job of leading NIH since he's been there.
    With that we welcome you back to the committee, Dr. 
Zerhouni. Your statement will be made a part of the record in 
its entirety. They had set it for 5 minutes; I said boost it up 
to 10, and, if you need more than that, we'll give you more 
than that.
    So, please proceed as you so desire.


              SUMMARY STATEMENT OF HON. ELIAS A. ZERHOUNI


    Dr. Zerhouni. Thank you very much.
    It's my pleasure to appear before you, Mr. Chairman and 
Senator Specter. There couldn't be more passionate supporters 
of science and research than both of you. As I've worked with 
you over the past 5 years, I have to be, also, a witness to not 
only your passionate support, but also your profound 
understanding of what makes science, and what makes medical 
research, work, and why it is so important to the Nation.
    I also would like to thank you and the committee for your 
personal support for the increased funding for NIH in 2007 and 
the focus that you have brought towards supporting the next 
generation of scientists, and making sure that we do not become 
stale in our research, that our momentum is kept, in terms of 
new breakthroughs.
    What I'd like to do is attract your attention to the slide 
and give you a very short summary of the essence of where we 
think NIH as a whole is going and why we're directing our 
efforts into what we would call a new era in medicine.


                         VISION FOR THE FUTURE


    We need to have a vision for the future as a country. I 
think it is absolutely clear that the 21st century will be for 
the life sciences what the 20th century has been for the 
physical sciences. Mastery of the biological world will impact 
not just health, but also our ability to develop sensitive 
solutions to our environmental and energy challenges, and will 
be, in my opinion, a key determinant of national 
competitiveness for the 100 years in front of us. It is 
important to sustain our momentum in that regard.
    I'd like to, first, point out to you that NIH has been, and 
continues to be, a very, very productive investment for the 
American people. We are living longer and healthier. Let me 
give you some specifics.
    For the second consecutive year, annual cancer deaths in 
the United States have fallen. This is an unprecedented event. 
This has not occurred in any other country. It has not occurred 
for the time that we've had records. The absolute number of 
deaths decreasing is happening at the same time that our 
population is increasing in number and aging, at the same time.
    What has been the investment that each one of us has made 
in that regard, in the war on cancer? On average, each American 
has spent about $9 per year, from 1974 to 2004, to accomplish 
these results, which are still insufficient. The complexity of 
cancer is such that we need to accelerate our research, not 
slow it down.
    If you look at heart disease, there's been a remarkable 
drop in mortality from heart disease and stroke. In 2004, for 
example, a drop in death for women with heart disease has 
dropped from 1 in 3 to 1 in 4. More importantly, as Senator 
Specter was pointing out, the economic value of this drop in 
mortality and morbidity is estimated at $1.5 trillion to $2.5 
trillion per year. This is the kind of result that I think we 
can foresee for the future. What has been the investment? About 
per year per American for each year over the past 30 years.
    More importantly, I think it is clear that disability is 
decreasing among older Americans. It has dropped by 30 percent 
in the past two decades. Life expectancy has risen to 78 years, 
up 6 years since 1974. What has been the average total 
investment per American per year at NIH? Only $44 per year for 
medical research.
    I think we can say that NIH has been a good investment, and 
continues to see itself as the vanguard for changing--changing, 
not just how we cure disease once the disease has struck us, 
but how we really advance our research to make a profound 
difference in what I think is our concern today, and that is 
the challenge of rising U.S. health expenditures. Biomedical 
research must deliver, and NIH is poised to deliver.
    If you look at the percent of GDP consumed by healthcare 
costs, and its upward curve, it is clear that this will be one 
of the greatest challenges facing our society, because this 
growth rate of healthcare expenditures is not sustainable in 
the long run.
    Historically, medicine has been reactive, and patients did 
not seek attention until an acute event required them to seek a 
doctor's cure. But our system of care has been based on 
managing these late events on an episodic basis. Is there a 
better vision? Is there a way science can help the country 
tackle this problem? I think there is. When you look at the 
projection of doubling of our costs in 10 years, to $4.1 
trillion a year, I think one cannot but feel that there is a 
real race against time to discover new ways of practicing 
medicine.
    Let me be clear. If we practice medicine in 25 years the 
way we practice it today, we will have lost the game of the 
century. It is very important that we understand that. Is there 
a paradigm in the future that will change that? The answer is 
yes. We need to advance the science that will allow us to pre-
empt disease.


                        PARADIGM FOR THE FUTURE


    I think if you look at this chart, you can divide any 
disease into three stages. One is what we call the preclinical 
stage, the bottom yellow band, where people do not know that 
they have a disease. We may not know that someone has a 
disease, because chronic diseases, which are the dominant 
factor in our healthcare cost, can begin 20-25 years before 
they become clinically obvious. Then symptoms start to appear, 
and we can intervene at that time. This is what we call the 
tolerable or compensated phase of a disease. Last, but not 
least, is the uncompensated phase, where, typically, curative 
treatment tends to occur.
    What we've done over the past 30 years is try to move back 
in time to try to address diseases before the critical phase. 
But, in the future, what we see with the advances we've made in 
the past 10 years is, that for the first time--the complexity 
of biology and the advances we've made in science tell us that 
we could start to understand disease years before it strikes by 
understanding the first molecular events that lead to disease 
and intervening at that time. The potential cost savings are 
enormous, because, as the white curve shows, costs increase 
exponentially with the typically late interventions that we 
today practice. It is much more expensive to take care of heart 
disease in the late stages than to try to prevent it with an 
intervention very early in the life cycle of the disease.
    That is, in my view, the vision of the future. This is how 
NIH research can potentially provide new insights, which we do 
not have today. But it is clear that the opportunities are 
there. Our scientists are doing an enormous amount of work in 
discovering, every day, new targets to understand the complex 
diseases that harm our people. We need to maintain the momentum 
of that research.
    Let me just show you an example here of a disease called 
rheumatoid arthritis. This is a patient's hands at early stage, 
middle stage, and late stage. How are we going to improve 
costs? How are we going to make a change in the natural history 
of this disease? Obviously, in the late stage, not much can be 
recovered, and managing that late stage is quite expensive. 
We've made progress over the past 10 years. There's a new class 
of antirheumatic drugs that dramatically slows disease 
progression by focusing on a factor called tumor necrosis 
factor and reducing the impact of that factor. But that is not 
enough. We really need to go earlier in the disease process. 
That's why, in 2006, for example, genetic discoveries have 
revealed new genes, which we didn't know about 3 years ago, 
before the--at the end of the doubling of the NIH budget. The 
completion of the human genome in 2003 has allowed us to 
accelerate this kind of discovery. But every time we find a 
gene, that means more research has to be done on that gene, 
because the gene is only the code of what may be wrong in that 
disease. Much more research lies ahead of the discovery of a 
gene. Therefore, it is important for us to see that this 
research continues so that, in the future, we will pre-empt by 
intervening on the very fundamental factors that lead to that 
disease, and hopefully eliminate the costs of that disease.


     4 P'S--PREDICTIVE, PRE-EMPTIVE, PREVENTIVE, AND PARTICIPATORY


    So, the future paradigm, if you will, if I can summarize 
it, is what we call the 4 P's.
    One, using the new technologies we've developed, the new 
insights we've developed over the past 10 years, there is 
potential for us to be much more predictive about to whom, how, 
when a disease will occur. By using gene-chip technology, we 
can, today, do that in several diseases.
    Second, treatments are going to have to be personalized. 
Every one of us is different, and we react differently to 
different therapies. That's the second P.
    Third, we have--through that knowledge, we have to become 
pre-emptive. But this will also require a revolution in the way 
we conceive of healthcare. Instead of a disease-based 
healthcare system, or healthcare system driven by disease, we 
should focus on a healthcare system drive by health, where 
patients are not sick, patients are healthy when they come in 
contact with us. That will mean people will have to participate 
a lot more in their care than ever before. That means 
transformation of the healthcare system, driven by new science. 
This is what I call the Era of Precision Medicine. This is what 
we're working for. This is what NIH's vision has been, and 
continues to be. More importantly, we feel that we are at the 
edge of being able to do that.


                           PREPARED STATEMENT


    NIH and its scientists deeply believe that we are in the 
transformative phase of the biomedical and behavioral sciences, 
where opportunities for discoveries and their translations--
translation have never been greater. We believe that we're on 
the path to do that. We want to encourage not only the current 
generation of scientists, but the future generation of 
scientists, to come unhampered, and to be supported, because 
this is the race of the century. In the 21st century, no nation 
will prevail unless it prevails in the life sciences.
    Thank you very much.
    [The statement follows:]

              Prepared Statement of Dr. Elias A. Zerhouni

    Good afternoon, Mr. Chairman and distinguished members of the 
subcommittee. It is an honor and a privilege to appear before you today 
to present the National Institutes of Health (NIH) budget request of 
$28.9 billion for fiscal year 2008, and to discuss the priorities of 
NIH for this year and beyond.
    I would first like to thank the Committee for your longstanding 
support of NIH, including in the fiscal year 2007 Joint Resolution that 
provided additional support.

                              INTRODUCTION

    The 21st century will be for the life sciences what the 20th 
century has been for the physical sciences. Mastery of the biological 
world will impact not just health, but also our ability to develop 
sensitive solutions to environmental and energy challenges and will be 
a key determinant of national competitiveness. One of the greatest 
challenges facing our society is the unsustainable growth rate of 
healthcare expenditures. NIH and its scientists deeply believe that we 
are in a transformative phase of the biomedical and behavioral 
sciences, where opportunities for discoveries and their translation 
have expanded considerably. We believe that we are on a path to 
transform medicine from the current practice of intervening often too 
late in a disease process, to a new era when medicine will be more 
predictive, personalized and preemptive, through a broader scientific 
understanding of the fundamental mechanisms that lead to disease years 
before it strikes the patient. In a relatively constant budget, we made 
the tough but necessary choices to ensure that the investment and 
momentum of biomedical research continues.
    A more predictive, personalized and preemptive form of medicine is 
no longer just a dream but a vision to strive for, because it can 
reduce disease burden and its costs while improving individual quality 
of life.
    Last year, I discussed the return on the Nation's investment in 
biomedical research. Today, I will highlight some of the progress we've 
made in the last 12 months and where we must be in the future to create 
a sustainable environment for the discoveries needed to transform 
people's health.

                    THE IMPACT OF PAST NIH RESEARCH

    NIH-supported research of the past several decades has contributed 
to dramatically improved health outcomes across many diseases and 
conditions. For instance, we have made remarkable advances in coronary 
heart disease, the leading cause of death in the United States for the 
past 80 years. Were it not for ground-breaking research on the causes 
and treatment of heart disease, supported in large part by NIH, heart 
attacks would still account for an estimated 1.6 million deaths per 
year instead of the actual 452,000 deaths experienced in 2004. Our 
Nation has had particular success in reducing fatal heart disease in 
women. In February of this year, NIH's National Heart, Lung and Blood 
Institute announced that the number of women who died from heart 
disease decreased by nearly 18,500 deaths from 2003 to 2004. Part of 
this success is attributed to NIH's efforts to increase awareness among 
women that heart disease is their number one killer.
    The mortality rates of cancer, the second-leading cause of death in 
the United States, have been steadily falling. This year, for the 
second year in a row, the absolute number of cancer deaths in the 
United States has declined despite the growth and aging of our 
population--a truly unprecedented event in medical history. More 
effective therapies have also led to improved outcomes for more than 10 
million American cancer survivors. In 2006, new clinical guidelines 
were announced for the treatment of advanced ovarian cancer. And for 
another of our most deadly cancers, melanoma, a new gene therapy 
approach resulted in sustained regression of advanced disease in a 
study of 17 patients, whose own white blood cells were genetically 
engineered to recognize and attack cancer cells.
    Nearly 21 million Americans have diabetes, a disease that can 
damage multiple organs and lead to death. Without NIH research, the 
improvements of the past two decades in the therapies for diabetes 
would not have occurred, and we would have many more cases of the 
dreaded complications of diabetes, including blindness and end-stage 
kidney disease. Our research has shown the enormous benefits to be 
gained by tightly controlling blood glucose levels in diabetes. The 
NIH-funded Diabetes Control and Complications Trial confirmed that 
individuals with diabetes can cut their risk for nerve disease by 60 
percent, and half their risk for kidney disease and cardiovascular 
disease by intensively controlling their blood glucose levels. Our 
diabetes research has also shown that tight glucose control can slash 
the risk for eye disease by more than 75 percent--a critical finding 
for the estimated 24,000 Americans who lose their sight to diabetes 
each year. In fact, diabetic retinopathy is the leading cause of 
blindness in adults under age 65.
    The treatment of cognitive decline and mental disorders continues 
to improve at an incredibly rapid pace. In 2006, NIH supported the 
development of new strategies that helped depressed patients become 
symptom-free and prevented disease recurrence in older adults with 
single-episode depression.
    Other noteworthy advances from 2006 included the development of 
promising new drugs for tuberculosis, inflammatory disease and muscular 
dystrophy, as well as exciting experimental results of vaccines against 
increasingly dangerous staph infections and against the H5N1 avian flu 
virus. Last year we also launched a trial for a new and promising 
vaccine against HIV/AIDS, and just last month, our scientists' 
discovered a unique molecular weak spot in the armor of the HIV virus, 
which could have profound implications for vaccine development.
    In brief, thanks to the Nation's investment in biomedical research, 
we have learned to diminish the harmful impact of many diseases and 
disabilities for all Americans. The estimated total cumulative 
investment at the NIH per American over the past 30 years--including 
the doubling period--is about $1,334, or about $44 per American per 
year over the entire period. Over the same time period, Americans have 
gained over 6 years of life expectancy and are aging healthier than 
ever before. New industries such as biotechnology, based on NIH-funded 
discoveries, have led to the creation of thousands of companies in the 
life sciences with impact beyond health. The American people's return 
on their investment in NIH is truly spectacular.

                           CURRENT CHALLENGES

    In short, the many scientific advances achieved by NIH-funded 
researchers--over many decades--now allow our population to live longer 
and healthier lives. But as our population continues to age, a striking 
change becomes evident. The burden of our Nation's health problems has 
dramatically shifted from acute to chronic diseases. Chronic diseases 
now consume over 75 percent of healthcare costs and continue to grow at 
a rapid pace. Profound lifestyle changes have led to the emergence of 
non-communicable diseases such as obesity and attendant growth in the 
prevalence of associated conditions, such as diabetes and heart, kidney 
and musculoskeletal diseases. It is important to note that the burden 
of these chronic diseases is not uniformly distributed among our 
population; health disparities remain a critical health issue that 
requires new and continuing efforts.
    Let me now present a sobering reality. Despite medical progress, 
healthcare costs in the United States have risen to more than $2 
trillion, or about 16 percent of the Gross Domestic Product (GDP), and 
they grow at a rate greater than the GDP. The average amount spent on 
healthcare per person is about $7,100 today. The causes of healthcare 
inflation are varied and complex, but it is clear that this growth rate 
is unsustainable in the long term and will impose an enormous burden on 
our people and the competitiveness of our Nation. Biomedical research 
alone will not solve all of these problems, but it is an essential 
component toward a sustainable future. NIH and its scientists 
understand the need to reduce the impact of this great challenge 
through transformative discoveries and their rapid translation from 
laboratory to patients.
    While seeking medical discoveries that will address ongoing 
concerns, we must also be prepared to confront new and unpredictable 
threats. Emerging and re-emerging infectious diseases are on the rise, 
as micro-organisms develop strategies for evading our best drugs. We 
face the rapid globalization of mass transportation and the staggering 
worldwide threat of HIV/AIDS and other familiar foes. We must stand 
ready for the threat of pandemic influenza and of man-made bioweapons 
for which we have greatly expanded our investments in the past several 
years. Addressing these many new threats will require sustained 
scientific efforts and further breakthroughs.
 strategic vision for the future: from curative to preemptive medicine
    Historically, medicine has been reactive, and patients did not seek 
attention until an acute event required them to seek a doctor's cure. 
Our system of care is based on managing these late events on an 
episodic basis--an increasingly costly and unsustainable approach. What 
then is the scientific vision for change? Our goal at NIH is to usher 
in an era where medicine will be predictive, personalized and 
preemptive. This trend will also require a transformation in the 
fundamental relationship between healthcare providers and patients, 
necessitating continuous participation of individuals, communities and 
healthcare institutions as early as possible in the natural cycle of a 
disease process.
    Based on NIH-supported research, we now know that many of the most 
prevalent diseases of our time begin silently, many years before they 
inflict their obvious damage to patients. Increasingly, we are able to 
identify biomarkers that are predictive of the likelihood of developing 
a serious condition later in life. Just in the past year, we have 
discovered genetic variations that help predict the development of age-
related macular degeneration, a major cause of late-life blindness. We 
also discovered a new gene associated with Alzheimer's disease, a major 
control gene for diabetes and a marker of genetic susceptibility to 
prostate cancer. The genetic marker for prostate cancer risk came from 
the NIH-supported Cancer Genetic Markers of Susceptibility (CGEMS) 
study. Through the CGEMS database, genetic information about prostate 
cancer risk will be shared with cancer researchers across the country. 
The mining and sharing of genetic information will provide much-needed 
information to help us develop new strategies for the early detection 
and prevention of prostate cancers, which take the lives of nearly 
27,000 American men each year and disproportionately affect African 
Americans.
    Just consider, for a moment, how more predictive and personalized 
treatments could improve the safety and effectiveness of drugs. We know 
that drugs do not fall into the ``one size fits all'' category. The 
same drug can help one patient and harm another. Recent research shows 
that we will be increasingly able to know which patients will benefit 
from treatment and which patients might be harmed. This field of study 
is known as pharmacogenetics. Using the latest genomic data--acquired 
thanks to the doubling of the NIH budget--the NIH established a 
Pharmacogenetic Research Network, which is studying the interactions of 
drugs and molecules, as well as the biological processes that eliminate 
compounds from the body.
    As an example of emerging personalized medicine, cancer researchers 
have developed a test that helps to determine the risk of recurrence 
for women who were treated for early-stage, estrogen-dependent breast 
cancer. This information can help a woman and her doctor decide whether 
she should receive chemotherapy, in addition to standard hormonal 
therapy. The test has the potential to change medical practice by 
identifying tens of thousands of women each year who are unlikely to 
benefit from chemotherapy, sparing them from unnecessary and costly 
treatments and their harmful side effects. Such a test is now being 
readied for FDA review and is being evaluated in a long-term clinical 
trial sponsored by the NIH's National Cancer Institute.
    Ultimately, this individualized approach--completely different than 
how we treat patients today--will allow us to preempt disease before it 
occurs. We have already benefited greatly from these insights. For 
example, we know that controlling blood pressure, cholesterol levels, 
weight and diet, and eliminating smoking, greatly reduce the risk of 
heart disease and lung cancer. Mortality from colon cancer has dropped 
because our scientists have shown that such cancers evolve from 
accumulated genetic mutations in initially benign colon polyps which, 
if removed, preempt the development of lethal cancers.
    Because of a hundredfold reduction in the unit cost of genomic 
technology, we can now study, at affordable costs, the differences 
between patients who have a disease and their normal counterparts. 
These breakthroughs form the basis of our budget request for the 
continuation of the Genes, Environment and Health Initiative started in 
2007 and strongly supported by Secretary of Health and Human Services 
Michael Leavitt, who is also championing the concept of personalized 
medicine across all of HHS. With this new initiative, we expect to 
uncover--within three years--the potential molecular causes of the 10 
most common diseases afflicting the U.S. population. As part of this 
initiative, we will also launch a technology development effort that 
will enable scientists to measure many types of environmental exposures 
at the individual level.
    Taken together, these studies will lead to better understanding of 
the environmental and genetic factors that affect the development of 
many diseases. Imagine that your heart rhythm, brain activity, blood 
pressure and many other variables could be remotely monitored through a 
device like your cell phone and sent to a secure web-based analyzer 
with direct access to experts and a modern health information system. 
Suppose, for example, that these technologies could identify dangerous 
patterns in your heart rhythms or key biomarkers and warn you of an 
impending heart event or stroke or other complications. Imagine your 
doctor could tell--based on your genes--whether you need to take 
preemptive action to thwart a costly or painful disease, or whether you 
can avoid taking expensive medications for life because you are not at 
risk. This is not some science fiction. NIH is supporting the 
development of that future today.

      MAINTAINING MOMENTUM TOWARD 21ST CENTURY MEDICINE AND HEALTH

    Building toward the future involves innovations in multiple areas, 
including technology, research and training paradigms, information 
interoperability, and greater knowledge and resource management. We 
have seen an explosion of new discoveries and novel opportunities for 
progress across all areas of science--from the most basic discoveries 
to the sequencing of the human genome, to the development of fields 
that simply did not exist a few years ago. These emerging fields 
include proteomics, computational biology, or more recently the 
discovery of RNA interference, for which two NIH-funded scientists--
Drs. Craig Mello and Andrew Fire--received the 2006 Nobel Prize in 
Physiology or Medicine.
    The greatly expanded scope of research and new health challenges 
have necessitated a dramatic expansion of the Nation's research 
capacity, which was a primary outcome of the doubling of the NIH 
budget. This remarkable growth in research capacity was accomplished by 
leveraging NIH resources with private sector resources to nurture more 
investigators, develop new technologies and build infrastructure.
    The United States is now the preeminent force in biomedical 
research, and continues to lead the highly competitive biotech and 
pharmaceutical sectors, but it is also the focus of increasing 
challenges from government-supported research in Europe and Asia. NIH 
basic research and training programs produce steady streams of novel 
discoveries and innovative people that flow into our industries, making 
them more competitive. Multi-national corporations often choose to set 
up facilities here, to tap into the American pool of talent and 
research nexus, both largely developed through NIH funding.
    NIH-funded research leads to patents and spin-off companies across 
the Nation. Through the Small Business Innovation Research (SBIR) and 
Small Business Technology Transfer (STTR) programs, NIH helps to 
support entrepreneurs, as they bring to the international market 
products that improve health and help to maintain American economic 
leadership. Thus, NIH research and training dollars leverage state and 
private investment, resulting in powerful academic research centers and 
entire geographic regions for greater creativity and productivity.
    The American health research enterprise now has the capacity to 
achieve extraordinary medical advances and economic benefits for the 
Nation, and we must continue this momentum. We must sustain the 
capacity we have worked so hard to build and harness its potential.
    The talented scientists and institutions we have nurtured are 
stepping up to the challenge. For example, NIH now receives twice as 
many applications for grants than before the doubling of its budget. 
Due to the marked competition for funds across so many novel areas of 
research and health challenges, competition for grants and the quality 
of projects submitted to NIH is better than ever. We anticipate that 
the fiscal year 2008 budget will again support about one-fifth of 
applications submitted, as opposed to one-third in fiscal year 2003. We 
focused our budget request on maximizing the number of competing grants 
for new and established scientists. To encourage innovation and sustain 
the next generation of scientists to the greatest extent possible, we 
have also developed programs for new investigators and for pioneering 
high-risk/high-impact investigator-initiated research, the mainstay of 
fundamental discoveries.
    To achieve our vision of modern medicine, we also need research 
scientists with broad expertise, from widely varied disciplines, coming 
together in highly cooperative and efficient teams to answer ever-more 
complex questions. To this end, NIH recently changed a long-held policy 
of having only a single principal investigator on any NIH grant to a 
new policy that allows, when appropriate to the science, multiple 
principal researchers to apply for a grant together. This new policy is 
encouraging collaboration across disciplines and enabling academic 
scientists to exercise creative leadership in a project while bringing 
more of the best and brightest from physical, biological and behavioral 
sciences to the task of solving the multifaceted and complex health-
related problems.
    As biomedical research becomes more comprehensive, and we recognize 
that complex diseases come under the purview of more than one or a few 
NIH Institutes and Centers, we have been stimulating collaborative 
endeavors through multiple trans-NIH activities, such as the NIH 
Roadmap for Biomedical Research. These trans-NIH activities focus on 
providing the impetus and support for high-risk/high-impact research 
through Pioneer Grants; developing tools and new scientific teams for 
furthering our understanding of the complexity of biological systems; 
and stimulating a large effort to re-engineer the Nation's clinical and 
translational research enterprise to support more effective 
interactions between laboratory research and its clinical translation.
    In 2006, we launched the Clinical and Translational Science Awards 
(CTSA) Program, which is the first in-depth redesign of our system of 
applied research in 50 years. The CTSA Program is stimulating research 
institutions to foster more productive collaboration among 
investigators in different fields. The program also encourages creative 
organizational models and programs for training the next generation of 
clinician scientists, without whom much basic research cannot be 
applied to human populations. Ultimately, patients will be better 
served because new prevention strategies and treatments will be 
developed, tested and brought into medical practice more rapidly.
    In addition, the NIH Intramural Research Program is launching 
several initiatives to make even more effective use of the highly 
talented scientists and state-of-the-art resources in our federal 
laboratories.
    We have made every effort to generate greater synergies between NIH 
Institutes and Centers. For example, the NIH Strategic Plan for Obesity 
Research was launched in 2003 and involves 19 Institutes. The 
Neuroscience Blueprint brings together 15 NIH Institutes and Centers 
and the Office of the Director, pooling resources and expertise to 
confront challenges in neuroscience research that transcend any single 
Institute or Center.
    NIH is also taking advantage of emerging information technologies 
and is making management changes in response to public health needs. We 
are working to modernize our governance and improve efficiency. For 
example, the Office of Portfolio Analysis and Strategic Initiatives 
(OPASI) is developing a new knowledge management-based system, which 
performs text mining on NIH projects for more efficient research 
portfolio analysis. This tool will provide our Institutes and Centers 
with the information needed to more effectively manage their large and 
complex scientific portfolios, identify important emerging scientific 
opportunities and public health challenges, and target investments to 
those areas. OPASI will be invaluable for supporting key trans-NIH 
initiatives being incubated through the NIH Common Fund, which is a 
central feature of the NIH Reform Act of 2006.
    We would like to take this opportunity to thank Congress for 
passing this landmark legislation, which will enable NIH to modernize 
its organization; incubate innovative ideas and potentially ground-
breaking research; address emerging areas of scientific opportunities; 
stimulate support of cross-cutting science; and encourage collaborative 
efforts while preserving the ability of Institutes and Centers to 
continue their outstanding record in fulfilling their specific 
missions. We are diligently working to implement this legislation.

    BUDGET PRIORITIES: NURTURING A NEW GENERATION OF SCIENTISTS AND 
                         SUSTAINING INNOVATION

    New visions require new talent. One of NIH's highest priorities 
will be to preserve the ability of new and junior scientists with fresh 
ideas to enter the competitive world of NIH funding. We plan to use the 
additional funding provided to NIH in the fiscal year 2007 Joint 
Resolution on these valuable initiatives. In fiscal year 2007 and 2008, 
we will make every effort to maintain an average yearly number of 
approximately 1,500 new investigators receiving their first NIH R01-
equivalent grants to create the vital next generation of scientific 
leaders.
    Also in fiscal year 2008, the NIH budget proposes to continue to 
grow fresh talent through the new ``Pathway to Independence'' program 
and to support 175 recently trained scientists in their quest to become 
independent researchers at an earlier point in their careers. These 
efforts, however, cannot come at the expense of the need to provide 
continuing support to our most productive and already established 
scientists. History shows that no one can predict from whom and from 
where the next great discovery or life-saving breakthrough will occur. 
It is therefore critical that NIH maintain a large variety of 
approaches to science and continue to work hard to encourage diversity 
among its scientists across all strata of our society.
    We also strive to maintain the historical balance between the 
critically important investigator-initiated research portfolio and 
agency-driven priorities. Our successful model of research is based on 
creative and unconstrained scientists who propose their best ideas, so 
we can subject those ideas to rigorous and independent peer review, and 
then support the most promising and high-quality projects. Our budget 
targets resources to providing as large a number of competing Research 
Project Grants for individual scientists as possible. To support our 
vision and initiatives in the current budget environment, we made 
difficult but strategic decisions, like maintaining the average cost 
for competing grants at the fiscal year 2007 level and not providing 
inflationary increases for direct reoccurring costs in non-competing 
grants. Our budget also proposes to reduce intramural research 
expenses.
    Our basic science projected percentage in fiscal year 2008 is 54.1 
percent, and applied science is projected at 42.1 percent. The percent 
of NIH's budget designated for infrastructure support will increase 
slightly in fiscal year 2008, to 3.2 percent. In total, the budget 
provides $144 million to enhance our infrastructure stewardship to 
provide robust, modern, energy-efficient, and environmentally safe and 
secure facilities to conduct basic and clinical research.

                                SUMMARY

    In closing, let me emphasize--we are at a critical point in 
biomedical research and must maintain the momentum to reach our vision. 
The opportunities for significant advances exist on virtually every 
front. We must not let these opportunities slip away. We do not want to 
lose the scientific capacity that we have developed in the recent past 
across the entire country. The transformation of health and medicine 
from the curative paradigm of the past to the preemptive paradigm of 
the future is within our grasp. As an example, in the past year alone, 
we realized a huge victory against cervical cancer, a disease that 
affects hundreds of thousands of women worldwide--a victory that we 
only dreamed about 10 or 15 years ago. The discoveries of Drs. Doug 
Lowy and John Schiller of NIH's National Cancer Institute on the human 
papilloma virus and the hard work of our private-industry partners have 
led to the development of the first FDA-approved vaccine against 
cancer. This is the kind of preventive intervention that will help us 
transform medicine in this century. The development of this vaccine 
represents just a small example of the NIH contribution to 
biotechnology and its transfer to the bedside--in this case before the 
``bedside'' is ever needed.
    We are also working to preempt disease through evidence-based 
education that draws on the best behavioral and social science 
research. Let me give you just one of the many examples of how NIH 
translates research results into practical health interventions for the 
public. In 2005, NIH launched the WE CAN (Ways to Enhance Children's 
Activity & Nutrition) program. WE CAN is a behavioral intervention at 
the level of communities aimed at preventing childhood obesity. The 
overwhelming response from around the country has been gratifying. In 
less than two years, individuals and groups--ranging from schools and 
youth organizations to community and recreation centers--have joined 
with NIH and our partners in 36 states to energize WE CAN. This is what 
I mean when we talk about the necessary participation of communities 
and individuals in their own health in a future redesigned healthcare 
system.
    NIH also continues to expand its outreach and participatory efforts 
through its website, one of the most-visited in the word. The NIH 
website averages about 47 million visits each month, with more than 330 
million page views.
    I ask you to consider the challenges and the opportunities before 
us today in medicine and health, and the essential role of biomedical 
research. We have the key elements in place for overcoming a host of 
diseases and conditions and their societal burden, and momentum is on 
our side. Our research efforts have ushered in revolutionary changes in 
the diagnosis, treatment and prevention of disease. Sustaining the pace 
of biomedical discovery is essential to realizing a true and necessary 
transformation of medicine and health in our country.
    I will be happy to answer any questions you may have. Thank you.

    
    
    

    Senator Harkin. Dr. Zerhouni, thank you very much for a 
very enlightening and succinct presentation.
    I've been fond of saying a lot in the past that in America 
we don't have a healthcare system, we have a sickcare system. 
When you get sick, you get care. There's not much up front to 
help keep you from getting sick. A statistic I saw recently was 
that 75 percent of all medical cost in Medicare is due to the 
treatment of chronic illnesses which have reached their later 
stages. So, a lot of these are preventable, if you get to them 
early on. That's what you're showing here, to get to a true 
healthcare system, where you keep people healthy in the first 
place.
    So, I really appreciate that presentation. I think that's a 
good note on which to begin our questioning.

                           STEM CELL RESEARCH

    Dr. Zerhouni, I have a series of questions, and then I'll 
yield to Senator Specter. We may go back and forth here for a 
while. But the first thing I want to get into is something that 
Senator Specter brought up. Both of us worked together on this, 
very hard. Senator Specter had the chairmanship during all 
those years when we first isolated embryonic stem cells, in 
Wisconsin, at the University of Wisconsin. Senator Specter had 
the first hearings on that. As he said, we've had 20 since 
then. He and I have worked together harmoniously on this to try 
to push the frontiers of this and to get around the 
restrictions.
    But when you were appointed to your position 5 years ago, a 
lot of people were anxious about what we were going to do about 
embryonic stem cell research and about the restrictions that 
were placed on August 9, 2001, at 9 p.m. At that time, you 
know, there was a limit of how many stem cell lines could be 
financed through Federal funds for research. We were told, at 
that time, there were 78. But then, we've found out a lot since 
then.
    Now, again, when you first came before this committee, you 
said you wanted to let science take its course. Well, over the 
last 5 years, science has taken its course. I thought that was 
profound on your part to do so, to say that, because what we've 
discovered is that those 78 lines are not 78, they're really 
about 21. At least that's the latest I've been told. Only a 
handful are used on a regular basis, limiting their genetic 
diversity. We know, also, that all of them have been 
contaminated, because they were grown on mouse feeder cells. 
So, the likelihood that they would ever be used for any human 
intervention is unlikely. We now know that there are much 
better ways of deriving and growing stem cells than what we 
knew in 2001. However, the lines derived from these new methods 
are not eligible for Federal funding.
    So, given all that's happened in the last 5 years, I'd just 
like to revisit this issue with you. With everything you've 
told us about the vision for the future and getting in front of 
this, would scientists have a better chance of finding these 
new cures, new interventions for diseases, if the current 
restrictions on embryonic stem cell research were lifted?
    Dr. Zerhouni. I think the answer is yes. My experience has 
been this. In 2001, I think the policy that was put in place 
was the first one to fund embryonic stem cell research. I think 
NIH has done a great job in the first 3 years of that in 
establishing infrastructure, funding new scientists, which 
weren't fundable before. Since 2004, I think it's very clear, 
from the point of view of science and what I have overseen, 
that these cell lines will not be sufficient to do all the 
research we need to do, for the reasons that you mentioned, but 
the most important one is that these cell lines have exhibited 
instability, from the genetic standpoint, and it's not possible 
for me to see how we can continue the momentum of science in 
stem cell research with the cell lines that we have currently 
at NIH that can be funded. So, from my standpoint, it is clear 
today that American science is--would be better served, and the 
Nation would be better served, if we let our scientists have 
access to more cell lines, because they can study with the 
different methods that have emerged since 2001, the different 
strategies that we now understand, underlie the fundamental 
issue, which is nuclear programming, or DNA programming, or 
reprogramming.
    So, the answer is yes.
    Senator Harkin. Well, Dr. Zerhouni, let me ask you to 
comment on two things, then.
    We're hearing a lot now in the popular press, not so much 
in the scientific journals, that we don't have to do this, that 
adult stem cells can take care of it all, then we have amniotic 
stem cells, and then we have umbilical cord stem cells, and 
that we don't need embryonic stem cells, that all these others 
will handle it, will take care of it.
    Second, on the issue of stem cell research itself, why is 
it so important that NIH do this? Already, California is doing 
it. I think Missouri just passed a constitutional amendment on 
it. In Iowa, my own State, the legislature just voted, and the 
Governor signed a law lifting the ban, in Iowa. Wisconsin, of 
course, New York. So, different States are doing different 
things. A lot of times when I talk about this, people say, 
``Well, if the States are doing it, there's no real reason for 
NIH to be involved in this.'' So, if you could address both--
why is it important for NIH? What about adult stem cells and 
all these others being sufficient?
    Dr. Zerhouni. Well, let me give you my point of view, and, 
I think, the scientific point of view here. Again, my statement 
that I--as I made 5 years ago, is that I will always stick to 
the scientific truth, and disease knows no politics. So, let me 
say this. The presentations about adult stem cells having as 
much, or more, potential than embryonic stem cells, in my view, 
do not hold scientific water, if you will. I think they are 
overstated. I think we do not know, at this point, where the 
breakthroughs will come from. I think scientists who work in 
adult stem cells, themselves, will tell you that we need to 
pursue, as vigorously, embryonic stem cells.
    My point of view is that all angles in stem cell research 
should be pursued. I think people sometimes misunderstand what 
the fundamental challenge is in stem cell research. It's not 
solely to use it to replace things, like in adult stem cell 
transplantation, but it's to really understand, for the first 
time in the history of mankind, how DNA is programmed and 
reprogrammed. Well, to do that, you need to have copies of 
cells that have been programmed--adult stem cells--but also 
copies of cells that have never been programmed forward--
embryonic stem cells. The key thing here is that the nation 
that understands that will be as--in the stronger position, as 
we were in the 20th century for the information revolution, for 
computers. It's basically the software of life that we're 
talking about. So, from my standpoint as NIH Director, it is in 
the best interests of our scientists and our science, our 
country, that we find ways, that the Nation finds a way, to 
allow the science to go full speed across adult and embryonic 
stem cells equally.
    Senator Harkin. Why is it so important for NIH?
    Dr. Zerhouni. Right. So, why is it important? As the NIH 
Director, I can tell you that the role that NIH has played in 
this country over the years has been second to none. There is 
no State that can really provide the depth of oversight and 
stimulation of this research over the long run. This is not a 
1-mile race; this may be a marathon. It is important, I think, 
for NIH to play its historical role. I think that we have done 
that. We can do this, with appropriate oversight, a lot of 
safeguards, to make sure that this research is not misused.

                 NIH'S LEADERSHIP IN STEM CELL RESEARCH

    Senator Harkin. Ethical guidelines.
    Dr. Zerhouni. Ethical guidelines. You know, Senator, we've 
done this. We've done this with the Recombinant DNA Advisory 
Committee in 1976, 1977, 1978. At that time, as you know, 
genetic engineering came on the scene. There was a huge 
question about both the safety and the ethics of using genetic 
engineering. Well, NIH took the lead, and set up a Committee 
called the Recombinant DNA Advisory Committee. We've been 
probably the most successful country in biotechnology. We've 
created a completely new industry. I think that this is the 
kind of role NIH can play. If you have a patchwork of policies, 
a patchwork of different approaches, you may not have the same 
standards. It will be very difficult for our country to muster 
its strength unless we have some sort of moving--of move 
forward in this area. We cannot, I think, be second-best in 
this area. I think it is important for us not to fight with one 
hand tied behind our back here.
    Senator Harkin. I also----
    Dr. Zerhouni. NIH is key to that.
    Senator Harkin. I also see what's happening out there now 
in California, where they're in a bidding warfare to get 
scientists to come there. Missouri's now going to do some 
bidding. Wisconsin. I suppose Iowa will probably get in the 
game now that we've lifted the law. So, it just seems that--to 
me, anyway--by providing NIH with this authority, which--you 
have the experience, the oversight, you are the world's leader. 
Everyone recognizes NIH as being the gold standard of unbiased 
research--that if you put NIH's blanket over the thing, I think 
it would reduce, a lot, this kind of bidding warfare between 
States, and then we'd have a national kind of an approach on 
this. Plus, NIH could reach out to other countries and 
coordinate other countries in doing this research, also. Is 
that, sort of, the kind of process would take place?
    Dr. Zerhouni. My view is that I think it's time to move 
forward on--in this area. It's time for the Nation's 
policymakers to find common ground to make sure that NIH does 
not lose its historical leadership. I think we've maintained 
that leadership all the way to 2004-2005. But, as we've 
discovered, the lines that we have are less viable than we 
would have liked them to be--as these lines are older, I think 
it's important to realize that we need to move forward here, 
and NIH needs to continue its historical role as the leader of 
biomedical research in the world. To sideline NIH on an issue 
of such importance, in my view, is shortsighted. I think it 
wouldn't serve the Nation well in the long run. We'd need to 
find a way to move forward. I look at--obviously----
    Senator Harkin. Yeah.
    Dr. Zerhouni [continuing]. It's more than science that is 
involved here, but I hope that we can find that way forward 
soon.
    Senator Harkin. Well, Dr. Zerhouni, let me thank you for a 
very profound and courageous statement that you've made here 
today.
    Dr. Zerhouni. Thank you.
    Senator Harkin. Thank you.

                      DECLINE IN CANCER DEATH RATE

    Senator Specter.
    Senator Specter. Dr. Zerhouni, as you have testified, the 
deaths due to cancer have declined in the last 2 years. To what 
extent would you attribute that to research done by NIH?
    Dr. Zerhouni. It's difficult to figure out exactly what is 
contributing to what, but I can be somewhat specific. Most 
scientists look at this decrease and feel that the main cause 
has been the decrease in smoking, that behavioral changes--
social and behavioral sciences have contributed to epidemiology 
and prevention a great amount. The second cause has been early 
screening. If you look, for example, at colon cancer, the rates 
of colon cancer, and the death rates, have come down. Why? 
Because we have promoted the early detection of polyps. Now, 
how does NIH play into that? Well, it turns out that the 
discovery that told us that polyps are really the pre-emptable, 
the preventable cause of the cancer, was that the genetic 
changes that lead to cancer start with a polyp. So, it's a----
    Senator Specter. So, it is the NIH research which has 
identified a way for early screening to treat cancer at an 
early stage.
    Dr. Zerhouni. But the basic research----
    Senator Specter. Is that correct?
    Dr. Zerhouni. That is correct, Senator. The most important 
is the NIH basic research, the study--the findings of Dr. 
Vogelstein, for example, who discovered that cancer of the 
colon does not happen overnight, but happens through a cascade 
of genetic changes that start with a polyp. That's what then 
led to the development of screening, and its impact on the 
reduction of cancer rates.
    Senator Specter. NIH has researched and found treatments 
for various strains of cancer, isn't that correct?
    Dr. Zerhouni. Absolutely.

                          UNDERSTANDING CANCER

    Senator Specter. How many strains of cancer are there? We 
talk about cancer as one generalized term, but approximately 
how many different strains of cancer are there?
    Dr. Zerhouni. That's an excellent question, Senator. Most 
people will say 200 types of cancer are known. But my view is 
that, as I've followed this field very closely--is even within 
breast cancer, for example, there are many subtypes of breast 
cancer. So, if you look at cancer, it's not one disease, it's 
200 separate diseases, and the molecular changes that occur in 
each one of them may actually be different from one to the 
other. This is why we need to do more research, to understand 
what's different between a cancer that kills and a cancer that 
doesn't, and how do you treat this one versus that one?
    Senator Specter. We have had estimates, on prior hearings 
by this subcommittee, on how long it would take to cure 
Parkinson's. Would you say that it would be realistic to give 
an approximation as to what it would cost to cure cancer, and 
how long it would take?
    Dr. Zerhouni. Very difficult to do that, as you know.
    Senator Specter. Well, that's why I'm asking you, Dr. 
Zerhouni.
    Dr. Zerhouni. I appreciate that, Senator. I think it's 
clear that if you look at the advances that we're making today, 
that the--the challenge in front of us is to understand the 
complexity of cancer treatments relative to the complexity of 
the biology of cancer. Most people would say that in the area 
of Parkinson's disease, for example, that there are--we need to 
make progress at the basic level to understand what are the--
what is the first mechanism of disease. We have several 
mechanisms of disease that we are working on. As long as you 
don't know that, it's very hard to predict when you're going to 
cure Parkinson's disease. But we're already studying--knowing, 
for example, which genes are involved in Parkinson's disease. 
We've made discoveries that tell us that Parkinson's disease 
relates to abnormalities in the neurons. Some people think it's 
because there's accumulation of abnormal protein mechanisms. 
But here is the answer. The answer is, I can assure you that 
with less research, the cure will take much longer than with 
more research.
    Senator Specter. Well, that's a pretty obvious conclusion, 
Dr. Zerhouni----
    Dr. Zerhouni. I know. Well, it's like the question----
    Senator Specter [continuing]. But----
    Dr. Zerhouni [continuing]. You posed, Senator.

                       QUANTIFY FUNDING DECISIONS

    Senator Specter [continuing]. But what we are looking for, 
within reason, is finding some way to quantify it. Now, I've 
had some experience with Hodgkins, and I have been informed of 
a variety of advances in the treatment of Hodgkins. Different--
they call it a cocktail--that wasn't my idea of a cocktail 
before I had Hodgkins--and they told me a complex 
categorization and various substances. I've talked to others, 
and the field has progressed tremendously. All for the better. 
What would be very meaningful, as we approach your budget, 
would be to try to get some way to quantify, as best you can--
now, I know this is not going to work out to be a mathematical 
formula, but, when we talk about the various strains of cancer, 
it is important to know how many research projects are 
undertaken, and how many you are turning away.
    We moved, on this committee, to appropriate very 
substantial sums over a 4-year period of time. From fiscal year 
1999, we increased the budget to slightly under $2 billion--
$1.950 billion. The next year, we appropriated the increase was 
$2.190 billion. The year following a $2.630 billion increase. 
The year following, an increase of $2.830 billion. The year 
following, an increase of $3.770 billion. So that we are able 
to increase funding over a 5-year period, some $13 billion.
    Now, how did we do that? We took a budget in the range of 
$140 billion, which the subcommittee has, which funds three 
very important departments, Health and Human Services, 
Education and Labor and we pruned through the budget, found, 
with very sharp pencils, where we could establish priorities to 
increase the funding for NIH.
    Now, you've testified, in the past, that increase in 
funding enabled you to grant many, many more applications for 
funding. More recently, we have seen a decrease. Senator Harkin 
and I had to fight like tigers last year to add a little over 
$600 million to stop a $50 million cut in the National Cancer 
Institute. Now, what catches the attention of our colleagues 
would be specifics. So, my request to you--and I've made 
similar requests in the past--is to go back and make an 
analysis, and give us your best judgment as to what is 
happening with the decrease in the funding. The President's 
budget now is more than $500 million below last year, without 
considering an inflationary increase. We would like to know 
what effect that's going to have on research, so that--tell us, 
number one, your best judgment as to what it would cost to cure 
cancer, or as close as you can to that analysis, taking the 
strains of cancer and how many research projects you need, and 
over what period of time; and then, second, what's going to 
happen to NIH if the budget is cut by more than $500 million. 
If you take an inflationary factor of 2 percent, it's several 
billion dollars that it's being cut. Then, the third factor 
that would be very helpful would be to tell us what would be 
done by way of prevention. It's very expensive to treat 
somebody with Hodgkins. I can tell you that personally. Your 
statistics are also impressive when you say that the second 
year in a row there's been a 60-percent drop in mortality for 
heart disease and strokes. That means 60 percent fewer people 
have died. The drop in deaths of women from heart disease, from 
one-third to one-fourth, reported.
    [The information follows:]
 
              Professional Judgment Cost to Cure Cancer

    If I may: ``What will it cost if we do not cure cancer?''. The 
National Institutes of Health estimate overall costs for cancer in 2006 
as $206.3 billion: $78.2 billion for direct medical costs (total of all 
health expenditures); $17.9 billion for indirect morbidity costs (cost 
of lost productivity due to illness); and $110.2 billion for indirect 
mortality costs (cost of lost productivity due to premature death).\1\  
Between 1974 and 2004, on average, each American has spent about $9.00 
per year on cancer.\2\  Moreover, economists at the University of 
Chicago, Graduate School of Business have estimated that a 1 percent 
reduction in cancer mortality would be worth $500 billion to current 
and future Americans. A ``war on cancer'' that would spend an 
additional $100 billion on cancer research and treatment would be 
worthwhile if it has a 1-in-5 chance of reducing mortality by 1 percent 
and a 4-in-5 chance of doing nothing at all.\3\ 
---------------------------------------------------------------------------
    \1\ American Cancer Society, Cancer Facts and Figures 2007.
    \2\ Congressional Transcripts, Congressional Hearings, March 19, 
2007, page 5: Senate Committee on Appropriations, Subcommittee on 
Labor, Health and Human Services, Education and Related Agencies Holds 
Hearing on the Fiscal year 2008 Budget for the National Institutes of 
Health.
    \3\ Murphy KM, Topel RH: The value of health and longevity, J 
Political Economics: vol. 114, no. 5, pages 871-904.
---------------------------------------------------------------------------
    The primary focus of the NCI is on research and developing 
prevention and treatment options; it is necessary for others in the 
cancer community to ensure that the results of our efforts are 
disseminated and applied.

                          COST TO CURE CANCER

    It is probably unrealistic to predict when cancer will be cured. 
Cancer is not one disease, but represents over 200 diseases and as a 
result is an exceptionally complex health care problem. Eliminating 
cancer as a significant burden will require step-wise gains in 
scientific knowledge and innovative ways for translation of this 
knowledge to the clinic. Progress is made by building upon pre-existing 
discovery, and the pace of scientific advances is, of course, driven by 
the amount of resources available for laboratory research and clinical 
translation. The NCI has never been at a more exciting place in terms 
of understanding the molecular mechanisms causing cancer and 
determining its progression. We have made tremendous progress over the 
last decade that has resulted in a measurable decline in cancer deaths 
for both men and women. Three decades ago there were 3 million caner 
survivors; today there are over 10 million.
    What can also be said with certainty is that we are rapidly moving 
toward an era when cancer treatment will involve a molecular diagnosis 
of each tumor followed by highly personalized recipes of therapy. We 
are identifying the underlying genetic changes identified with the risk 
of developing cancer, we are increasingly able to detect cancer before 
clinical symptoms, we are learning how to use the immune system to keep 
cancer from progressing, and we are developing therapies that 
specifically target cancer cells. Using these combinations of 
approaches to prevention, diagnosis and treatment, we are beginning to 
see some cancers as manageable chronic diseases.
    Of great concern is the knowledge that cancer incidence is 10 times 
greater for those 65 and older than for those under 65, and the death 
rate is 16 times higher. By 2030, 20 percent of the U.S. population 
will be over age 65 compared with 12 percent in 2004. Therefore, it is 
imperative that we maintain, if not accelerate, the momentum of 
scientific discovery.

                  BUDGET CUT BY MORE THAN $500 MILLION

    The following examples illustrate what NIH can't do with the fiscal 
year 2008 President's Budget, relative to the fiscal year 2007 enacted 
level:
National Cancer Institute
    Despite many fruitful studies on prostate cancer initiation and 
progression, the prostate cancer cell of origin has not been 
conclusively identified. NCI will not be able to fund an R01 on the 
``Study of the Cell-of-Origin and Cancer Stem Cells in Prostate 
Adenocarcinoma'' which seeks to identify the prostate cancer cell of 
origin--an understudied area in cancer biology. In this highly focused 
application, the investigator would test the hypothesis that, in the 
prostate, there is a specific progenitor cell population that is 
sensitive to oncogenic transformation, and that this cell population is 
also responsible for hormone resistant prostate cancer formation. The 
application is innovative, timely, and likely to yield significant 
meaningful data that will drive the future of the field. Because most 
current therapeutics target what may be a more differentiated cell 
type, the success of this proposal could lead to novel strategies for 
treating prostate cancer. There are very few applications currently 
funded to identify cancer stem cells in prostate cancer.
National Institute on Alcohol Abuse and Alcoholism
    The most serious adverse consequence of prenatal alcohol exposure 
is fetal alcohol syndrome (FAS), a devastating developmental disorder 
characterized by craniofacial abnormalities, growth retardation, and 
nervous system impairments that may include mental retardation. 
Preliminary data suggests that pharmacological and nutritional 
interventions may prevent deficits in alcohol-exposed fetuses even when 
administered following the exposure to alcohol. Recently studies in 
animal models have shown that choline is capable of preventing deficits 
due to alcohol exposure in utero. The fiscal year 2008 President's 
budget does not provide sufficient funds to proceed with larger scale 
studies to determine the effectiveness of choline in preventing 
deficits in humans due to in utero alcohol exposure.
National Institute of Child Health and Human Development
    There will be no expansion of research efforts to translate NICHD-
supported basic scientific findings into a new class of antimicrobial 
agents that could prevent bacterial or viral infections in the 
gastrointestinal tract, overcoming a major and growing public health 
problem of bacterial and viral drug resistance. Researchers found that 
oligosaccharides, non-nutritive components of human milk, inhibit the 
toxic effects of Escherichia coli and other gastrointestinal pathogens. 
These pathogens infect thousands of adults, and children, annually, 
causing extreme discomfort and even death. In the U.S., infections due 
to C. jejuni, E. coli, and five other food borne pathogens have been 
estimated to cost $6.5 billion to $34.9 billion annually. The critical 
advantages of developing these amazing antimicrobial products are that 
they: a) can prevent both viral and bacterial infections, and b) do not 
interfere with protein synthesis and bacterial/viral replication. 
Instead, these compounds prevent the pathogens from binding to 
intestinal walls, thus overcoming a major and growing public health 
problem of bacterial and viral drug resistance.
National Institute of Diabetes and Digestive and Kidney Diseases
    NIDDK can provide only very limited funding to solicit applications 
investigating the effect of maternal obesity on mechanisms that could 
potentially contribute to obesity, diabetes, cancer, cardiovascular or 
metabolic disease in the offspring.
    NIDDK has not been able to initiate an Autoimmune Hepatitis 
Clinical Research Network which would focus upon elucidating the 
pathogenesis and developing means of prevention, treatment and control.
National Institute of Neurological Diseases and Stroke
    The NINDS developed the Spinal Muscular Atrophy (SMA) Project as a 
pilot of how to speed the translation of basic science advances to 
therapies that are ready for clinical testing. The project is 
implementing a systematic drug development plan via a ``virtual pharma 
organization,'' which develops and applies the resources for drug 
development through subcontracts to companies that serve the 
pharmaceutical industry. The project is making encouraging progress, 
enough so to warrant application for a provisional patent on promising 
compounds that have been developed. Although there are other 
neurological disorders that might be ripe for a similar targeted 
therapy development program, NINDS would not be able to undertake such 
an activity under the President's budget.
National Institute on Aging
    Specific examples of the potential impact of budget constraints on 
the momentum of the federally-supported Alzheimer's disease research 
agenda include:
  --NIA may be unable to maximize data collection efforts or to 
        capitalize on the data being generated through studies under 
        its two recently-released Program Announcements aimed at the 
        discovery, development, and preclinical testing of novel 
        compounds for the prevention and treatment of Alzheimer's 
        disease.
  --NIA will fund fewer studies under the Alzheimer's disease 
        Neuroimaging Initiative, a public-private partnership that 
        tests whether imaging techniques, other biological markers, and 
        clinical and neuropsychological assessment can be combined to 
        measure with greater sensitivity the progression of mild 
        cognitive impairment (MCI) and early Alzheimer's disease.
  --Constrained budgets could slow the process of studying and 
        identifying genes through the ongoing Alzheimer's disease 
        Genetics Initiative, which is designed to develop the resources 
        necessary for identifying late-onset Alzheimer's disease risk 
        factor genes, associated environmental factors, and the 
        interactions of genes and the environment. Identification of 
        informative subjects, genetic typing, and data analysis would 
        all be slowed, delaying the identification of genetic and 
        environmental factors that could provide new approaches for the 
        prevention and treatment for Alzheimer's disease.
National Institute of Allergy and Infectious Diseases
    There is an intensified need for the development of a safe, 
effective and acceptable topically applied chemical and /or biologic 
barrier to prevent sexually transmitted HIV infection. Topical 
microbicides hold great promise as a strategy for preventing future HIV 
infections and AIDS-related complications and are designed to allow 
women to protect themselves against HIV and other sexually transmitted 
infections. The NIH supports several research programs and initiatives 
to help develop and advance candidates into human clinical trials, 
including the Integrated Preclinical/Clinical Program for HIV Topical 
Microbicides, Microbicide Innovation Program, and the Microbicide 
Design and Development Teams. There are 38 lead microbicide candidates, 
of which seven are advancing to clinical trials in the next few years, 
and over 100 proposed candidates in the microbicide development 
pipeline. Additional funds would allow NIAID to ensure a vibrant 
pipeline and advance five additional compounds into early clinical 
studies.

                          PREVENTION RESEARCH

    The following examples of prevention research should lead us toward 
the era of personalized medicine, where we will be able to preempt the 
disease early in its process or even before it starts.
National Institute of Mental Health
    NIMH is supporting a prospectively designed research network to 
predict, characterize, and preemptively treat schizophrenia:
  --Schizophrenia is generally diagnosed between ages 18 and 21 when a 
        young person has a psychotic episode that requires 
        hospitalization and intensive treatment.
  --However, most people with schizophrenia are ill for at least 18 
        months before their first psychotic episode--this period is 
        known as the prodromal phase of the illness.
  --The goal of this research network will be to determine whether 
        treating schizophrenia during the prodromal phase can prevent 
        psychosis and functional disability. Researchers will identify 
        genomic and imaging biomarkers to define risk and to develop 
        interventions.
National Institute on Alcohol Abuse and Alcoholism
    NIAAA is supporting research to identify ``trait'' biomarkers which 
are inborn characteristics of increased vulnerability for specific 
types of alcohol-use disorders including alcohol dependence 
(alcoholism).
    Through the identification of trait biomarkers for the specific 
subtypes, early pre-emptive interventions would be feasible in 
individuals at high risk for future alcohol dependence, as would 
interventions in early stages of the disease itself with personalized 
treatment based on subtype.
National Institute of General Medical Sciences
    Part of the difference in how people respond to drugs is due to 
genetic variations, particularly in the pathways that control drug 
metabolism. Such variations can render some drugs ineffective in 
certain individuals or, in other cases, increase the likelihood of 
dangerous adverse drug reactions. Since 2000, NIGMS has led the 
Pharmacogenetics Research Network, a trans-NIH effort to elucidate the 
genetic basis of differences in drug responses and guide the 
implementation of this knowledge into clinical practice. In several 
cases, findings by network scientists have already impacted practice, 
such as by providing genetic tests to support the use (or avoidance) of 
a given drug. Pharmacogenetics is a leading example of how investments 
in the Human Genome Project will broadly affect medical treatment, in 
this case by personalizing drug therapy.
National Eye Institute
    The Age-related Eye Disease Study2:
  --The Age-Related Eye Disease Study (AREDS), a multi-center study of 
        cataract and age-relate macular degeneration (AMD) originally 
        launched in 1992, demonstrated that high-dose antioxidant 
        supplements (beta-carotene, vitamins C and E, and zinc) can 
        slow the progression of AMD. Additional studies have suggested 
        that the nutritional supplements lutein/zeaxanthin and omega-3 
        long chain polyunsaturated fatty acids might have benefit in 
        preventing or slowing the progression of AMD and the formation 
        of cataract. Leveraging these findings, the NEI began the Age-
        Related Eye Disease Study2 (AREDS 2), a multi-center study that 
        will include up to 100 clinical sites.
  --It is hoped that data from ARESD2 will improve therapeutic regimens 
        that can prevent or slow the progression of AMD and cataract. 
        It is further hoped that additional study data from AREDS2 will 
        help create prognostic criteria to determine who will likely 
        benefit from these nutrient supplements.
National Human Genome Research Institute
    To speed research on the causes of common diseases such as asthma, 
arthritis, the common cancers, diabetes, and Alzheimer's disease, the 
Department of Health and Human Services announced in February 2006 two 
related groundbreaking initiatives in which NHGRI will play a leading 
role. Using the newly derived HapMap, both of these initiatives will 
search for the specific DNA variations that are associated with 
increased risk for common illnesses. Finding the DNA variants that 
predispose a person to common disease is one of the highest priorities 
of current biomedical research, since it will enable the identification 
of new drug targets and the development of personalized medicine.
    The Genes, Environment and Health Initiative (GEI) is a trans-NIH 
research effort to combine comprehensive genetic analysis and 
environmental technology development to understand the causes of common 
diseases. GEI will support more than a dozen studies, beginning in 
fiscal year 2007.
    The Genetic Association Information Network (GAIN) is a related 
public-private partnership between the NIH, the Foundation for the NIH, 
and private sponsors including Pfizer and Affymetrix. In 2006, GAIN 
selected six research studies for support: psoriasis, ADHD, 
schizophrenia, bipolar disorder, major depression and diabetic 
nephropathy. Results will begin to appear in June 2007.
National Institute of Neurological Diseases and Stroke
    Research funded by NINDS has identified specific variants of a gene 
called phosphodiesterase 4D (PDE4D) that significantly increase the 
risk of stroke in women aged 15-49. The risk is magnified in women who 
smoke cigarettes. The study is the first to identify a possible 
interaction between this gene and an environmental factor in triggering 
stroke.
    This study is part of a larger effort called the Stroke Prevention 
in Young Women Study2, which is designed to identify genetic and 
environmental risk factors for ischemic stroke (stroke that results 
from blockage in artery) in young women. The NINDS-funded investigators 
are now carrying out a study of risk factors for early-onset stroke in 
young men to help further clarify the role of the PDE4D gene and 
characterize the genetic basis for ischemic stroke. This research could 
help identify those at risk for stroke so that they may modify their 
behavior and eliminate certain environmental influences (e.g., smoking) 
to pre-empt the occurrence of a stroke. The research may also help in 
the development of new types of interventions to prevent stroke in 
those high risk individuals.
National Institute of Dental and Craniofacial Research
    Salivary Diagnostics.--The day is approaching when a tiny computer 
chip glued to a tooth will allow early, personalized diagnosis and 
treatment by closely monitoring levels of proteins associated with 
specific diseases, as well as the medications prescribed to treat them.
  --NIDCR support helped develop the current generation of rapid HIV 
        antibody testing that uses intraoral fluid. The 
        OraQuickTM HIV test reportedly has a 99.8 percent 
        accuracy rate, compared to 99.9 percent for a blood test.
  --Current grantees recently fabricated the first disposable, low-cost 
        miniaturized diagnostic platform to process small amounts of 
        saliva to detect the levels of DNA sequences of interest. The 
        work is proceeding to ultimately create a fully functional 
        hand-held instrument for salivary diagnostic tests that is 
        about the size of a BlackBerryTM.
  --In the future, miniaturization of the technology will allow 
        salivary diagnostic chips to be attached to a tooth for 
        continual personalized monitoring of biomarkers for specific 
        diseases.
 National Institute of Arthritis and Musculoskeletal and Skin Diseases
    The NIAMS places a high-priority on studies to identify risk 
factors and biomarkers of disease. To this end, the Institute will 
continue its commitment to a novel public-private partnership to 
improve prevention of osteoarthritis (OA), or degenerative joint 
disease. The Osteoarthritis Initiative (OAI) is a long-term effort, 
developed with support from numerous NIH components, private sector 
sponsors, and with the participation of the Food and Drug 
Administration, to create a publicly-available research resource to 
identify and evaluate biomarkers of OA for use in clinical research. 
The study has 4,800 participants who are at high risk for knee OA and, 
as of early fiscal year 2007, clinical data from approximately 2,000 of 
them were available for research projects. Over the next 5 years, the 
OAI will provide an unparalleled, state-of-the-art longitudinal 
database of images and clinical outcome information available to 
researchers worldwide to facilitate the discovery of biomarkers for 
development and progression of OA. In this effort, a biomarker would be 
a physical sign or biological substance that indicates changes in bone 
or cartilage. Today, 35 million people--13 percent of the U.S. 
population--are 65 and older, and more than half of them have 
radiological evidence of OA in at least one joint. By 2030, an 
estimated 20 percent of Americans--about 70 million people--will have 
passed their 65th birthday and will be at increased risk for OA.
National Institute of Diabetes and Digestive and Kidney Diseases
    Preempting Risk Factors for Type 2 Diabetes in Children:
  --Previously considered a disease of adults, type 2 diabetes is now 
        increasingly observed in children, particularly minority youth. 
        Identifying new strategies to preempt risk factors for diabetes 
        is extremely important because recent data estimate that 1 in 
        14 children in the U.S. between 12 and 19 years of age has pre-
        diabetes--and many of the children with pre-diabetes have risk 
        factors for cardiovascular disease (CVD).
  --In August 2006, the NIDDK launched a multicenter clinical trial, 
        called HEALTHY, which is aimed at preempting risk factors for 
        type 2 diabetes in middle-school children.
  --Half of the 42 enrolled schools are receiving the intervention, 
        which consists of: environmental changes to school food service 
        and physical education class activities; behavior change 
        activities; and communications and promotional campaigns.
  --Children are being enrolled in the sixth grade and followed for 3 
        years. Importantly, the schools have large (50 percent or more) 
        minority or under-served populations.

                      NIH OFFICE OF WOMEN'S HEALTH

    Senator Specter. Now, we go back to before your time, Dr. 
Zerhouni. It was about 1991, wasn't it, Senator Harkin, when 
the woman's branch of NIH was established? Is that correct?
    Dr. Zerhouni. That's correct. The Office of Women's Health.
    Senator Specter. There wasn't an Office of Women's Health 
before this subcommittee picked it up and found the money for 
it. My wife pointed out to me the difference in heart disease 
for women, and we took the lead, here in this subcommittee, to 
establish a women's unit. So, it's very gratifying to see your 
statistics this year, that heart disease of women dropped from 
one-third to one-fourth.
    Well, you get my point. I'd like to have it in a concrete 
form so that we could tell our colleagues, on the budget 
resolution. As I told you earlier today, Senator Harkin and I 
are going to be going to the floor and asking for an increase 
in the budget resolution on NIH. I'm not sure how much it's 
going to be. We're going to ask for the most we think we can 
get--that is realistic--that we can get adopted, maybe a little 
more than that in terms of bargaining. Last year, we increased 
the budget for the subcommittee by $7 billion. But that's 
confederate money on the budget resolution. Doesn't turn into 
real cash until you have an allocation.
    I had a disagreement with Senator Byrd, back in 1988, on 
the allocation for the budget, and I did the unheard of thing 
for a Senator my age compared to a Senator of his standing, to 
disagree with a chairman's mark. I got three votes. It was 25 
to 3. You may think three votes out of 28's not many, but it's 
a lot. Senator Byrd told me, at that time, ``Someday you'll be 
chairman of the Appropriations Committee.'' It didn't seem 
possible. But now I'm right behind Senator Cochran. With term 
limits and a change in party, I'm getting pretty close to that, 
Dr. Zerhouni. If, and when that happens, you won't have to 
provide all these fancy statistics. But, in the interim, we 
need them--something really concrete that we can point to--to 
show our colleagues, as a way of elevating the status of health 
and how much NIH means to promoting health, our greatest 
capital asset, and how much it means in reducing costs by 
preventing disease.

                SUSTAINING OUR PRESENT RESEARCH CAPITAL

    What do you think, Dr. Zerhouni?
    Dr. Zerhouni. Let me just give you the three points that I 
think are essential, in terms of policy, and then also take the 
opportunity to supplement that answer with specifics for the 
record.
    First and foremost, you asked the question about: What is 
the optimal way for us to accelerate our research to get to 
cures as optimally as possible? It's hard to give an answer for 
any one disease, but I can show you, from my standpoint as a 
science administrator, what I think the optimal point is in our 
ability to sustain research.
    Let me show you, if you don't mind, a slide, here, of what 
has happened to NIH success rates. Historically, we've funded 
about 3 grants in 10 applications. Today, we fund 2 in 10. Our 
experience, as--myself, as a scientist, when I ran my lab; as a 
dean for research at a major institution; and now as NIH 
Director, is that 3 in 10 is the historical percentage where 
NIH has always sustained its success rate, and where we've 
gotten the return that we wanted. I'm concerned that 20 percent 
is too low. I think you will hear, from our scientists, that 
this is straining the enterprise, and it is also discouraging 
new generations.
    So, if you ask me, ``What is the wisdom of science 
administrators worldwide as to: `How do you sustain areas of 
research in cancer,''' or whatever, I think people would say 
that success rates in the 25- or 30-percent range are a minimum 
that you need to sustain research over time so that you can, in 
fact, have a healthy environment.
    Now, in this case--and I published these figures--I'm 
showing you here, in red, the success rate of NIH. If you look, 
historically, it was around 30 percent, if you follow the line. 
Then, in about 2002-2003, it dropped. Why did it drop? Not just 
because we had flat funding. Flat funding did lead to a loss of 
purchasing power. But here is the real story, Senator. More 
scientists are needed to study the complexity of the diseases 
we're dealing with. So, if you look at the curve, the blue 
curve, this is the number of applications we've received at 
NIH. You can see there are more scientists now--there are twice 
as many applications at NIH from twice as many scientists, 
almost, who want to do research. We can't sustain--not even 
one-third, not even 30 percent; we are at about 20 percent 
right now.
    So, that's answer number one. If you don't want to lose 
momentum, that is an objective that you need to look at.
    The second is what you said about: What is the greatest 
impact, and what do we need, to make sure we don't lose? Well, 
first, as you know, we've made some very tough decisions in not 
allowing inflationary increases and focusing, as you've helped 
us this year, on the next generation of scientists. Typically, 
NIH funds 1,500 new scientists a year who get their first major 
grant. Last year, we dropped to 1,400. I want to get back to 
1,500, because if we don't, 10 years from now you won't have 
the researchers to implement the cures that will be discovered 
in the basic research laboratories. So, it's important to 
realize that we need to sustain that. But that cannot be done 
without some compromise or some decrease in other areas.
    So, we have favored, over the past 2 years, what we call 
investigator-initiated research--research project grants to 
individual investigators. At the expense of what? Well, at the 
expense of clinical trials. If you look at our ability to 
conduct clinical trials on patients like yourself, you know we 
want to optimize a protocol for cancer, optimize a protocol for 
prevention of heart disease--prevention of stroke is another 
example--we've had to cut these programs, because they're 
extremely expensive.
    I'll give you an example. Clinical trial costs grow faster 
than inflation, because it's like healthcare, most of the care 
in the clinical trial cost is healthcare. So, it grows at 7-8 
percent. When you have a flat budget, you lose your ability to 
study as many patients. So, that's what we're seeing. This is 
what we're giving up. We're giving up the ability to do 
clinical trials to enable us to change the science and change 
the medicine that we do. So, that's the second answer that I 
think is important here, is that the impact is primarily in our 
ability to translate from the laboratory to the clinic to the 
bedside and to the community what we need to do to prevent 
diseases.
    But I will be happy to provide you very specific answers, 
institute by institute, for the record, Senator.
    [The information follows:]
            reduction in societal burden & health care costs
    The following examples illustrate how research funded by NIH 
institutes lead to reduced societal burden and/or healthcare costs:
National Cancer Institute
            Tamoxifen.--A Preventative Agent for Breast Cancer
    In 2006, breast cancer is estimated to have affected 214,640 
Americans. Since 1978, when Tamoxifen was first approved in the 
treatment of breast cancer, the National Cancer Institute has pursued 
further research to exploit the utility of this hormone receptor-
blocker as a cancer preventative agent. Several studies by NCI and 
others, using over 20,000 women, confirm that tamoxifen can be given to 
prevent Estrogen Receptor-positive (ER-positive) breast cancer, and the 
preventative benefits continue for many years after the women stop 
taking the drug. ER-positive breast cancer accounts for about 60 to 70 
percent of breast cancers. This equates to approximately 128,000 to 
150,000 cases of breast cancer that could be prevented annually. NCI 
previously conducted the STAR trial (Study of Tamoxifen and 
Raloxifene), with nearly 20,000 women, that showed the benefit for 
breast cancer prevention when taking either tamoxifen or raloxifene, 
and for the women taking raloxifene, a lower occurrence of blood clots 
or uterine cancer.
            Cancer Survivorship.--Reducing the Societal Burden
    NCI leads the nation in championing research on the health and 
quality of life of our growing population of cancer survivors, 
currently numbering more than 10 million, up from only 3 million in 
1971. While the ultimate goal of eliminating cancer continues to be our 
long term commitment, the capacity to dramatically reduce the societal 
burden caused by cancer, by increasing survivorship rates, is within 
our immediate reach. Advances in out ability to detect, treat and 
support cancer patients have turned this disease into one that is 
chronic or readily managed for many and curable for increasing numbers.
            HPV Vaccine.--Societal Benefits and Cost Savings
    An important public health milestone was realized when the FDA 
approved a vaccine that prevents infection by HPV 16 and HPV 18, the 
two subtypes of the human papillomavirus responsible for up to 70 
percent of cervical cancer cases worldwide. This approval is a 
watershed moment that highlights the very best of biomedical research: 
the translation of basic and population science into an intervention 
that will save lives.
    Widespread vaccination has the potential to reduce cervical cancer 
deaths around the world by as much as two-thirds (about 250,000 women). 
In addition, the vaccine can reduce the need for medical care, 
biopsies, and invasive procedures associated with the follow-up from 
abnormal Pap tests, thus helping to reduce health care costs. This 
advance also allows NCI to stress the continued importance of cervical 
cancer screening and provides an opportunity to educate the public 
about HPV. By monitoring benefits and risks of HPV vaccination, we can 
optimize the use of HPV vaccines to achieve the greatest health benefit 
for women.
The National Heart, Lung and Blood Institute
    During the past several years, American men and women have 
benefited greatly from continued reductions in morbidity and mortality 
due to cardiovascular disease. The following new findings from NHLBI-
supported research have improved our ability to treat and prevent a 
range of cardiovascular conditions:
  --The ALLHAT revealed that diuretic drugs are at least as effective 
        as newer, more expensive medications in treating hypertension, 
        a major risk factor for coronary heart disease, stroke, and 
        congestive heart failure.
  --The AFFIRM trial established the superiority of a heart-rate 
        control approach to treat atrial fibrillation.
  --An emergency-room-based study demonstrated the utility of magnetic 
        resonance imaging in rapidly diagnosing acute myocardial 
        infarction, thereby enabling timely intervention to restore 
        blood flow to the heart muscle.
  --The PREVENT trial established the efficacy and safety of long-term, 
        low-dose warfarin therapy to prevent the recurrence of blood 
        clots in patients with a history of deep-vein thrombosis and/or 
        pulmonary embolism.
  --A community-based trial found that public access defibrillation 
        performed by trained volunteers increases survival for victims 
        of cardiac arrest.
  --The Sudden Cardiac Death in Heart Failure trial reported that an 
        implanted cardiac defibrillator significantly reduces deaths 
        among patients with moderate-to-severe heart failure.
  --The Prevention of Events with Angiotensin-Converting Enzyme (ACE) 
        Inhibition trial revealed that heart disease patients who are 
        already receiving state-of-the-art therapy do not benefit from 
        additional treatment with ACE inhibitors.
  --The Women's Ischemia Syndrome Evaluation study reported a number of 
        important findings regarding diagnosis and prognosis of chest 
        pain in women.
  --The SHOCK trial concluded that treating heart attack patients who 
        develop life-threatening cardiogenic shock with emergency 
        angioplasty or bypass surgery greatly improves the long-term 
        survival.
  --The first totally implantable permanent artificial heart--the 
        culmination of many years of research efforts by the NHLBI and 
        others--received FDA approval for implantation in certain 
        patients with severe heart failure.
  --The Occluded Artery Trial found that late angioplasty after a heart 
        attack offers no advantage over standard drug therapy.
National Institute of Allergy and Infectious Diseases
            Adult male circumcision reduces HIV transmission
    The NIAID supported two clinical trials in Uganda and Kenya that 
found an approximately 50 percent lower risk of heterosexual 
transmission of HIV among adult men who received a medical circumcision 
compared to men who were not circumcised. These results were announced 
in December 2006.
    The study results indicate that HIV transmission from women to men 
could be lowered, though not eradicated, by increased rates of male 
circumcision.
    The impact of increased access to male circumcision would be most 
pronounced in those areas with low rates of male circumcision and high 
rates of heterosexually transmitted HIV.
    Based on the results of these studies, an international expert 
consultation, convened by the World Health Organization (WHO) and the 
UNAIDS Secretariat, recommended that male circumcision now be 
recognized as an additional important intervention to reduce the risk 
of heterosexually-acquired HIV infection in men.
    Modeling studies suggest that male circumcision in sub-Saharan 
Africa could prevent 5.7 million new cases of HIV infection and 3 
million deaths over 20 years.
            Survival benefits of AIDS treatment
    The NIAID supported a study to quantify the cumulative survival 
benefits of AIDS care in the United States. The results were published 
online in The Journal of Infectious Diseases, in June 2006.
    At least 3 million years of life have been saved in the United 
States as a direct result of care of patients with AIDS.
    The study data demonstrate the dramatic impact that advances in 
anti-retroviral therapy have made on the long-term survival of the most 
vulnerable HIV-infected persons, those who develop AIDS.
    The data also underscore the importance of the global 
implementation of HIV treatment in resource-limited countries and the 
potential for huge survival benefits in those countries.
National Institute of Diabetes and Digestive and Kidney Diseases
            Reducing the Burden of Chronic Kidney Disease and Kidney 
                    Failure
    Diabetes is the leading cause of chronic kidney disease and end-
stage renal disease. Research has shown tight control of blood glucose 
levels can dramatically diminish the development of complications of 
diabetes. With good care, fewer than 10 percent of diabetes patients 
develop kidney failure.
    Kidney disease can be detected earlier by standardized blood tests 
to estimate kidney function and monitoring of urine protein excretion. 
NIH research has shown that drugs (ACE inhibitors and ARBs) that better 
control blood pressure can slow the rate of kidney damage by about 50 
percent. As a result of improved treatment, the number of new dialysis 
patients has stabilized, although troubling racial disparities persist.
    The savings to Medicare for each patient who does not progress from 
chronic kidney disease to end-stage renal disease is estimated to be 
$250,000 per patient. Overall, estimated Federal savings from recent 
improvements in preventing kidney disease is approximately $1 billion 
per year.
National Institute on Deafness and Other Communication Disorders
    Over the last three decades, the NIH's support has played a 
significant and important role in the development of cochlear implant 
(CI).
    NIDCD-supported research demonstrates that the sooner a child with 
severe to profound hearing loss receives a CI, the greater the benefit 
showing age``)appropriate speech perception and language production 
within six to nine months after the CI is turned on.
    NIDCD-supported scientists have found that the benefits of the 
cochlear implant far outweigh its costs in children. A cochlear implant 
costs approximately $60,000 (including the surgery, adjustments, and 
training). In comparison, the services, special education, and 
adaptation related to his or her deafness will cost more than $1 
million if a child is born deaf or becomes deaf before the age of 3.
National Institute on Drug Abuse
    Declining cancer deaths, in part due to decreases in cigarette 
smoking, have resulted from better treatment options for tobacco 
addiction and from effective prevention efforts--buttressed by NIDA-
supported research. For the second year in a row, the CDC reported a 
decline in deaths due to cancer, a remarkable accomplishment stemming 
from research-backed treatments and public education campaigns.
  --NIDA-supported research revealed nicotine as the main addictive 
        component in tobacco, enabling the development of first-line 
        therapies such as nicotine replacement, complemented by 
        behavioral approaches.
  --NIDA-supported education and prevention efforts targeting young 
        people have paid off dramatically in falling rates of teen 
        cigarette smoking, now at the lowest point since 1975, when our 
        Monitoring the Future survey of drug use and attitudes among 
        8th, 10th, and 12th graders was initiated.
  --Since most addiction begins in adolescence and even childhood, 
        these declining smoking rates are likely to lead to continued 
        public health dividends as young cohorts with lower smoking 
        initiation rates age.
National Institute of Child Health and Human Development
    Progesterone Injections Reduce Preterm Delivery.--Currently, 12 
percent of all births are premature and two percent are ``very 
preterm.'' Ten percent of the very premature babies will die and 15 
percent will survive with major disabilities, such as cerebral palsy, 
deafness, blindness or mental retardation. The Institute of Medicine 
estimates that the annual societal economic burden associated with 
preterm birth in the United States was over $26.2 billion in 2005. The 
NICHD's dedication to advancing treatments for preterm birth has led to 
the first successful intervention, which has the potential to reduce 
the associated societal burdens and healthcare costs. Clinicians know 
that women who have previously experienced spontaneous premature labor 
are at greater risk than others to experience it again. Findings from a 
groundbreaking clinical trial showed that treating women, who had a 
previous preterm delivery, with 17 alpha-hydroxyprogesterone caproate 
(17P) reduced, by 34 percent, their risk of another preterm birth. The 
study--conducted within the NICHD's Maternal-Fetal Medicine Units 
Network--also showed that infants, who were born prematurely even 
though their mothers were treated with 17P, had significantly lower 
rates of severe complications. 17P holds tremendous promise for 
reducing preterm birth and life-threatening medical complications in 
infants of high-risk women. The therapy will have even greater public 
health impact when it is extended to other women who are at high risk 
of preterm delivery. Building on this significant public health 
advance, researchers are conducting a study to evaluate progesterone 
therapy in high risk women with twin or triplet pregnancies.
National Institute of Neurological Diseases and Stroke
    One of the first systematic studies of the impact of a publicly 
funded research program on public health and health care costs 
evaluated the costs and benefits of all NINDS phase III clinical trials 
from 1977 to 2000. The total cost of the trials was $335 million. The 
study, published in The Lancet in April 2006, found that over 10 years, 
the trials provided economic benefits that exceeded $15 billion and 
were responsible for 470,000 additional healthy years of life. The 
benefits of the clinical trials program for the entire period covered 
by the study were estimated to be more than $50 billion, far greater 
than the total NINDS budget over that period ($29.5 billion). [Johnston 
et al., The Lancet, 2006, 367:1319-1327].
National Institute of Nursing Research
    Program to Improve Knowledge and Coping Helps Improve Quality of 
Life for Parents of Premature Infants and Reduces Hospital Costs.--
Parents of premature infants often endure high levels of stress, 
anxiety, and depression. NINR-supported investigators tested the 
ability of an educational intervention program for parents, implemented 
early in the Neonatal Intensive Care Unit (NICU), to reduce such 
psychological distress. In what is believed to be first randomized 
controlled trial of its kind, researchers found that parents in the 
program, called Creating Opportunities for Parent Empowerment (COPE), 
demonstrated improved parenting behaviors and reported decreased stress 
levels compared to parents in a control group. Infants of parents in 
the COPE program had a 3.8-day shorter NICU length of stay and a 3.9-
day shorter total hospital length of stay than did comparison infants, 
resulting in decreased hospital costs of about $5,000 per infant.
    Transitional Care Improves Outcomes for Elders After Leaving the 
Hospital.--In a randomized controlled trial, NINR-supported 
investigators evaluated the effectiveness of a transitional care 
program in helping to maintain, after hospital discharge, the health 
and function of elders with heart failure. Elders received a three-
month program managed by Advanced Practice Nurses (APNs) that was 
designed to assist the patients in managing their discharge planning. 
The APNs worked with the patients to identify goals, individualize care 
plans, coordinate care across the different settings from hospital to 
home, and implement a protocol to manage the multiple health issues of 
heart failure patients. A follow-up evaluation at one year showed that 
patients who had received the intervention had a longer time before 
first hospital readmission, along with fewer total rehospitalizations, 
hospital days, and deaths than a control group that continued in 
standard care. Improvements were also noted in patient satisfaction and 
quality of life. The total health care costs over the year-long study 
period were lower by almost $3,500 per patient for those in the APN 
intervention group, when compared to a control group.

    Senator Specter. Thank you very much, Dr. Zerhouni.
    Mr. Chairman, we have, on the floor at the moment, the 
legislation involving the U.S. attorneys who have been asked to 
resign. I am ranking on Judiciary, and I'm going to have to 
excuse myself for a few minutes to go to the floor. We are 
taking up the bill to change the authority of the Attorney 
General to replace U.S. attorneys on an indefinite basis, which 
has caused a lot of controversy. That is being debated right 
now, and I'm going to have to excuse myself to go down there to 
take care of other responsibilities. Senator Feinstein is on 
the floor now, and she was scheduled to speak. I'm scheduled to 
speak after her. But I will be back as soon as I can.
    Thank you.
    Dr. Zerhouni. Thank you, Senator.
    Senator Harkin. Thank you, Senator Specter.

                  IMPACT OF AN ADDITIONAL $1.9 BILLION

    Dr. Zerhouni, just a couple of follow-up questions before 
we turn to our next panel.
    As I said earlier, NIH has lost about 8 percent of its 
funding, in real terms, since the end of that doubling period, 
in 2003, which we saw on the screen also. The advocates from 
different disease groups have asked Congress to get NIH back on 
track by appropriating a 6.7-percent increase for the next 3 
years. By fiscal year 2010, that would equal the amount NIH 
would have attained if it had simply received inflationary 
increases. So, this year, a 6.7-percent increase would equate 
to about $1.9 billion. Just what do you think you could 
accomplish with an increase of $1.9 billion? What would be 
different if we could obtain that $1.9 billion?
    Dr. Zerhouni. Well, again, I think that is--it is key, from 
my standpoint, to understand that in flat budgets we have to 
make tradeoffs, and those tradeoffs tend to affect the ability 
to sustain scientists. So, the ability for us to stay at 
inflation translates directly into our ability to sustain the 
scientific workforce of the United States. For example, NIH 
supports, directly and indirectly, about 326,000 scientists in 
the United States. Every year that we fall behind, in terms of 
inflation, we have to make some difficult choices, which 
typically impact our ability to sustain scientists, who are 
really the key to scientific progress. So, the first thing that 
I think staying even with inflation will do is to allow 
laboratories the resources they need to recruit and retain the 
scientists that are needed to address the very complex issues 
that have come to light, from the scientific standpoint, over 
the past few years.
    I think that the other important aspect of it is that we 
will recover our ability to conduct clinical trials at the rate 
that we need to conduct them. As I said, we've had a flat 
funding of clinical trials since 2003--we have not increased 
the dollars in clinical trials. But, because inflation in 
clinical trials is 6-7 percent, our purchasing power in 
clinical trials is 35 percent less than it was 4 years ago.
    So, that would be probably be one of the priority areas 
that we would like to recover, after recovering what I call the 
optimal success rate. I don't think it's good to have success 
rates that are persistently low. I think we need to make sure 
that the opportunities for new scientists and established 
scientists are recovered.
    So, those are the two things. First, maintaining a viable, 
vibrant workforce--a scientific talent pool of both established 
scientists and new scientists, so that the pipeline continues 
as strong as it has been. Second is to be able to do 
translation, especially when it comes to putting the bench 
discoveries to practice.

                              COMMON FUND

    Senator Harkin. The NIH Reform Act that we passed last year 
puts a big emphasis on the common fund----
    Dr. Zerhouni. Yes, sir.
    Senator Harkin [continuing]. Again, to support trans-NIH 
initiatives that benefit all areas of disease research. A 
couple-three, things. One, again, can you just spend a couple 
minutes describing what you hope to attain--accomplish that 
fund, what are some of the examples of the kind of initiatives 
that would be funded through this effort. Last, how about 
initiatives for particular diseases? Some diseases cross many 
institutes and centers. Could they be funded through the common 
fund?
    Dr. Zerhouni. Sir, the common fund is about 1.5 percent of 
the NIH budget today. It really came from the concept of 
having--as I said, institutes are extremely good at fulfilling 
their missions; however, science changes, and often there are 
areas that fall between the cracks, that you need to sustain, 
especially when it comes to high-risk, high-impact research. 
So, we want to sustain our ability, despite tight budget times, 
to fund innovative ideas and innovative scientists. That is a 
role that I see for the Common Fund.
    Second, emerging areas of science that are not necessarily 
in the priority of any one institute. A good example is 
nanotechnology. When I became Director the total investment of 
NIH in nanotechnology was $50 million. There wasn't an 
institute that really focused on that. The new institute, the 
National Institute of Bioimaging and Bioengineering, was just 
created, and that's their mission, but they were too new, and 
clearly you needed to make a large advance across the board. 
That's when we use common fund monies, to sort of launch this 
area.
    Another example is what we call molecular libraries. 
Scientists told us that they needed to have access to more 
molecules to see if they could understand better the diseases 
in their own assays. Well, that was not available to NIH-funded 
scientists. So, the--no institute really has either the mission 
or the interest or the scope to fund that. So, we funded it. 
But what is really important, Senator, is that the common fund 
is like a glue fund. In other words, it's the--you know, NIH is 
like 27 fingers; the common fund is the palm, is the 
coordination, the strategizing of the future of science, 
funding areas that wouldn't be funded otherwise. It is really 
to incubate novel ideas. For example, you could have seen the 
common fund being used in emerging areas of science, like stem 
cells, at the beginning, or RNA interference. RNA interference 
is a new mechanism that was discovered in 1998. The work 
received the Nobel Prize in 2006. When I became Director of the 
NIH, I was very keen on finding monies to support that area of 
research. It was emerging at the time. So, that's the kind of 
uses that you would want to see for the common fund, uses that 
are at the frontier of science, serve all institutes, that are 
not specifically for something that will last forever, but it's 
just like the kickoff fund, if you will. Five years of funding, 
10 years of funding, to get a new area of science started.
    Think of the human genome. In 1991--I think you were on the 
committee at the time----
    Senator Harkin. Chairman.
    Dr. Zerhouni [continuing]. You were the chairman of the 
Committee--the then-Director of NIH came to you and asked you, 
as an exceptional measure, to fund the human genome. The human 
genome was going to be done at the Department of Energy, 
because they had an Opportunity Fund. NIH did not have that. 
So, when I talked to my predecessors, Dr. Varmus, Dr. 
Wyngaarden at that time, they all said the one thing that is 
needed at NIH is some sort of a common fund for common purposes 
that emerge unpredictably that we need to respond to. That 
could apply to a public health emergency, no doubt about it. 
But, again, it's a revolving venture fund to make the agency 
nimble, reactive, not to serve specific interests, but to serve 
the agency as a whole. I don't know if I'm making myself clear.
    Senator Harkin. Can particular diseases, then, be funded 
through this, or not?
    Dr. Zerhouni. I would rather not. I would think that the 
particular diseases that need to be funded should be funded 
through the institutes that have the missions----
    Senator Harkin. But some of these----
    Dr. Zerhouni [continuing]. To serve that.
    Senator Harkin [continuing]. Diseases cross a lot of 
different institutes. That's the problem.
    Dr. Zerhouni. So, what we do in that case, when there are 
diseases that are relevant to the mission of multiple 
institutes, we have other mechanism, where we encourage 
institutes to work together. For example, we've had an obesity 
research plan. It's not funded through the common fund. It's 
the responsibility of different programs in the institutes, so 
that what we do there is, we encourage the institutes to work 
together. For example, the strategic plan for obesity research 
was published and involves over 19 institutes. The neuroscience 
blueprint is another example of addressing diseases that need 
to be served by the institutes whose mission is to serve those 
diseases in their various dimensions.
    Unless it's an area that really requires across-the-board 
stimulus--remember, no initiative in the common fund stays for 
more than 5 to 10 years, max. That is the idea of the common 
fund. It's not to replace, or a new source of funding for 
special diseases that don't find a home somewhere else. Very 
important, I think, to keep that in mind.

                             PUBLIC ACCESS

    Senator Harkin. I appreciate that.
    One last thing, we have to move on to the next panel. It 
concerns public access to NIH-funded research. You have 
proposed that NIH-funded researchers should have to submit 
their final peer-reviewed papers to an NIH database after 
they're accepted by scientific journals, and that these papers 
should be made available through the database within 12 months 
after their publication in the journals. What's the scientific 
value of increasing public access to this research, as you 
propose? Why 12 months? Why not 6 months? You've asked Congress 
to require NIH-funded researchers to adhere to this policy; why 
do we have to do it? Can't you do that on--you know, can't you 
simply require that through NIH? Why do we have to do it?
    Dr. Zerhouni. First of all, I think it's important, in the 
information age that we're in, to make sure that publicly 
funded research be available in a database that we can search 
and connect to all the many other databases that are available 
to us. It is also important not to damage peer review. But it 
is important to realize that NIH needs to have a--the ability 
to do that without damaging journals. That's why 12 months, 
that's why not 6 months. Because most journals will say that 6 
month--for 78 percent of journals, 6 months might be okay, but 
for others that are not published as frequently, it's not--it 
will damage their ability to sustain themselves. So, I think we 
need to be more flexible.
    What I think we can't be flexible on is the mandatory 
nature. We've tried voluntary. I have data about how this is 
working. I mean, you can see here, for example, that the 
publications that are being submitted represent less than 10-15 
percent--the compliance is the red number, the red bar--the 
compliance is not as high as it should be. I think we should--
we need to make this a condition of Federal grant funding, and 
that's why we need you to express the wish of Congress to do 
that, as easily as we can.
    So, my position is, a mandatory policy seems to be the one 
that will be necessary for us to achieve our goals. We've tried 
voluntary. It doesn't seem to be working as well. I think we 
need to be flexible on the time. I don't think that we should 
force a date certain, because it would harm some journals and 
not others.
    Senator Harkin. That's really all the questions I have, Dr. 
Zerhouni. Is there any last thing that we didn't bring up that 
you'd want to get out before I----
    Dr. Zerhouni. Again, I think that what I'd like to say is 
how appreciative of you and Senator Specter and the rest of the 
subcommittee I am. I think that it is key that we continue the 
momentum.
    I have been in--I wanted to give you a perspective about 
international competition. I just came back from Europe. They 
have decided to focus on life sciences, and accelerate their 
investment in life sciences. They've just created a new NIH-
like institution in Europe, $57 billion of funding in 5 years. 
I've been to China; there's a tripling of the research budget. 
I've been to India; and there is also an increase in research. 
There are strong attempts to re-recruit back from the United 
States. I think we definitely need to understand the strategic 
importance of NIH. I think you do, but I just want to be on the 
record to say that nothing is more important than sustaining 
our investment in science and medical research.
    Thank you.
    Senator Harkin. Well, Dr. Zerhouni, thank you very much for 
your leadership, and also, again, I want to thank you for your 
statement concerning embryonic stem cells. Hopefully, we're 
going to move ahead on that, this year, put it behind us, and 
get about funding this much-needed area of research in our 
society. So, I thank you for your statement today.
    Well, Dr. Zerhouni, now, we're going to move to our next 
panel. Respectful of your time, if you'd like to stay, and 
maybe there might be some questions we might have afterward, 
but I----
    Dr. Zerhouni. I'd be happy to stay.
    Senator Harkin [continuing]. It's not part of the deal, so 
if you can stay, we'd appreciate it; if not, then that's fine.
    Dr. Zerhouni. Thank you, Mr. Chairman. I'll be happy to 
stay.
    Senator Harkin. Well, I appreciate that very much, Dr. 
Zerhouni.
    Let's bring our next panel up: Dr. Iverson, Dr. Brugge, Dr. 
Siliciano, and Dr. Strittmatter.
    Again, for all of you, welcome to the subcommittee. All of 
your statements will be made a part of the record in their 
entirety. I'd ask, if you could sum it up in 5 minutes, your 
major point, I'd appreciate that. We can elucidate more of it 
in our questions-and-answer period.
    So, I'll go in the order in which I called you. Dr. Brent 
Iverson, distinguished teaching professor of organic chemistry 
and biochemistry at the University of Texas at Austin, received 
his bachelor's of science degree from Stanford and his Ph.D. 
from the California Institute of Technology.
    Dr. Iverson, welcome to the committee, and please proceed.
STATEMENT OF BRENT IVERSON, Ph.D., UNIVERSITY 
            DISTINGUISHED TEACHING PROFESSOR OF ORGANIC 
            CHEMISTRY AND BIOCHEMISTRY, THE UNIVERSITY 
            OF TEXAS AT AUSTIN, AUSTIN, TEXAS
    Dr. Iverson. Thank you, Mr. Harkin.
    I am here representing NIH-funded scientists at research 
universities. I was an undergraduate business major at Stanford 
until I worked in Professor Jim Coleman's laboratory in 
chemistry research. It was an NIH-funded research laboratory. 
My undergraduate research experience charted the course that 
directly led to my scientific career.
    My research spans the interface of organic chemistry and 
molecular biology on the basic science and of the biomedical 
research spectrum. I am an inventor on 20 patents, many of 
which are being used by companies right now.
    I would like to make three points concerning the importance 
of growing the NIH budget.
    The first point concerns being able to take full advantage 
of what the doubling allowed us to initiate. In my own lab, the 
increased funding provided by the doubling allowed my 
collaborators and I to develop a powerful new method we call 
APEx that allows us to enhance the activity of antibodies. 
Antibodies are the hottest segment of the pharmaceutical 
industry today, with over 20 now approved, such as Avastin and 
Herceptin, for treating colon and breast cancer, and Remicade 
and Humira for treating rheumatoid arthritis and Crohn's 
disease.
    Antibody drugs are so-called targeted therapies because 
they're capable of seeking out and attacking only their 
intended disease targets, with remarkable precision; sort of 
the smart-bomb approach for drugs. The result is a much more 
concentrated therapy, one that limits many of the serious side 
effects of traditional approaches.
    Our APEx allows us to make existing antibodies more 
powerful by a factor of 10 or 100 or more. For example, we 
started with an antibody against anthrax that could delay, but 
not prevent death, in animals exposed to live anthrax spores. 
After making the original anthrax antibody about 20 times more 
potent, our engineered antibody prevented illness and cured 
animals treated with the same lethal dose of live anthrax 
spores. That antibody is being pursued commercially by Elusys, 
Incorporated, of New Jersey, and will hopefully become a 
stockpiled countermeasure that should be effective past the 
point at which Cipro alone works.
    With APEx, we are starting--we are ready to start working 
on engineered antibodies that attack a variety of diseases, 
such as allergies, inflammatory diseases, and cancer. I believe 
there are many, many researchers like me poised to make a 
difference with all the tools now in place, but limited by a 
flat budget. This is not the time to pull back.
    My second point concerns basic science breakthroughs. Flat 
funding, as we have now, has the effect of making grant funding 
decisions overly conservative. Let me bottom-line it for you. 
There is currently too little support for innovative, risk-
taking, basic research without new money, because the money we 
are given largely goes to fund the many worthy older ideas. 
Less than 10 percent of the grants in my research area receive 
money each round of consideration. Less than 10 percent. There 
is simply not enough money left over for new ideas that are not 
yet proven.
    In other words, there is not enough money right now for new 
ideas that could establish new paradigms or provide new 
opportunities for new therapies, exactly the kind of basic 
science research that cannot be done in the commercial sector.
    For example, I want to draw your attention to the green 
panel in our report. This is a molecule from my lab that binds 
to DNA in an entirely new way. It was discovered in the context 
of an exploratory project designed to move in an entirely 
different direction, yet it could someday form the basis for a 
therapy of the target's DNA directly as a point of interaction.
    Conservative funding decisions mean there is also not 
enough money to fund those scientists who have not yet had the 
opportunity to prove themselves; namely, new faculty members. 
Further, our current graduate students are being dissuaded from 
an academic research career by the difficulty young faculty are 
having in receiving funding right now.
    I would like to finish by describing my concerns about 
science education. I hope all of you understand that the 
product of NIH funding is not only the research itself, but, 
additionally, the training of students. For the U.S. 
pharmaceutical and biotech industries, NIH is, by far, the most 
important sponsor of projects that result in scientist 
training. Talk about strategic economic leveraging.
    I generally accept three to four new Ph.D. students in my 
laboratory every year. With the significantly reduced chance of 
getting a grant funded, I am forced to take proportionately 
fewer graduate students. In fact, I am not accepting a single 
new graduate student this year in my antibody engineering 
laboratory.
    Tight funding impacts undergraduate research opportunities, 
as well. I have had over 100 undergraduates work in my lab. 
Across our campus, around 1,000 undergraduates will take part 
in cutting-edge scientific research, many in state-of-the-art 
labs with NIH funding. Fewer research grants means fewer 
opportunities for undergraduate researchers.

                           PREPARED STATEMENT

    Together, I view this as a very ominous combination. Not 
enough money to take advantage of recent advances, a 
conservative research environment that discourages risk-taking, 
and not enough support for state-of-the-art science education. 
I am convinced that a lack of new money today will have a 
crippling effect on our global competitiveness, and will limit 
medical breakthroughs for decades.
    Thank you.
    [The statement follows:]

                Prepared Statement of Dr. Brent Iverson

    My name is Dr. Brent Iverson. I am a Distinguished Teaching 
Professor and the Raymer Professor of Chemistry and Biochemistry at the 
University of Texas at Austin. I am here representing NIH funded 
scientists at research universities, both public and private. I was an 
undergraduate business major at Stanford University until I worked in 
Professor Jim Collman's chemistry research laboratory. My undergraduate 
research experience in that NIH-funded lab charted the course that 
directly led to my scientific career.
    Today, I want to tell you about NIH funding from my individual 
perspective, to help put a face on the budget numbers. My research 
spans the interface of organic chemistry and molecular biology, on the 
basic science end of the medical research spectrum. I have well over 
100 publications, many in the most prestigious scientific journals. I 
hold 20 current or pending patents, most of which are licensed and are 
being used by companies across the country.
    I would like to make three points concerning the importance of 
growing the NIH budget. The first point concerns being able to take 
full advantage of what the budget doubling allowed us to start. In my 
own lab, the increased funding provided by the doubling allowed the 
development of a powerful new method we call APEx that allows us to 
engineer better antibodies.
    Antibodies are the hottest segment of the pharmaceutical industry 
today, with over 20 now approved for the treatment of diseases such as 
cancer (ex. Avastin and Herceptin, for treating colon and breast 
cancer, respectively) and rheumatoid arthritis (ex. Humira). Antibodies 
are even being pursued as a new approach to treating infectious 
diseases. Antibody drugs represent the new generation of so-called 
targeted therapies, because they are capable of seeking out and 
attacking only their intended disease targets with remarkable 
precision. The result is a much more concentrated therapy, one that 
avoids many of the serious side-effects of more traditional approaches 
such as the standard chemotherapeutic agents used to fight cancer.
    Our APEx method allows us to take existing antibodies and make them 
more powerful by factors of 10 or even 100 or more. This can often make 
the difference between an effective or ineffective antibody treatment. 
For example, we started with an antibody against anthrax that could 
delay but not prevent death in animals exposed to live anthrax spores. 
After making the original anthrax antibody about 20 times better, our 
engineered antibody prevented illness and even cured animals treated 
with the same dose of live anthrax spores. That antibody is being 
pursued commercially and may soon become a stockpiled countermeasure.
    With APEx developed, we need continued strong funding to take full 
advantage of it. We are ready to start working on engineered antibodies 
that attack a variety of disorders such as allergies, inflammatory 
diseases, and cancer. I am very worried that in the current funding 
climate, our ability to pursue these diseases is going to be severely 
limited. You can only imagine my frustration at working so hard to 
develop the means of making a difference, then having limited support 
to apply it broadly.
    I would like to make a second important point, this one concerning 
basic science breakthroughs. Tight funding as we currently have now has 
the effect of making grant funding decisions overly conservative. I 
have been on many NIH funding panels and have seen this phenomenon in 
action. Right now, only about 10 percent of the grants in my research 
area receive money, so the panels must choose the ``can't miss, sure 
things'' that represent the obvious next steps of research. It is not 
that the panels are overly conservative, it is just that no panel can 
reject these proposals because they will almost certainly lead to 
advances based on the strong scientific foundation upon which they are 
built. But what about new ideas that are not proven yet? In other 
words, the ideas that come out of nowhere, establish new paradigms and 
change the way we think. With such a limited number of grants 
supported, there is no money in the system for us to work on more 
speculative projects, ones closer to the leading edge of knowledge. 
There is also not enough money to fund those scientists who have not 
yet had the opportunity to generate extensive preliminary results, 
namely new faculty members.
    Scientific breakthroughs rarely come from a research effort aimed 
at the ``can't miss obvious next step''. In my experience, our 
breakthroughs have come when we least expected it while we were 
exploring beyond the boundary of what we understood well. For example, 
I want to draw your attention to the cover of the brochure you have 
been given today. There is an outline of a complicated molecule in the 
green panel. It is actually a molecule from my laboratory that binds to 
a large, specific sequence of DNA using an entirely new type of 
interaction we have named threading polyintercalation. Our molecule is 
the first reported to bind to the DNA double helix with a topology that 
can be described as being similar to how a snake might climb a ladder.
    This new approach came from a highly speculative project in my lab 
intended to make an artificial protein, but once we started analyzing 
the behavior of our molecules, we realized that what we were doing was 
also applicable to targeting DNA. Although not yet ready for commercial 
application, imagine a new class of drugs of the future that target the 
DNA sequences of viruses, bacteria, or cancer cells directly. Talk 
about getting to the heart of the matter!
    Without increased funding, our ability to explore boundaries such 
as these and make startling breakthroughs is going to be severely 
limited. True breakthroughs that move science in new directions often 
take years to turn into a practical new therapy and only occur when 
scientists are given the freedom to take scientific risks. I am deeply 
concerned that a lack of money today to explore beyond conservative 
boundaries will have a crippling effect on medical breakthroughs that 
will be felt for decades.
    As a corollary to this, I am also concerned that the current lack 
of funding support will take a heavy toll on young scientists in two 
ways. The most direct is that they will not receive enough funding to 
launch their careers because there is only enough for the established 
scientists. As a more indirect effect, I am worried that the bleak 
funding picture will dissuade the best and brightest from even pursuing 
a career in academic scientific research.
    I would like to finish by describing my concern about science 
education. I hope all of you understand that the product of NIH 
research funding to University researchers is not only the research 
itself, but additionally, the training of students. It is a very simple 
equation. Limited funding for research now means fewer trained 
scientists for the future and consequently fewer research breakthroughs 
for years to come. As a result, I am very concerned that our place as 
the world leader in medical research is not secure.
    I generally accept 3-4 new PhD students in my laboratory every 
year. My former students now work in academics as professors/
researchers or in many companies around the country. With a 
significantly reduced chance of getting a grant funded, I am forced to 
take proportionately fewer graduate students. In fact, I am not 
accepting a single new graduate student this current year in the 
antibody engineering lab. The bottom line is that limited funding means 
we are also limiting the number of students being trained, and I 
believe our country needs more, not fewer, highly trained scientists to 
maintain a healthy technology-based economy.
    Finally, being on the campus of one of the largest undergraduate 
institutions in the country, I am acutely aware that NIH research 
funding has a tremendous impact on large numbers of undergraduates. I 
have had over 100 undergraduates work in my lab. Across our campus, 
around 1000 undergraduates will take part in state-of-the-art 
scientific research, most of it in state-of-the-art labs with NIH 
funding. The positive impact of this is almost incalculable. Most of 
these individuals will not go on to become scientists like I did, but 
they will be able to articulate to the rest of society what science is, 
and what research means for our country. With every study pointing to 
the frightening inadequacy of scientific education across our 
population, a rare piece of good news is undergraduate research. We 
need leaders in all segments of society who understand science and can 
make appropriate choices as we chart the increasingly technological 
future of our country and our world. Again, it is a simple equation. 
Not enough money for the labs means proportionally fewer undergraduate 
as well as graduate student research opportunities across the country.
    As a University researcher in the prime of my career, I need to see 
enough money in the NIH budget so that I can take full advantage of 
what the doubling allowed me to create. There needs to be enough money 
in the system to help provide an environment that allows risk taking, 
thus making scientific breakthroughs more likely and allowing young 
scientists the opportunity to launch their careers. We also need budget 
growth to continue the essential scientific training of students 
ranging from undergraduates to PhD's. All of this is essential if the 
United States is to remain the world leader in both academic and 
commercial medical research.

    Senator Harkin. Dr. Iverson, thank you very much for that 
statement.
    Now we turn to Dr. Joan. I hope I pronounce that right--
Brugge?
    Dr. Brugge. Perfect.
    Senator Harkin. The chair of the Department of Cell Biology 
at Harvard Medical School. She received her B.A. in biology 
from Northwestern, and her Ph.D. in virology from Baylor 
College of Medicine.
    Dr. Brugge, please proceed.

STATEMENT OF JOAN S. BRUGGE, Ph.D., CHAIR, DEPARTMENT 
            OF CELL BIOLOGY, HARVARD MEDICAL SCHOOL, 
            BOSTON, MASSACHUSETTS
    Dr. Brugge. So, first I'd like to thank Chairman Harkin and 
ranking member Specter and the members of the subcommittee for 
this opportunity to tell you about some of the real remarkable 
advances in biomedical research that have been made possible by 
your strong support for NIH.
    I also hope to convey, as well, my personal excitement for 
the incredible potential that's still to be realized in my 
field of cancer research. Unfortunately, this enthusiasm is 
dampened by my profound concerns that the past 4 years of flat 
funding has significantly compromised our ability to fully 
realize this potential.
    When I was a sophomore math major at Northwestern 
University, my sister was diagnosed with a malignant brain 
tumor. This event, and her subsequent death, redirected me 
towards a career in cancer research. Most of my career has been 
spent in universities and medical schools, but, before becoming 
a professor and then chair at Harvard, I served as the founding 
scientific director of a biotech company in Boston, and that--
the industry experience has significantly shaped my 
understanding of the critical issues that are involved in 
translating basic discoveries into clinical therapies for 
patients.
    So, as you're probably aware, in the early 1970s, when I 
entered cancer research, it was actually a very heady time for 
science. Many of us expected, on the basis of the success of 
the polio vaccine and the congressionally mandated war on 
cancer, that we would very soon have a cure for this horrible 
disease, but we very rapidly learned that cancer is not just 
caused by a single agent, and it's not just a single disease, 
as Mr.--or Senator Specter pointed out earlier. We now know 
that there are hundreds of different forms of cancer. In fact, 
each tumor from an individual patient contains a unique set of 
genetic changes. So, this unexpected complexity, which is 
really unique to cancer, presented a huge challenge in the 
development of effective treatments.
    So, actually, over the last decade there has been an 
enormously rapid pace of discoveries on the causes of cancer, 
but it's really not until recently that I have felt real 
confidence that the year--the congressional investment in 
cancer research was going to pay off much more directly to 
patients.
    So, at this time, our fundamental understanding of the 
causes of this disease, and the molecular underpinnings, have 
led to substantially new and revolutionary new approaches to 
treating cancer. So, as you're probably aware, most cancer 
therapies that are used today are--very nonspecifically target 
any kind of proliferating cell. So, that's why there are 
significant toxicities to blood cells and immune cells, to your 
hair, digestive system. But the recently developed cancer 
therapies are aimed very specifically at what we now understand 
to be the very--the unique vulnerabilities of tumors, the so-
called Achilles' heel of tumor cells. This is leading to much 
more effective and less toxic therapies.
    You're probably familiar with some of the many examples of 
effective drug treatments that are targeting these specific 
subsets of tumors with specific molecular defects. These 
successes are actually providing a blueprint for application to 
many more types of cancer.
    So, I think what we now foresee that is in the near future, 
there--we'll have customized therapies for cancer, that will be 
based on the specific molecular diagnosis of a tumor. So, this 
is already being done in breast cancer, where each tumor tissue 
is evaluated for specific markers that will predict whether a 
specific drug will work or the specific drug will not work. 
Results are really dramatic, so these drugs are adding years to 
the lives of patients--and the most aggressive forms of blood 
cancer--sorry--breast cancer. So, it's an example of the 
precision medicine that Dr. Zerhouni introduced.
    So, these successes are really just the tip of the iceberg. 
Underneath the surfaces, there's a real foundation for much 
more rapid pace of breakthroughs in cancer detection and 
treatment based on the research investment in the past.
    So, this, then, brings me to my profound concerns regarding 
the state of NIH funding today. Four years of flat funding have 
had a very significant impact on the trajectory of cancer 
research. We are losing momentum and the dedicated careers that 
were fueled by the previous investments. We're damaging the 
research capacity, and this will certainly delay relief from 
the cancer burden.
    So, you've seen the statistics indicating a 20-percent 
success rate of grant applications. Let me just give you 
appreciation for what those mean--those numbers mean to the 
team of scientists in the research labs.
    While the reported success rate is 20 percent, this number 
actually represents the success of either first, second, or 
third submission of a grant, or the eventual success. So, 
what--the actual first rate of--the success rate on first 
submissions is actually half of that, around 10 or 12 percent. 
So, basically, 90 percent of the scientists that apply for 
grants are not receiving them the first time around. So, what 
does that mean? That means there's at least a lapse in funding, 
and perhaps the loss of the grant. So, what happens when a lab 
director fails to get a grant? The--a lapse in funding forces 
the lab to cut back, they have to let staff go, and now your 
efforts are redirected on alternate funding and resubmission of 
the grant, instead of moving forward. So, this not only 
forestalls progress, but it also creates an atmosphere of 
insecurity and anxiety, and that actually precludes conduct of 
a creative, innovative exploration.
    Once the scientist does secure funding after this lapse, 
this requires retrenching and retraining, and--basically, a 
loss of continuity is probably the most serious problems for a 
scientist.
    Scientists at all levels are being affected, not just at 
the higher--not just at the lower echelons, but even at 
Harvard. There's two to four investigators in every department 
that I surveyed, that has had a significant lapse or loss of 
grants, that were rated as outstanding by the peer-review 
group.
    The other thing I think it's important to understand is 
that even if one is successful in getting a grant over one of 
these three submissions, each grant is getting cut between 20 
to 30 percent. So, at NCI in the last year, there was a cut of 
24 to 29 percent. So, for instance, a grant that's $200,000 
will now get $140,000. That will barely cover the salary of the 
principal investigator. So, we're now faced with funding labs 
at levels that are 7--at levels that we have 7 to 10 years ago, 
just--with--and that's not--and so, we have to deal with 
inflation at the same time, a 30-percent increase in mandated 
stipends, and also the much higher cost of new technologies for 
state-of-the-art research. So, as a result, every grant is 
severely underfunded and--for achieving the approved goals--and 
scientists are starving.
    As Brent mentioned, the frustration and anxiety of lab 
directors is not get--is not going unnoticed by trainees. Young 
scientists are looking for other venues to exercise their 
talents where their long investment and training won't be 
jeopardized by the lottery, even at the highest--even for the 
most outstanding grants. This has profound implications for 
science of the future, since we won't be able to fill in the 
gaps of that lost generation.
    Then, last, I'd just like to make the point that we really 
can't afford to stand still, because the demographics are 
against us. As you're fully aware, in 2030 there will be twice 
as many Americans over 65 compared to the number today. So, 
given that there's a 10-times higher incidence of cancer in 
individuals over 65, there's going to be a virtual tsunami of 
cancer. This is staggering not only with respect to the 
personal suffering, but also the cost consequences of the 
cancer burden on our economy.
    So, I feel that investment now could have profound savings 
later. According to one report, a 1-percent decrease in cancer 
mortality is reported to be worth $500 billion to our economy.
    So, as Geoff Wahl, who's president of American Association 
of Cancer Research, has pointed out, unlike a real tsunami, 
which we have no time to prepare for, we are well aware of the 
impending crisis, and congressional investment in research has 
positioned us to make much more rapid progress in translating 
basic discoveries into the diagnosis, treatment, and eventually 
prevention of cancer. We really owe it to the public to 
capitalize on these investments.
    I'd just like to finish, then, by making the point that 
it's through your foresight, and those of other members of the 
committee, that the public has generously provided a start 
towards eradicating one of the scourges of human health. But 
now, just as these new therapies, based on our molecular and 
cellular understanding of cancer, is emerging, the opportunity 
to expand them to other types of cancer, to build on them, and 
to provide for a future of more discoveries, has idled. Dr. 
Neiderhuber shared with me some slides that he just presented 
to his Board of Scientific Advisors, and there's this long 
list--long set of--or numerous slides showing missed 
opportunities he's unable to fund. This included a list of very 
important projects, resource development, and clinical trials 
that were canceled because of this cutback. This is very 
distressing. These cutbacks are going to delay benefit to the 
public.

                           PREPARED STATEMENT

    So, we can't retreat now that the--our infrastructure is in 
place, and we're really mobilized to launch a full attack on 
this disease. So, for the sake of the American people, please 
find a political route to keep progress against cancer at a 
sustainable pace. The research findings are clear, there is a 
path to major advances. Help us get these advances to the 
public and fulfill the promises of the best in scientific 
research.
    Thank you.
    [The statement follows:]

                Prepared Statement of Dr. Joan S. Brugge

    First, let me thank Chairman Harkin, ranking member Specter, and 
members of the committee for this opportunity to report to you some 
remarkable advances that have occurred in biomedical research because 
of your strong support for NIH. I hope that I can convey as well my 
personal excitement for the incredible potential still to be realized 
in my own field of cancer research. Unfortunately, this enthusiasm is 
dampened by profound concerns that the four years of flat funding has 
compromised significantly our ability to fully realize this potential.
    When I was a sophomore math major at Northwestern University, my 
sister was diagnosed with a malignant brain tumor. This event and her 
subsequent death redirected me towards a career in cancer research. 
Most of my career has been spent in universities and medical schools. 
However, for five years before I came to Harvard Medical School, I 
served as the Scientific Director of a biotechnology company focused on 
cancer and other diseases. My industry experience significantly shaped 
my understanding of issues critical to the translation of scientific 
discoveries into therapies for patients. It taught me among other 
things, that though the path to treatment can be arduous, today the 
path between basic discovery and successful drugsalso can be remarkably 
short.
    The early 70's, when I entered cancer research, was a heady time in 
science. Many of us expected, based in part on the success of the polio 
vaccine and the Congressionally mandated War on Cancer, that we would 
soon have a cure for this horrible disease. However, it soon became 
evident that cancer, unlike polio, is not a single disease with a 
single cause. There are hundreds of different forms and, indeed, tumors 
from individual cancer patients carry unique sets of genetic changes. 
This unexpected complexity--unique to cancer--precluded rapid 
development of a single vaccine or simple cure.
    Though we certainly underestimated the complexity of cancer, the 
Congressional investment in cancer research is now beginning to pay 
off. We have made enormous progress in understanding the cause of this 
disease and its molecular underpinnings. This fundamental information 
has led to revolutionary approaches to treatment, aimed specifically at 
the unique vulnerabilities of specific tumors; we now know how to 
target a tumor's genetic or molecular Achilles' heel. In addition, new 
imaging modalities and biomarkers provide the potential to identify 
tumors at early stages when treatments are most effective.
    Today, I feel a new confidence that we are poised to make rapid 
progress in developing effective and less toxic treatments for the 
myriad different cancers. This confidence is based on initial evidence 
of success. We now have multiple examples of effective treatments that 
target the molecular alterations of specific subsets of tumors (such as 
Tarceva for a subset of lung tumors, Gleevec for chronic myelogenous 
leukemia, and Tykerb, approved just a week ago for treatment of certain 
breast cancers). These successes provide a blueprint for the 
development of treatments for many more types of cancer.
    Cancer treatment in the future will involve a molecular diagnosis 
of each tumor, followed by customized therapies. Already this is being 
done for breast cancer, in which tumor tissues are probed for several 
markers that predict which tumors will respond to specific drugs (like 
Tykerb, Herceptin, or estrogen antagonists) and which will not. The 
results are dramatic, adding years to the lives of many patients with 
the most aggressive forms of breast cancer, and sparing patients of 
treatments that offer no promise of efficacy. For the first time, we 
are seeing a decrease in deaths associated with cancer. The tip of the 
iceberg is visible, underneath lies the foundation for a rapid pace of 
breakthroughs in cancer detection and treatment based on the research 
investment in the past.
    We cannot afford to stand still--the demographics are against us. 
There is an impending increase in cancer due to the baby boomers aging 
into their cancer-prone years, which has been referred to as an 
impending tsunami. You are all keenly aware of the ramifications for 
government of Medicare entitlements associated with this surge in 
cancer. But unlike a real tsunami, which comes unexpectedly with no 
time for preparation, we are well aware of this impending crisis. And 
We know that the Congressional investment in basic and cancer-focused 
research has positioned the cancer research community to make more 
rapid progress in translating basic discoveries into the diagnosis, 
treatment, and eventually, prevention of cancer. We owe it to the 
public to capitalize on these investments; failure to maintain the pace 
of advancement towards reducing the suffering of cancer is not an 
option the American people should support or will support. We are all 
in this together.
    This brings me to my profound concerns regarding the state of NIH 
funding today. Four years of flat funding have had a devastating impact 
on the trajectory of cancer research. We are losing the momentum and 
the dedicated careers that were fueled by the previous federal 
investments. We are now damaging the research infrastructure, and this 
will certainly delay relief from the cancer burden.
    While you have seen the statistics regarding grant awards presented 
by Dr. Zerhouni and others at NIH and are aware of the inflationary 
erosion of our buying power, the mere numbers mask the profound effects 
on the research community. I would like to give you an appreciation for 
what these numbers mean to the cancer research community, which is 
emblematic of the whole research enterprise. While the eventual success 
rate of grants is 20 percent, this number reflects success of either 
the first, second, or third submission of a grant. The success rate of 
the first submissions is now about half of this; thus the vast majority 
of scientists are subjected to a lapse in funding and the negative 
consequences of this. Not only can a lapse in funding force labs to cut 
back, let staff go, and redirect efforts to finding alternative funding 
and resubmission, it creates an environment of insecurity and anxiety 
that is anathema to the conduct of creative, innovative exploration. 
Recovery after a 6-12 month funding gap requires retrenching and 
retraining of new staff. Many leads will never be followed up. Loss of 
continuity is one of the most serious problems for a scientist. For new 
investigators, repeated failure to launch their research program is 
also demoralizing, and discourages taking original and risky paths.
    Researchers at all levels are affected--those beginning their 
careers and senior investigators with long and sustained track records 
of major discoveries. For example, multiple colleagues at Harvard 
Medical School who are leaders in their field with outstanding 
accomplishments, are suffering lapses in funding or losing grants that 
received priority scores in the 10-20 percentile range. Peer review is 
too imprecise to distinguish differences in the quality of the grants 
in this tight range.
    Second, in order for the success rate of grants to hit the mandated 
target number of grants, NIH has resorted to cutting grant size 
dramatically--at NCI, 24-29 percent (2006). Aggravating this situation 
are reductions in buying power due to inflation and the 30 percent 
increase in mandated stipends for graduate students and postdoctoral 
fellows over the past seven years (an increase that we applaud). Lab 
directors are faced with carrying their labs at funding levels 
equivalent to those 7-10 year years ago, at a time when there is a 
significant increase in cost of the new technologies required for 
state-of-the-art research. As a result, almost every grant is severely 
under-funded for achieving the approved goals, and scientists are 
starving for resources.
    The frustration and anxiety of lab directors is not going unnoticed 
by trainees, and many young scientists are looking for other venues to 
exercise their talents, ones where their long training investment will 
not be jeopardized by this lottery in NIH grant review. This has major 
implications for the science of tomorrow, since we will not be able to 
fill in the gaps of this lost generation.
    I would like to reiterate the long-term implications of the current 
research budget shortfall on the economy. Cancer incidence for those 65 
and older is 10 times greater than for those under 65, and the death 
rate is 16 times higher. By 2030, 20 percent of the U.S. population 
will be over age 65 compared with 12 percent in 2004. The cost 
consequences of this tsunami of baby boomers hitting their cancer-prone 
years could devastate our economy.
    A one percent decrease in cancer mortality is reported to be worth 
$500 billion to our economy according to an NCI report. Getting these 
potential new therapies I have outlined to patients will take a 
significant new investment in translational and clinical research, the 
cost of which can dwarf the cost of basic research. But without the 
most promising basic discoveries, we will not be able to improve early 
stage therapies and more and more translational and clinical endeavors 
will result in dead ends. We can't be shortsighted.
    We recognize the challenges each member of Congress faces in 
balancing worthy priorities, but I can assure you that from a 
scientific perspective there is justification for fully supporting 
basic, translational, and clinical pursuits. Basic science now more 
than ever fuels the success of effective disease diagnosis, treatment, 
and prevention in the future.
    Through the foresight of the members of this committee and others, 
the public has generously provided a start toward eradicating one of 
the scourges of human health. We are in fact in a better place to 
detect, treat, and potentially, prevent cancer. But just as new 
therapies based on our cellular and molecular understanding are 
emerging from our labs, the opportunity to expand them to other types 
of cancer, to build on them, and to provide for a future of more 
discoveries has idled. We can't retreat now that the infrastructure is 
in place and we are mobilized to launch a full force attack on a 
disease that we now understand. For the sake of the American people, 
please find a political route to keep progress against cancer at a 
sustainable pace. The research findings are clear. There is a path to 
major advances in cancer detection, diagnosis, therapy, and prevention. 
Help us get those advances to the public and fulfill the promises of 
the best in scientific research.
    Thank you for your time,

    Senator Harkin. Thank you, Dr. Brugge.
    I now will turn to Dr. Robert Siliciano, professor of 
medicine and molecular biology and genetics at the Johns 
Hopkins University School of Medicine. He received his A.B. 
degree in chemistry from Princeton, his M.D. and Ph.D. from the 
Johns Hopkins University School of Medicine.
    Dr. Siliciano, welcome, and please proceed.

STATEMENT OF ROBERT SILICIANO, M.D., Ph.D., PROFESSOR 
            OF MEDICINE AND PRINCIPAL INVESTIGATOR, 
            HOWARD HUGHES MEDICAL INSTITUTE, JOHNS 
            HOPKINS UNIVERSITY SCHOOL OF MEDICINE, 
            BALTIMORE, MARYLAND
    Dr. Siliciano. Mr. Chairman, thank you for inviting me to 
testify at this important hearing.
    Let me begin by commending you and Senator Specter for your 
foresight and efforts to double the NIH budget between 1998 and 
2003. As Dr. Zerhouni pointed out, we are on the cusp of a 
dramatic transformation in healthcare, which is the direct 
result of the Nation's investment in health science. I'm 
pleased to share with you my own experiences about this 
transformation and the vital role of funding basic research.
    When AIDS first appeared, in 1981, we had no idea what we 
were dealing with. Between 1981 and the present time, 
scientists have identified the virus responsible, deciphered 
its generic code, elucidated its lifestyle, developed a blood 
test, licensed 22 antiviral drugs, and learned a great deal 
about human immunology. A uniformly fatal disease has been 
transformed into one that can now be managed effectively with 
antiretroviral drugs. A recent study suggests that at least 3 
million years of life have been saved in the United States 
alone as a result of these treatments.
    These remarkable advances have come directly from basic 
science research. Many of the big advances came in the last 
decade. Many were funded by the NIH. The doubling in funding 
was central to much of that work. Yet we do not have a vaccine 
or a cure, and we're now struggling to cope with an epidemic of 
drug-resistant HIV.
    My laboratory, and Tony Fauci's lab at the NIH, have 
discovered how HIV hides in the body and escapes from the drugs 
that are being used to combat the infection. We've found that 
HIV can persist indefinitely in a latent state in long-lived 
cells of the immune system. In these cells, the HIV genome, is 
embedded into the host-cell DNA. As a result, the infection can 
never be cured by antiretroviral therapy alone. This discovery 
has changed the overall treatment paradigm from a hit-early-
hit-hard approach aimed at eradication to a more conservative 
approach aimed at maintaining lifelong control of viral 
replication.
    In addition to serving as a barrier to cure, this latent 
reservoir, as we call it, can also store drug-resistant HIV, so 
that if a patient develops resistance, they will always have 
that resistance.
    Right now, drug resistance is the dominant problem in 
treating HIV. At our clinic in Baltimore, half of the 3,000 
patients have multidrug-resistant HIV, and 10 percent of the 
new infections are with drug-resistant HIV. In developing 
countries, the problem of resistance is likely to become even 
more serious.
    Now, many laboratories would like to pursue studies on how 
to eliminate this latent reservoir and how to control drug-
resistant HIV, but, due to flat NIH budgets, research efforts 
are being scaled back. In my own lab, we're having difficulty 
taking on new student, and beginning new projects. In the past, 
I spent about 30 percent of my time applying for grants. Now 
it's up to 60 percent. Prominent investigators that I know in 
the field are getting out of research altogether. Fewer 
scientists want to tackle high-risk problems like this, because 
they know this kind of research will be difficult to fund.
    A colleague of mine has made a major discovery on a unique 
group of patients who control HIV without medication, has been 
unable to get funding.
    Although we have drugs that can control viral replication, 
we don't even know when therapies should be initiated. The 
definitive study of when therapy should be started may not be 
funded. Why? Because of insufficient funds for vaccine and 
treatment trials due to competition for diminishing NIH 
dollars.
    This is particularly unfortunate, because the return on NIH 
investment can be fantastic. For example, the discoveries made 
by AIDS researchers extend well beyond HIV. The discovery of 
how to evaluate levels of virus in the blood has revolutionized 
the treatment of patients with hepatitis B and hepatitis C 
infection, and will eventually be applied to all viral 
infections, including influenza.
    At Johns Hopkins, we've seen a marked decline in the level 
of research grants awarded. Fewer projects are being funded, 
and NIH support for ongoing projects is being cut. In 2002, the 
average funding per grant was approximately $142,000 for the 
School of Medicine; by 2006, it had dropped to $92,000, a 
decline of 34.8 percent.
    America's young researchers are being hit the hardest. I 
fear that we may lose a generation of inquisitive, enthusiastic 
scientists if they conclude that NIH funding is out of reach. 
According to the NIH, 8 out of 10 grant applications are turned 
down. This is a recipe for disaster.
    The situation extends well beyond healthcare. Federal 
investment in biomedical research is also critical to U.S. 
competitiveness.
    The United States has long been regarded as the world 
leader in scientific discovery, thanks, in large measure, to 
policies that encourage innovation. But today we face serious 
threats to this preeminence, as Dr. Zerhouni has mentioned. 
Other nations bring strong educational systems, focused 
government policy, and low-cost workers. Asia and Europe are 
committing unprecedented resources to scientific--to science 
and engineering.

                           PREPARED STATEMENT

    Basic science research is essential to America's ability to 
meet this challenge. In the United States, funding for basic 
research has long been a Government function. Why? Because 
basic research much be sustained for years, and even decades, 
sometimes with no discernible immediate return on the 
investment. No other entity, other than Government, can take on 
this role. Aggressive, stable, and sustained Federal spending 
on NIH and on biomedical research much be understood and 
embraced as a critical component to America's competitiveness.
    Thank you.
    [The statement follows:]

               Prepared Statement of Dr. Robert Siliciano

                              INTRODUCTION

    Mr. Chairman and members of the Committee, thank you very much for 
inviting me to testify today at this important hearing. I am Robert 
Siliciano, and I am a member of the Department of Molecular Biology and 
Genetics at the Johns Hopkins University School of Medicine.
    Let me start by commending you, Mr. Chairman and Senator Specter, 
for your efforts and foresight in doubling the National Institutes of 
Health (NIH) research budget between 1998 and 2003. Many of the amazing 
advances in health care treatment today are the result of federal 
investment in research identifying early indicators and causes of 
diseases. I am convinced we are on the cusp of a dramatic 
transformation in health care, which is a direct result of the nation's 
investments in health science discovery and cures. My fellow 
researchers on the panel and I are pleased to be here today to tell you 
about this transformation.
    On behalf of myself and all my colleagues at Johns Hopkins, I would 
like to recognize the persistence of many on this committee for your 
ceaseless support of NIH's work. I would also take this opportunity to 
invite you to visit our campus in Baltimore to see for yourselves the 
exciting work that my colleagues and I--not to mention our students--
engage in every day. You will find no more persuasive argument for the 
value of investing in research than witnessing innovation firsthand.

                  NIH SUPPORT FOR MY WORK ON HIV/AIDS

    Early in the AIDS epidemic, an AIDS patient could expect to enter 
hospice care within a few years after the diagnosis. However, 
significant research developments in the area of ``Highly Active Anti-
Retroviral Therapy,'' or HAART--that combination of drugs commonly 
referred to as the ``AIDS cocktail'' has lead to increasing the 
survival rate of those diagnosed with HIV. This therapy involves a 
variety of drugs that attack the virus at different stages of its life 
cycle, thus reducing its ability to replicate itself in healthy cells. 
HAART combines drugs that were developed during some of the first 
stages of AIDS research. By 1990, monotherapy--treatment using one 
nucleoside analog--was showing some promise, but debate persisted in 
the research community as to which of this class of drugs were the most 
useful. In 1995, studies showed that treatment with simultaneous use of 
two nucleoside analogs would prove more effective in prolonging life. 
By 1997, combination therapy had expanded to include protease 
inhibitors and non-nucleoside reverse transcriptase inhibitors, both 
classes of drugs that attack HIV as it attempts to insinuate itself 
into healthy cells.
    The result of HAART has been the transformation of AIDS from a 
disease that meant rapid and certain death to a chronic condition that 
can now be managed over a patient's lifetime. When widespread use of 
HAART began in the mid 1990s, U.S. mortality rates immediately 
plummeted--from nearly 41,000 in 1995 to 17,000 in 1997. HAART even 
proved effective for patients who had already reached the terminal 
stages of the disease; many were able to leave hospice care and return 
to relatively normal lives.
    For the more than 40 million people infected with HIV, the best 
current hope for avoiding the fatal consequences of the infection lies 
in treatment with HAART. The benefits of HAART in reducing mortality 
are clear, but major questions remain about how best to use HAART and 
how to make it available to all who need it.
    Our work has shown that current HAART regimens cannot cure the 
infection in most patients because the virus persists in a very stable 
latent reservoir in resting memory CD4+ T cells (cells that control the 
activities of all of the other cells). Because HAART is not curative, 
treatment of HIV infection is a lifelong challenge. Most infected 
individuals will ultimately have to depend upon HAART to avoid fatal 
immunodeficiency. Problems of drug resistance and drug toxicity make 
this an alarming prospect.
    My lab is interested in understanding viral persistence and in 
applying basic studies of viral dynamics in HIV infection to optimizing 
antiretroviral therapy. Our work on viral persistence began in 1994, 
with the idea that the capacity of HIV to establish a state of silent 
or latent infection at the level of individual cells might provide a 
mechanism for viral persistence in the face of immune responses and 
antiretroviral therapy. We hypothesized that HIV might capitalize on an 
extremely fundamental aspect of the immune system, immunologic memory, 
to ensure its persistence in the host.
    At any given time, most of the lymphocytes in the body are in a 
resting state. When a lymphocyte encounters a bacterial or viral 
protein that it is programmed to recognize, it becomes activated and 
begins to proliferate, generating effector cells that eliminate the 
invading microorganism. Most of these effector cells die, but some 
survive and return to a resting state as memory cells. These cells 
persist indefinitely, allowing effective responses to future challenges 
with the relevant microorganism.
    HIV preferentially infects activated CD4+ T lymphocytes, inserting 
its genetic information into the genome of the host cells and directing 
the production of new virus particles in a process that usually leads 
to the death of the infected cells. However, a small subset of the 
activated CD4+ T cells that are infected with HIV survive long enough 
to revert back to a resting memory state. Because the expression of HIV 
genes depends on host transcription factors induced in activated T 
cells, viral gene expression is automatically extinguished when these 
cells return to a quiescent state. The result is a stably integrated 
but transcriptionally silent form of the HIV genome in a memory T cell, 
a cell whose function it is to survive for years in a quiescent state. 
Upon subsequent re-exposure to the relevant microorganism, the latently 
infected cell is reactivated and becomes competent for HIV gene 
expression and virus production. Over the past several years, we have 
been able to demonstrate the presence and persistence of latently 
infected resting memory CD4+ T cells with integrated HIV DNA in 
infected individuals. The cells are present only at low frequencies, 
reflecting the fact that most productively infected CD4+ T cells die 
before they can revert back to a resting memory state. Particularly 
important is whether this small reservoir of latent virus persists in 
patients on HAART. In the years following the advent of HAART, which 
began in the mid-1990s, there was considerable optimism that virus 
eradication might be possible with prolonged treatment, based on 
analysis of the rapid decay of plasma virus to undetectable levels 
following the initiation of HAART.
    We have shown, however, that the frequency of latently infected 
cells does not decrease even in patients on HAART who have had 
suppression of viremia to undetectable levels for as long as seven 
years. As a result of this discovery in 1999, the overall approach to 
the treatment of HIV infection has significantly changed. In 
particular, it became more conservative. Patients were no longer 
started on therapy as soon as they were diagnosed. Initiation of 
therapy was delayed until later stages of disease, since there was no 
hope of eradication. This work raised the possibility that the virus 
could persist indefinitely in all patients on HAART, leading many 
investigators to question the wisdom of beginning aggressive therapy 
with the goal of eradicating the infection, particularly in light of 
the substantial long-term toxicities of HAART regimens.
    Several additional findings add to the seriousness of the problem 
presented by the latent reservoir. We have shown that this reservoir is 
a permanent archive for drug-resistant viruses that are generated by 
inadequate treatment. Once drug-resistant viruses have entered the 
reservoir, they persist there indefinitely, permanently restricting the 
patient's therapeutic options. The problem of stored drug-resistance 
mutations is particularly severe in the case of perinatally infected 
children, who face a lifetime of treatment.
    In 2000, we demonstrated the presence and persistence of this 
latent reservoir in these children. In addition, we have demonstrated 
that latency operates at the transcriptional level. Latently infected 
cells carry integrated HIV DNA but contain little translatable HIV RNA. 
Unfortunately, the last hope for detecting and targeting latently 
infected cells was that the cells might be expressing low levels of 
particular viral proteins, allowing recognition by immune effector 
mechanisms. It now appears that we may be dealing with a completely 
silent form of latent infection that will be difficult to target with 
antiretroviral drugs or HIV-specific immune responses. These findings 
apply not only to children but to all HIV patients.
    In 2001, we became interested in understanding the nature of the 
low-level virus production that continues in patients on HAART whose 
plasma virus levels are below the limit of detection of standard 
assays. We have developed methods for cloning and characterizing the 
extremely low levels of plasma virus that are present in such patients. 
We have shown that this virus is generally archival in nature, is 
devoid of new drug-resistance mutations, and may be derived from the 
activation of latently infected cells. Most importantly, we do not see 
evidence for the continued evolution of drug resistance in most 
patients on suppressive HAART regimens. This provides a counterpoint to 
our disheartening findings on the stability of the latent reservoir. 
Although current HAART regimens cannot produce eradication because of 
the extraordinary stability of the latent reservoir, they can largely 
halt virus evolution, affording patients the possibility of lifelong 
suppression of viremia if the problem of drug toxicity can be overcome.
    It is important to point out that despite the spectacular advances 
that have been made in anti-retroviral therapy--at least 3 million 
years of life have been saved in United States alone--the definitive 
study that would allow us to determine when exactly treatments should 
commence may not be funded because of insufficient funds for vaccine 
and treatment trials. An unfortunate tension exists due to this 
competition for diminishing NIH dollars.
    It is also worth pointing out that the discoveries our community of 
researchers have made extend well beyond HIV. What we have learned from 
studies of HIV can be applied to other viruses. For example, we have 
learned how to measure the amount of virus in the blood. This 
knowledge, which has provided us with a real-time measure of the amount 
of viral replication in a patient, along with the importance of 
utilizing it to treat viruses such as influenza and Hepatitis B and C, 
has revolutionized the success of these treatments.
    In the future, we hope to address several critical questions 
related to the molecular mechanism of HIV latency and the clinical 
implications of this form of viral persistence. We are interested in 
whether it will ever be possible to eliminate this reservoir. 
Furthermore, we hope to translate our findings on mechanisms of viral 
persistence into new approaches for optimizing antiretroviral therapy. 
The correct choice of a HAART regimen is literally a matter of life and 
death for many patients, and we feel basic studies of viral persistence 
can be applied to improving decisions about how and when antiretroviral 
therapy should be given. Over the years, this research has received 
nearly $7 million in support from the NIH.
    I want to emphasize that many labs would like to pursue the problem 
of how to eliminate the latent reservoir, but everyone I know has had 
to scale back research efforts because of flat NIH budgets. In my own 
lab we are now finding it difficult to take on new staff and begin new 
projects. Typically, in the past, I would spend about 30 percent of my 
time applying for grants; now about 60 percent of my time is spent 
preparing applications. Furthermore, some prominent investigators are 
getting out of research. Few scientists want to tackle high-risk 
problems like this because research of this type is more difficult to 
fund. In fact, a very good colleague of mine has made a major discovery 
on a unique group of patients who control HIV without medication. He 
has not been able to get funding even though the potential savings is 
more than $14,000 annually per patient. Additionally, a mentor of mine, 
and one of the most respected people in the field, is thinking of 
getting out of research because he has no funding.
federal investment in research is a critical component of our nation's 

                            COMPETITIVENESS

    The United States has long been the world leader in scientific 
discovery, thanks largely to government policies that encourage 
innovation, improve education, and facilitate the transfer of knowledge 
from the laboratory to the marketplace. Today we face serious threats 
to this preeminence. Other nations bring to the table strong 
educational systems, focused government policies, and low-cost workers.
    Basic research is essential to our ability to meet this challenge. 
William R. Brody, president of The Johns Hopkins University and co-
chair of a national committee on competitiveness, puts it this way: 
``Knowledge drives innovation. Innovation drives productivity. 
Productivity drives economic growth.'' Our ability to compete in the 
global economy depends, first and foremost, on our ability to continue 
making new discoveries. The more we learn about how things work--the 
principles of basic biology, chemistry, physics, and mathematics--the 
more opportunity we have to put that knowledge to work. When we know 
more, we can use that knowledge to make our world better, to build new 
businesses, devise new products, and to improve our standard of living.
    America's most innovative industries are built on decades of basic 
research, research that had no discernable practical application at the 
time it was undertaken. For example, the highly theoretical world of 
quantum mechanics spawned the semiconductor industry and the 
information revolution. Johns Hopkins scientists thinking about the 
principle of physics, called the Doppler effect, used it to invent what 
became today's Global Positioning System. Two Johns Hopkins biologists 
shared a Nobel Prize in 1978 for using restriction enzymes to cut DNA 
into fragments that created today's thriving biotechnology industry, 
which is based on genetics.
    In the United States, funding basic research has long been a 
governmental function. Why? Because it takes a long time to do it, 
because there is always a risk that any single project will come to 
nothing, and because it is difficult to capture an immediate return on 
investment for an idea that has not yet been developed to the stage of 
a marketable invention.
    Despite a societal consensus that basic research is a government 
responsibility, U.S. Federal research and development spending, as a 
percentage of Gross Domestic Product (GDP), peaked 40 years ago in 
1965, at just below 2 percent of GDP. In the past 40 years, that 
percentage has diminished by more than half, to about 0.8 percent of 
GDP. Overall R&D spending, especially in basic sciences, continues to 
decline. We must reverse this trend now, by strengthening the Nation's 
commitment to science related federal agencies and departments.
    The investments in biomedical research being made by rising 
economic powers such as China are increasing. While China lacks a 
central institution like the NIH to oversee its national investment in 
biomedical research, its National Science and Technology Plan for 2006-
2020 emphasizes a long-range strategy to raise its biomedical research 
to world-class standards. This is being supported by a pledge to raise 
R&D spending from 1.3 percent of GDP in 2005 to 2.5 percent by 2020 
(Science 9 March, 2007: Vol. 315. no. 5817).
    If we look to one promising field of the future--that of nanotech--
overall government spending globally grew by 10 percent to $6.4 billion 
in 2006. According to a report released by Lux Research, the United 
States came out on top, with $1.78 billion, followed by Japan and 
Germany. But China actually ranks second when purchasing power parity 
is considered. China's funding is the equivalent of $906 million. (UPI 
9 March, 2007). In this sector, like so many others, China will 
compete.
    The life sciences research funded by the NIH is a key component of 
our overall national science agenda. For example, Johns Hopkins 
University is the nation's leading recipient of federal research 
grants. In fiscal year 2005, our researchers attracted nearly $1.3 
billion in federal R&D funding and $1.4 billion in overall R&D funding, 
a category in which Johns Hopkins has led all U.S. institutions for 27 
consecutive years. This support enables us to improve medical care 
worldwide, advance human knowledge, and train new generations of 
innovative researchers.
    Investment in research universities like Johns Hopkins yields 
tangible economic benefits as well. In 2006, Johns Hopkins researchers 
filed more than 420 U.S. patent applications, received 79 U.S. patents, 
and licensed 72 technologies for commercial development. Some of these 
inventions will be commercialized by Maryland companies. Already, there 
are at least 19 existing Maryland-based start-ups bringing Johns 
Hopkins technology to market. That is a tremendous amount of knowledge 
made available to American business and the American public for an 
incalculable range of benefits.
    While the President and Congress have embraced the notion that 
funding for basic research in the physical sciences is essential to 
strengthening America's competitive standing in the world, and Johns 
Hopkins certainly recognizes and appreciates the significant 
investments included in the fiscal year 2007 Continuing Resolution, we 
remain concerned that funding for biomedical research has not kept pace 
with this commitment. Aggressive, stable, and sustained federal 
spending on the NIH and biomedical research must be understood and 
embraced as a critical component of America's competitiveness.

                      JUSTIFICATION OF NIH FUNDING

    On January 15, 2007, President Bush signed the National Institutes 
of Health Reform Act of 2006. While the law calls for a 6 percent 
increase for fiscal year 2007 and an 8 percent increase for fiscal year 
2008, the reality is that this funding commitment has not fully 
materialized. For fiscal year 2006, the NIH budget was cut in both 
nominal and real terms. For fiscal year 2007, the NIH received a modest 
yet important increase of approximately $620 million. We are very 
grateful that this Congress chose to single out the NIH, along with 
several other science agencies, to be among the few areas of federal 
spending to receive increases. We recognize that budgets are tight and 
we see this as a critical statement of Congress' desire to strengthen 
and preserve the scientific enterprise in this country. Despite this 
increase, however, fiscal year 2007 marks the fourth year in a row, 
when adjusting for inflation, that NIH funding has been cut.
    At Johns Hopkins, we have annually led the nation in NIH research 
dollars and we have seen a marked decline in grants awarded to our 
School of Medicine. Fewer projects are being funded and NIH support of 
on-going investigations is being cut. Recent figures suggest that the 
number of grants and overall funding levels have declined. In fiscal 
year 2002, the average funding level per grant was $142,210 for the 
School of Medicine. By fiscal year 2006, the funding level dropped 
nearly $50,000 per grant to $92,683, a decline of 34.8 percent. Hardest 
hit are America's young researchers. I fear that we may lose a 
generation of enthusiastic, inquisitive scientists if they conclude 
that NIH grants are out of reach.

             FLAT FUNDING THREATENS OUR YOUNG INVESTIGATORS

    One of the first and earliest victims of declining NIH funding has 
been the young investigator. You have heard today, and often over the 
past several years, from Dr. Zerhouni regarding NIH's concern that we 
are potentially sacrificing an entire generation of young scientists. 
The Director's concern is real and very serious.
    Quite simply, we have to do more to support and encourage our young 
investigators. Most ideas that turn into Noble Prizes come from 
investigators before they reach the age of 40. As a country, then, 
shouldn't we be supporting these scientists when they are in their 
professional prime? Unfortunately, the statistics tell an entirely 
different story. In the case of initial R01/R29 awards, between 1970 
and 2004, the average age by which an investigator with a Ph.D gains 
his or her first award has gone from 34.3 years of age to 41.7. In the 
case of MDs, during this same period, that age has gone from 36.7 years 
to 43.3 (AAMC 12 July, 2006). With diminished NIH funding, our young 
scientists are witnessing firsthand the decline in overall success 
rates for grant applications. In 1998, the first year of the doubling, 
overall success rates were about 31 percent for grant submissions. For 
2007, the success rate is projected to drop to only about 19 percent. 
Left unaddressed, there is no question that the current decline in NIH 
funding places an entire generation of young scientists at risk.
    Even at my own institution, where we have many of the best and 
brightest among the current generation of young scientists, we are 
seeing many of these men and women unable to gain funding support. 
Without sustainable and predictable increases in NIH funding, this 
nation is at risk of losing an entire generation of scientists.

                   RESEARCH IMPACTS HEALTH CARE COSTS

    When advocates for increasing biomedical research funding meet with 
members of Congress and their staff, they are often asked: ``What have 
we to show for the money that NIH has received in the past?'' As we 
think about this question, it is important to recognize that the pace 
of biomedical research and science in general is often slow and 
unpredictable. It may be years before we can point to specific 
therapies or new medical devices that can trace their origins to 
recently funded efforts. But the simple answer is: We have a great deal 
to show!
    Here are three powerful examples--there are, of course, many more--
of what Johns Hopkins scientists have accomplished in terms of 
improving healthcare and reducing costs, thanks to NIH support.
Detection of Vision Problems of Diabetics
    Diabetes is the leading cause of blindness in adults, with 12,000 
to 24,000 new cases each year. Early identification of retina disease 
is critical to stave off vision loss, especially for the 10 million 
diabetics who are 60 years or older, most of them on Medicare or 
Medicaid. Yet more than half of all diabetics fail to get an annual eye 
exam as recommended by the American Diabetes Association. To address 
this dilemma, Dr. Ran Zeimer, director of the Ophthalmic Physics 
Laboratory at the Johns Hopkins Wilmer Eye Institute, came up with a 
novel solution after more than a decade of research: Why not develop an 
easy-to-use digital camera that tests for retinopathy when diabetics 
visit their primary care physicians for check-ups?
    Thanks to NIH support, Dr. Zeimer perfected an instrument called 
the DigiScope. The DigiScope takes images of the retina in just minutes 
as patients sit in front of an automated camera and look at a series of 
blinking lights. These images are then transmitted via the Internet to 
a reading center for expert interpretation. More than 20,000 
individuals not under the care of an ophthalmologist have been screened 
to date in the offices of primary care physicians. Those with vision-
threatening disease have been identified and referred to eye 
specialists. In most cases, diabetics without complications are spared 
visits to an ophthalmologist, while Medicare and Medicaid are spared an 
expense.
Advances in Treatment for Sickle Cell Patients.
    Thanks to continuous NIH grants extending back to 1982, Drs. George 
Dover and Samuel Charache of Johns Hopkins spent their careers fighting 
sickle cell disease--a miserable, inherited illness in which sickle-
shaped red blood cells get stuck in narrow channels and block blood 
flow to tissue and vital organs. Patients with sickle cell disease--
72,000 in the United States--suffer frequent bouts of fatigue and 
shortness of breath, joint and body organ pains that turn excruciating 
and lead to frequent hospitalizations. The pneumonia-like conditions, 
chest pains, and fever can be life-threatening. Until fairly recently, 
early death was the norm, with life expectancy for a sickle cell 
patient projected to be only 20 to 30 years.
    In the 1990s, Drs. Dover, Charache, and their Hopkins research team 
found that a cancer drug (hydroxyurea) did remarkable things for sickle 
cell sufferers. A 1995 NIH-supported multi-center study proved that 
hydroxyurea therapy dramatically reduces the frequency and severity of 
painful episodes, hospitalizations and transfusions. In a 2003 study, 
daily doses led to 30 percent fewer hospital days, 58 percent fewer 
transfusions, and a 40 percent reduction in deaths. Today, hydroxyurea 
therapy is recommended for adults and adolescents with moderate-to-
severe recurrent pain. As a result, the life expectancy for sickle cell 
patients has doubled.
    There have been financial benefits, too. According to another NIH-
sponsored study, hydroxyurea therapy saves the U.S. health care system 
$5,210 per sickle cell patient per year. With 72,000 Americans 
suffering from sickle cell disease, the potential annual savings is 
more than $375 million annually.
Faster Diagnoses in Emergency Rooms
    With the existing threat of bioterrorism, it is crucial to find 
ways to swiftly identify patients in hospital emergency rooms who have 
biochemical pathogens or life-threatening infectious diseases, such as 
meningitis, sepsis, and bacterial endocarditis (an infection of the 
inner lining of the heart or heart valves). Current testing methods are 
time-consuming and usually lead to delays in diagnosing and treating 
these diseases. The current blood and culture tests for some diseases 
can take 24 hours or more.
    Dr. Richard E. Rothman of the Johns Hopkins Department of Emergency 
Medicine is working on novel ways to identify quickly multiple blood-
borne and pulmonary infectious diseases and bioterrorism pathogens. His 
patented molecular diagnostic tests involve both exhaled breath and 
body fluids. Early experiments have shown that these new diagnostic 
tools can detect 25 common bacterial infections and five categories of 
bioterrorism agents in fewer than 4 hours. Faster response times are 
expected as the diagnostic tools are fine-tuned.

                               CONCLUSION

    Thank you for your efforts to strengthen America's biomedical 
research community. Johns Hopkins stands ready to support you in this 
important endeavor. I invite you and your staff to visit our campuses, 
explore our facilities, and meet our researchers who are taking the 
lead in these vital fields.

    Senator Harkin. Dr. Siliciano, thank you very much. I'll 
have some questions about the drop in GDP, also.
    Now we'll turn to Dr. Stephen Strittmatter, professor of 
neurology and neurobiology at Yale University School of 
Medicine. Dr. Strittmatter earned his undergraduate degree from 
Harvard and his M.D. and Ph.D. degrees at Johns Hopkins.
    Dr. Strittmatter?

STATEMENT OF STEPHEN M. STRITTMATTER, M.D., Ph.D., 
            PROFESSOR OF NEUROLOGY AND NEUROBIOLOGY, 
            YALE UNIVERSITY SCHOOL OF MEDICINE, NEW 
            HAVEN, CONNECTICUT
    Dr. Strittmatter. Chairman Harkin, I thank you for the 
opportunity to share some of my thoughts on NIH-supported 
science and the NIH budget.
    To be frank, my three decades in clinical neurology and 
basic neuroscience have convinced me that the recently flat NIH 
budget is stifling creative high-risk research. On the one 
hand, the doubling of the NIH budget that was provided by 
Congress and championed by you and the rest of this 
subcommittee has laid the foundation for fantastic advances, 
revolutionizing the care of patients with nervous-system 
diseases; however, for most types of neurologic and psychiatric 
diseases, we still face a crucial hurdle: the translation of 
basic molecular analysis of brain function into effective 
treatments. To leap over this translational hurdle requires the 
most creative and risk-taking experiments, including those that 
may lead to an experimental dead-end before achieving a 
critical insight towards a new therapy.
    Regrettably, the decline of inflation-adjusted NIH spending 
in recent years has produced a marked chilling effect 
specifically on this type of research. If that's not reversed, 
we're going to fail to reap the full benefits of the expansion 
that occurred from 1998 to 2003 in research in the United 
States.
    My own field in neuroscience relates to nerve-fiber growth 
and provides one example of how high-risk research can succeed 
when the environment is appropriate. In humans, single nerve 
cells extend fine threads, called axons, for very long 
distances, up to 3 feet. You can imagine, if the cell body were 
blown up to the size of a baseball, the axon would be the width 
of a pencil and extend for half a mile. When all these nerve 
fibers are correctly connected, this provides the wiring of the 
brain, and the function of the brain is critically dependent on 
all this being connected correctly.
    During the 1990s, molecular insights into the basis of axon 
guidance advanced very rapidly. We identified dozens of axon 
guidance molecules and genes that help put the brain together. 
These molecular insights were fascinating, but they didn't 
immediately improve human health. So, the next step was to 
apply this knowledge to settings of neurologic injury, where 
axonal disconnection occurs. The clearest example of this, 
one--a field that I work in--is traumatic spinal cord injury. 
Despite the profound, and the persistent, neurologic deficits 
that occur after spinal cord injury, such as the inability to 
move or feel below the level of the injury, nearly all of the 
nerve cells remain intact. The primary cause of disability is 
the disconnection of one nerve cell from another, not the loss 
of cells. Very little axon regrowth occurs after injury, and 
this is why there's very little recovery in adults.
    So, here's the translational problem, the hurdle, to 
overcome. How do we use basic knowledge about axon growth to 
restart--during development--how do we use that to restart 
adult axon growth, repair function, and recover ability of 
people to live a productive life? It's certainly a problem that 
I wanted to take on as a neurologist caring for patients while 
running a basic developmental laboratory. However, without the 
sort of environment that was created by the budget doubling 
through the NIH funding, I wouldn't have tackled this problem 
myself. But when I did take it up, in that time period, we 
discovered, in my laboratory, a molecule, termed Nogo, that 
prevents nerve fiber growth. By analyzing the mechanism of 
action of this Nogo molecule, we identified genetic, and then 
pharmacologic means to prevent its function; thereby, 
stimulating nerve fiber growth. Remarkably, therapy with a Nogo 
receptor antagonist allows rats to walk after spinal cord 
injury or to recover better paw use after a stroke. Today, a 
closely related approach using an antibody against Nogo is in 
clinical trials.
    So, I think this illustrates how high-risk research can 
occur. But I'm convinced that similar challenges in Alzheimer's 
or in schizophrenia research are not being tackled today, 
because of the limitations that have occurred in the NIH 
budget. The reason I say that is that when researchers and 
peer-review panels are faced with the idea that junior 
investigators can't be funded at all, or that senior 
investigators are losing funding, everyone shifts towards what 
I'd call ``safe science.'' Scientists pursue those experiments 
that have the highest probability of success in the short term, 
incremental gains. They shy away from the paradigm-shifting 
discoveries that will really move science into the clinic, 
where it will solve the major health problems that we have 
caring for this country.
    Researchers essentially become worriers focused on how to 
maintain their laboratories, rather than explorers seeking to 
solve the crucial issues. High-risk, high-payoff studies are 
what we need most, but they have the most volatile dependence 
on the NIH funding level.

                           PREPARED STATEMENT

    Of course, Dr. Zerhouni and the NIH have recognized the 
need for this kind of research, and they've taken steps to 
achieve it within the confines of the NIH budget. This is 
certainly important and commendable, but it's not a substitute 
for the kind of investment of Federal funds that will encourage 
creativity and reward risk. Specialized programs or set-asides, 
by definition, can only affect a small percentage of all the 
research that's going on. Moreover, creativity cannot be 
dictated by policy alone. Only a reversal of the inflation-
adjusted decline in the NIH budget can reset the community's 
outlook. By establishing an NIH funding level that, at a 
minimum, restores recent net losses to inflation and keeps pace 
with costs in the future, Congress, this committee, can achieve 
the research environment required to promote the health of all 
of our citizens.
    Thank you very much.
    [The statement follows:]

           Prepared Statement of Dr. Stephen M. Strittmatter

    Chairman Harkin, and Members of the committee, I thank you for the 
opportunity to offer my insights on the NIH budget. To be frank, my 
three decades in clinical Neurology and basic Neuroscience research at 
Yale, Harvard and Johns Hopkins have convinced me that the recently 
flat NIH budget is stifling creative, high-risk research endeavors.
    The doubling of the NIH budget provided by Congress, and championed 
by many of you on this committee, laid the foundation to revolutionize 
the care of those suffering with nervous system diseases. However, for 
most types of neurological and psychiatric disease, we still face the 
crucial hurdle: the translation of basic molecular analysis of brain 
function and dysfunction into effective treatments. To leap over this 
translational hurdle requires the most creative and the riskiest 
experiments, including those that may lead to an experimental dead-end 
or multiple failures before achieving the one critical insight that 
will establish a new therapy. Regrettably, the decrease of inflation-
adjusted NIH spending in recent years has produced a marked chilling 
effect on precisely the type of research that is most needed. If this 
chilling effect is not alleviated, we will fail to reap the full 
benefits of the research expansion that occurred from 1998-2003--and we 
will push better treatments farther into the future.
    My own field in Neuroscience relates to nerve fiber growth, and 
provides an example of how high-risk research can succeed in the 
appropriate environment. In humans, single nerve cells extend fine 
threads, called axons, for distances as long as a meter. If the cell 
were magnified to the size of a baseball, the axon would be the width 
of a pencil and extend for half of a mile. These axons conduct 
electricity and provide the ``wiring'' of the brain. There can be no 
useful brain function unless these fibers are correctly connected, and 
failure to connect--or reconnect--contributes to many diseases, from 
strokes, Alzheimer's and Parkinson's to Multiple Sclerosis and Lou 
Gehrig's disease.
    Twenty years ago when I started in this field, little, if anything, 
was clear about how the cells of the developing brain become connected 
over long distances. However, molecular insights into the basis of 
axonal guidance began in the early 1990's and the pace of discovery 
accelerated rapidly during the NIH budget doubling. Basic studies led 
to the identification of dozens of axon guidance molecules and genes 
with defined roles in the developing brain.
    These molecular insights were fascinating from the scientific 
perspective, but did not immediately improve human health. The next 
step was to apply this knowledge to settings of brain injury where 
axonal disconnection occurs. The clearest example is traumatic spinal 
cord injury. Despite the profound and persistent neurological deficits 
after spinal cord injury, such as the inability to move or feel, nearly 
all of the neurons that initiate arm and leg movements and provide skin 
sensation survive injury. The primary cause of disability is the 
interruption of nerve fibers--not the loss of cells. This, we learned, 
has important implications for treatment.
    Inside the brain and spinal cord, very little axon regrowth occurs 
after injury, explaining the poor recovery of adults. Here the 
translational hurdle emerged: how do we use basic knowledge of 
embryonic fiber growth to restart axonal growth and restore proper 
function after injury or disease. As a Neurologist caring for patients 
while directing a brain development laboratory, I was particularly keen 
to attack this hurdle. Despite my interest, I would not have pursued 
this goal in 2000 without the risk-taking climate created by the NIH 
budget doubling.
    We discovered the existence of a molecule, termed Nogo, which 
prevents nerve fiber growth, and mice lacking the gene for Nogo or its 
partner NogoReceptor exhibited significant axonal regeneration. 
Moreover, such animals recover substantial walking after spinal cord 
injury, or improved paw use after stroke. By analyzing the action of 
the Nogo molecule, we identified methods to prevent its function. 
Remarkably, therapy with a NogoReceptor antagonist allowed rats to walk 
after spinal cord injury and those with strokes recovered greater paw 
use. Today, a closely related approach using an antibody directed 
against Nogo is in clinical trials.
    While this story illustrates past progress in high-risk research, I 
am convinced that similar challenges are not being tackled today 
because of the NIH budget situation. When researchers and peer review 
panels are faced with many junior investigators failing to achieve NIH 
research support and established investigators losing support, the 
first change is a retrenchment to ``safe'' science. Scientists pursue 
those experiments that have the highest probability of achieving an 
incremental short-term goal, rather than a chance of generating a 
paradigm-shifting long-term discovery. Researchers have become 
``worriers'' focused on how to maintain their laboratories and jobs, 
rather than ``explorers'' seeking to solve the most crucial 
translational issues. High-risk, high-payoff studies have the most 
volatile dependence on NIH funding levels. Nonetheless, we require 
high-risk endeavors now more than ever to take advantage of basic 
science and research tools developed during the doubling of the NIH 
budget.
    Dr. Zerhouni and the NIH have recognized the need for high-risk, 
high-payoff research and have taken steps to foster such work within 
the confines of restricted NIH budgets. This is important and 
commendable but it is not a substitute for an investment of federal 
funds that encourage creativity and reward risk. Specialized programs 
and set-asides can only affect a small percentage of biomedical 
research by their very nature. Furthermore, creativity cannot easily be 
dictated by policy. Only a reversal of the inflation-adjusted decline 
in the NIH budget can reset the biomedical community's outlook.
    Future health care can be dramatically improved if researchers 
explore the highest risk research areas, allowing researchers to clear 
the translational hurdle and bring the benefits of expanding basic 
science to the public. By setting an NIH funding level that, at a 
minimum, restores recent net loses to inflation and keeps pace with 
costs in the future, Congress can achieve the research environment 
required to improve health for all of our citizens. I would be pleased 
to answer any questions.

    Senator Harkin. Thank you very much, Dr. Strittmatter
    Just some general questions for the panel. We've all heard 
about the drop in the success rates, from 1 in 3 to about 1 in 
5 right now. Some institutes are rated even lower. I'm 
concerned that when you get that low, some scientists, 
especially the young investigators, will just say, ``Why 
bother?'' You've all kind of spoken to that, in one way or the 
other. But what's the minimum success rate that makes sense? 
What should we be aiming for? Is there something we should be 
aiming for? What's the minimum? I just open it up.
    Dr. Strittmatter. Well, I don't know if there's one 
minimum. There's not one answer to the question. I think Dr. 
Zerhouni put forth the notion that, historically, the success 
rate of grants had been around 30 percent. That's one where the 
culture of research in the United States is comfortable with 
the idea that we choose the best grants, we move forward with 
the best ideas. The problem now is that that funding rate has 
gone down, so we not only--the feeling that scientists have is 
not that creativity or risk-taking is rewarding, but that we 
should shut down. We're going backwards, not forward. So, 
perhaps reaching back to that historical level, not 100-percent 
funding, but----
    Senator Harkin. Yeah.
    Dr. Strittmatter [continuing]. 30-percent success rate in 
grants, will restore the kind of driving forward of the 
research, moving science into changing healthcare that we need.
    Senator Harkin. That's----
    Dr. Strittmatter. That's one answer. I don't know----
    Senator Harkin [continuing]. Sort of, overall. Should there 
be some areas where it should be higher than 30 percent?
    Dr. Strittmatter. Well, I think one way to judge that would 
be whether there's--what you'd really want to know is whether, 
on the margin, the grants that are funded discover something 
useful, advance healthcare. If funding levels were at 30 
percent, do the worst 1 percent or 2 percent of the grants help 
the American public? I think you could easily argue that the 
enormous cost of healthcare--they're so large that looking for 
cures, or preventive, pre-emptive medicine, has such a huge 
financial benefit--I think that's what Dr. Zerhouni alluded to 
with his figure of $44 per person in the United States for all 
of the NIH budget. You could easily argue that we should be at 
a higher level, and we would still save immense amounts of 
money compared to the amount that we spend on healthcare and 
insurance otherwise. That's one answer.
    Dr. Iverson. If I could answer that specifically--excuse 
me--I would say that, from my perspective, I think 30 percent 
is a great number. I would also like to see an allocation for a 
common fund that can be targeted at particularly exciting 
opportunities that should not fight each other.
    Senator Harkin. Uh-huh. Anything else?
    All right. The other thing--Dr. Siliciano, you pointed out 
in your statement--you didn't state it, but I read it--and it 
said that--when was it? In 1965, we peaked at the percent of 
our GDP that went for--was that all R&D--I guess, just all R&D 
lumped together? Now it's about eight-tenths of 1 percent.
    Dr. Siliciano. Yes, I believe so.
    Senator Harkin. Then you pointed out that China had just 
recently committed going from 1.3 percent, where they are now--
so, they're even higher than we are as a percent of GDP--to 2.5 
percent of GDP by 2020. I'm going to have my staff find out 
what it would be if we were at 2 percent right now? I just 
wonder what the figure might be. I didn't see it there, but we 
can find that out. I just didn't know if you knew it, off the 
top of your head.
    Dr. Siliciano. I don't--not off the top of my head.
    Senator Harkin. Well, obviously it would, what, at least 
2.5 times where we are right now.
    The other thing that I--you talked about these--about 30-
percent approval rates and what should the right number be, 
what should we aim for. I still don't know if I got a good 
handle on that. But I also wonder about the whole peer-review 
process--and I have brought this up for the last 20 years that 
I've been on this Committee--on the one hand, you want good 
peer reviews, because you want good, legitimate science being 
done. So, you want those that are knowledgeable in those areas 
to look at it and give their evaluation as whether or not it's 
legitimate, sound, and should go forward or not. It's a good 
system. On the other hand--on the other hand, peer reviewers 
tend to be those that have been in that area of scientific 
research for some length of time, they have all pursued certain 
interests. You know, maybe they're looking for the safer 
things, the things that they're comfortable with, that they 
have more understanding of. I'm often wondering, do these sort 
of off-the-wall kinds of things that--the new-paradigm types of 
research that some of you spoke about, do they--what's your 
comfort level that some of these actually get through that 
peer-review process, these kind of really new things that maybe 
a peer-reviewer had never, ever been involved in before--how do 
they get through that?
    Dr. Siliciano. Mr. Chairman, I've had quite a bit of 
experience on these type of review panels, and my overall 
impression is that they do a really excellent job of finding 
the good science. There has been a mandate on these panels, for 
many years, to look for what's called high-risk/high-yield 
types of projects. My own experience is that those types of 
projects do get funding. The biggest--and I think the overall 
system works extremely well. I'd be anxious to hear what my 
colleagues think. But I think the problem is that the amount of 
funding that the system has at its disposal right now is just 
too low to allow the system to work effectively. When you go 
down from 30 percent grants being funded to----
    Senator Harkin. So, the lower the funding level, the----
    Dr. Siliciano. The whole system----
    Senator Harkin [continuing]. The increase in the safety 
factor tends to go up.
    Dr. Siliciano. Yes. So, I don't really think it's a problem 
with the mechanism, I think it's a problem with the funding.
    Senator Harkin. Yeah.
    Yes, Dr. Brugge.
    Dr. Brugge. I completely agree, but I think that, in 
addition, we need visionary leaders, like Dr. Zerhouni was 
pointing out, in terms of the nanotechnology investment. We 
need leaders to be aware of and make opportunities available to 
those individuals that are at the forefront. Because often, as 
you mentioned, they're--these people are--can't really be 
evaluated appropriately by the standing committees. So, for 
instance, if there's technology that is at the interface 
between biology and engineering, there's not really a great 
place--I mean, there is now, but there--initially, there wasn't 
a place for those grants to be reviewed. So, I think it--we do 
have to have extraordinary opportunity kind of funds available 
for the leadership at NIH and the other institutes to have RFAs 
in those areas so that they--we will be able to bring new ideas 
and new--or kind of force new--considering new options.
    Senator Harkin. Well, we had said, when we added that 
money, that $647 million in the continuing resolution, that 
some of that would be used for high-risk, high-impact research. 
Dr. Zerhouni has already announced those awards. New Innovators 
Awards. So, he's already taken that step--Dr. Zerhouni's 
already taken that step, and I just--but I--you know, we've 
often wrestled with this, over a long period of time.
    Dr. Brugge. In our department of Cell Biology, our chairman 
felt very strongly that we needed better technology expertise 
in the Department, and so, he actually encouraged recruitment 
of technology experts that weren't really cell biologists. They 
would never have been recruited if there was a consensus vote 
on those individuals. But, because a slot was made for those 
individuals both are someone who's doing mass spectroscopy and 
cryoelectron microscopy, they've had more impact in our 
Department in our school than any other investigator. They have 
more collaborative papers with other individuals, and their 
papers are all being published in the very top journals. So, 
again, you need visionary leaders to be able to highlight those 
types of individuals and that type of science, and bring them 
in, because--because of the issues that you raised, in terms of 
people being just comfortable where they are.
    Senator Harkin. Dr. Brugge, your statement was something I 
had not focused on, sort of went by me. When we're talking 
about the 20 percent that, for the first submission, it's about 
10 percent. Is that factual now, that about----
    Dr. Brugge. So, if you look at the chart over here--this 
was a chart that was just provided to me by Dr. Neiderhuber, 
the director of the National Cancer Institute. If you look at 
the yellow curve, which might be difficult to see--I asked him 
to specifically give me data on first submission, so all that 
data is on first submission--and then, to break it down into 
competing renewals versus new applications from either new 
investigators or established investigators. If you look at the 
yellow line, those are for competing renewals. Those are for 
teams that are already in place.
    Senator Harkin. Okay.
    Dr. Brugge. Over the long haul, they've been in the range 
of 45 to 50 percent, but, as you can see, since 2003, there's 
just a precipitous drop. So, that shows that 80 percent of 
established investigators that are asking for renewing their 
team's efforts are being turned down on the first submission.
    Senator Harkin. So, that's down----
    Dr. Brugge. And----
    Senator Harkin. But that's 20 percent.
    Dr. Brugge. Twenty percent are being funded, 80----
    Senator Harkin. Right.
    Dr. Brugge [continuing]. Percent are being rejected.
    Senator Harkin. Rejected. But you said for first 
submissions, though, it's 90/10.
    Dr. Brugge. Okay. So, 90/10 is the overall success rate for 
any one cycle. So, that's a combination of the established 
investigators and the new investigators. So, as you can see, 
the new investigators are down to around 5 percent. So, the--
overall 10 percent. So, for instance, NCI is funding new--or 
first awards from competing renewals at some--wait a minute. 
Okay. Maybe somebody from NCI can help with this, because it's 
a little complicated.
    Senator Harkin. Let me see if I can--ask it this way. Okay. 
So, if you take all of the first, second, third submissions and 
all that--so, what's the success rate? Approximately.
    Dr. Brugge. Success rate----
    Senator Harkin. Add'em all up, and then----
    Dr. Brugge. 20 percent.
    Senator Harkin. That's 20 percent. Take out second, third--
you want first submissions. This is the first time they've 
submitted it.
    Dr. Brugge. Yes. Submitted, but it could be a competitive 
renewal.
    Senator Harkin. Competitive renewal.
    Dr. Brugge. It's a--you know, every 5--every 4 or 5 years, 
you have to----
    Senator Harkin. You have to get it renewed, right.
    Dr. Brugge [continuing]. Get renewed. So, it could be the 
first submission of a competitive renewal.
    Senator Harkin. Does anyone know, or maybe Dr. Zerhouni 
could provide it for us--what would the success rate be just 
for first submissions? I don't mean renewals. I mean just for 
the first.

                            NIH SUCCESS RATE

    Dr. Brugge. Oh. That's 5 percent.
    Senator Harkin. Oh, it's 5 percent.
    Dr. Zerhouni. The success rate on first submissions, 
whether you're established or new----
    Senator Harkin. I'm going to ask Dr. Zerhouni to take a 
microphone.
    Dr. Zerhouni. Dr. Brugge is right. If you come in with a 
new grant, the average success rate on the first submission is 
10 percent. But if you are an established investigator, it's 
more like 17 percent.
    Senator Harkin. Yes.
    Dr. Zerhouni. If you're a completely new investigator, it's 
more like 5 percent. So, on average, it's 10 percent; but it's 
much worse for a new investigator versus a new application from 
an established investigator. But, on the average, 90 percent at 
the first submission will have to go back and resubmit again 
and work on finding--on reapplying.
    Senator Harkin. I always thought that it was higher than 
that. I don't know why I thought----
    Dr. Zerhouni. Right. What it is, is this, is that Dr. 
Brugge's talking about the first time that you submit a 
request----
    Senator Harkin. Right.
    Dr. Zerhouni [continuing]. Your chances of being funded, if 
you're a new investigator--and this is why we really thank you 
for the support of new investigators--is between 5 and 7 
percent.
    Senator Harkin. Now, has that been true for a long time?
    Dr. Zerhouni. No, it has been true for the past 2-3 years.
    Senator Harkin. Okay. Good. What was it, back in the 
1980s--late 1980s, early 1990s, in those areas? What happened 
when we doubled the funding?
    Dr. Zerhouni. So, when you doubled the funding, the average 
success rate overall was about 30 percent. If you look at the 
statistics, you can see that the success rate for a new 
investigator was around 15 percent, and the success rate for an 
established investigator was around 40 percent. The two, 
together, made about 30 percent.
    Senator Harkin. So, can I--is this a correct statement I'm 
about to make, that--when we finished the doubling, or during 
that doubling, that first submissions of--first submissions--
not renewals, first submissions--the approval rate would have 
been three times higher than it is right now--15 versus 5?
    Dr. Zerhouni. It would have been three times higher for a 
new investigator.
    Senator Harkin. Yes.
    Dr. Zerhouni. About twice as high for an established 
investigator.
    Senator Harkin. That's it. That--now I understand it. Hmm. 
Three times.
    Dr. Brugge. That's why there's----
    Senator Harkin. Now, see----
    Dr. Brugge [continuing]. A lot of distress.
    Senator Harkin. Now, here's another problem we get into. 
See, that--so, we double the funding, we get more grants out 
there, but obviously these grants are longer than just 3 or 4 
or 5 years. They come in to get renewed. So, all the new ones 
that we got during the bump-up are now in the system, and they 
get renewed, and the new ones can't get in.
    Dr. Zerhouni. Yes, sir, that's why we----
    Senator Harkin. I'll have to think about this one. I mean--
and how we crack that. I mean, that doesn't seem to me to be 
the right course that we ought to be on. Obviously, the correct 
answer that--we talked about this doubling for a long time 
before we started. One of the reasons was, we had seen, over 
the years, how the number of peer-reviewed applications, the 
approval rate had gone down and down and down. We looked at 
each institute. Some were better than others. Some really got 
bad, way down, 1 in 7, 1 in 8, that kind of thing--1 in 10. The 
idea was to get it back up to the level so that the peer-
reviewed grants would be about where we were, I don't know, 25-
30 years ago. That happened. But we also wanted to make room 
and to encourage this new--what was that word I used? High-
risk/high-impact kind of research to be done. Are we now at the 
point where we did the high-risk/high-impact research maybe on 
a one-shot basis or for a couple of years, but now we're not 
doing it? I mean----
    Dr. Strittmatter. I think that's the point that I was 
trying to make. I think there is that influence, that, during 
the doubling, there was an atmosphere created where people took 
high risks, where things advanced rapidly. We made great 
strides. But the retrenchment, a backward progress in the rate 
of grant funding----
    Senator Harkin. Yeah.
    Dr. Strittmatter [continuing]. Has an enormous--the biggest 
influence is on high-risk research and creativity in science, 
more----
    Senator Harkin. Sure.
    Dr. Strittmatter [continuing]. Than steady advance.
    Senator Harkin. Sure.
    Dr. Strittmatter. Even though--whether it's a 9-percent or 
13-percent net decline in total dollars, the effect on high-
risk research might be much, much greater--5, 10 times decline 
in these kind of crucial experiments.
    Senator Harkin. Yeah, I can understand that.
    Well, I just think, Dr. Zerhouni, we're going to have to 
continue to work on that. On the one hand--I mean, it's both 
valuable. I mean, you don't want to cut off people that are in 
the midst of their research project. I mean, you want to 
continue it on, and you want to let new researchers know that, 
if they do get it, they're not going to be cut off at the knees 
once they just get established. On the other hand, you do want 
to encourage new people coming into the system.
    Well, I think the obvious thing that strikes me is that 
we're simply not on a growth pattern like we ought to be on. We 
have to be on a growth pattern on this, and we're just not. I 
get the sense that a lot of people thought, ``Well, we doubled 
it. Now we don't have to do anything for a long time. We can 
just sort of sit there.'' I have to tell you, I hear that 
around here, you know, ``Well, we gave you all that money once. 
You got all that you've got up there, so quit squawking all the 
time.'' But I don't think they realize that we were just making 
up for lost time, that we needed to keep that line going up.
    Well, I've got a lot of questions I could ask. I don't know 
if Senator Specter is coming back or not right now.
    One other question. You're the correct panel to ask this 
question to. One other thing that I want to get a better handle 
on is undergraduate researchers and training scientists. Now, 
we heard a lot during the doubling that this was going to have 
a ripple effect downward, even--maybe down even into high 
schools, getting more high school students taking science if 
they knew they could really become a scientist and have a 
career as a scientist. So, since I think most of you are all--
you're all college-based, one way or the other--tell me about 
undergraduate researchers and scientists, and how does it look 
to you for the future in actually appealing to these young 
people to take up research and be a research scientist as a 
career? Because these are long-term things. That's another 
thing that people ask me about, ``Well, you know, you don't 
need to do all that. I mean, if you''--it's like you can just 
get a researcher--just get someone to take a little time off of 
their practice, and they can be a researcher for a few months, 
and then they can go back to practice again. So, what's 
happening with undergraduate researchers and budding young 
scientists out there? You're in contact with them all the time. 
On the one hand, is there a desire? Do you find young people 
interested in the life sciences that Dr. Zerhouni talked about, 
this new century of life sciences? Is that interest there? Are 
we responding to that? Just an open--just how you feel about 
it.
    Dr. Iverson. Well, thank you. I'm going to take this one.
    It turns out that there's nothing more transformative in 
science education than undergraduate research. The reason is 
that, in an NIH-funded laboratory doing current state-of-the-
art research, an undergraduate is immersed in an environment 
where they finally understand what's really happening. There's 
no way to convey that in the lecture hall. I try my best. You 
can't.
    Senator Harkin. Interesting.
    Dr. Iverson. I'm here today--as I said, I'm here today 
because of a transformative experience. I was on my way to 
business school, and that event changed my thinking--not 
immediately, but it was because I was doing state-of-the-art 
research, or, you know, I was being exposed to it.
    The way it generally operates is that you have laboratories 
that are set up, you have postdocs and graduate students, and 
undergraduates will come in, and they'll be working along with 
a graduate student or a postdoctoral fellow, be brought along 
slowly. What we hope is that, by the end of their second or 
third year, if they're excited about it, they're going to be 
really doing, with their own hands, research that may have an 
impact.
    Senator Harkin. Yeah.
    Dr. Iverson. There is nothing more transformative than 
this. If we don't take graduate students, we don't have those 
opportunities for undergraduates. I wasn't kidding, we put 
1,000 undergraduates in research opportunities at our 
university. We don't attempt to make 1,000 new scientists out 
of them. Whatever they end up doing, if they go to medical 
school, if they go to law school, if they do anything, they 
will finally understand what we have difficulty conveying in 
the classroom or in the media, and that is: what research is 
all about--the excitement, the difficulties, the real 
ramifications of cutting-edge research. I think that when you 
discuss what happens with grant funding pay lines, you have to 
realize that there's a very simple equation that says: fewer 
research opportunities for investigators translates directly 
into fewer research opportunities for undergraduates, as well 
as graduate students.
    Dr. Siliciano. I think there's another dimension to that, 
and that is that the undergraduates are very perceptive, and 
they see the environment, and they see that no matter how 
exciting the science is and how much fun the research is, if 
the principal investigator spends all of their time applying 
for grants and worrying about funding, that it's not an 
appealing sort of career choice. That's my major worry.
    Senator Harkin. Didn't you have something in your statement 
about how much time it took--or may time--how long it takes 
to--for these application processes?
    Dr. Siliciano. Yeah, I mean, traditionally it took me 30 
percent, and now it's 60 percent.
    Senator Harkin. Yeah. That's a lot of time to take out just 
for filling out paperwork and stuff.
    Dr. Siliciano. Yeah, that's right. There's a lot less time 
to interact with undergraduate students, too----
    Senator Harkin. That's right.
    Dr. Siliciano [continuing]. Which is true--it is very true 
in my case.
    Senator Harkin. Any last things before I call a halt to 
this panel? Anything else that you want to bring up? Senator 
Specter just got the floor, I'm told, so he won't be coming 
back.
    Dr. Iverson. Very briefly. I would like to make one 
comment, and that is----
    Senator Harkin. Yes, sir.
    Dr. Iverson [continuing]. We talk about the increased grant 
pressure almost as a burden, and, in fact, I see it as the 
opposite, it's the success of the doubling that allowed us to 
create so many good ideas, collectively, as a scientific 
community that they just demand to be funded. That's what's 
pushing out the new ideas.
    Senator Harkin. That's good.
    Dr. Iverson. This is not a negative thing, it's a very 
positive thing for American science, and we just need to keep 
up the momentum that we've established now, as well as look 
toward the future with new ideas that are, right now, being 
pushed out.
    Senator Harkin. That was good. I like that a lot.
    Well, listen, we'll close this panel down.
    But now we're going to be having a press conference, with 
some of you, to release this study that was done, ``In Our 
Grasp--Or Slipping Away?'' So, we're going to have a press 
conference here. We'll close this down, and we're going to move 
to a press conference within just a couple of minutes.

                     ADDITIONAL COMMITTEE QUESTIONS

    There will be some additional questions which will be 
submitted for your response in the record.
    [The following questions were not asked at the hearing, but 
were submitted to the Department for response subsequent to the 
hearing:]

               Questions Submitted by Senator Tom Harkin

                               VULVODYNIA

    Question. In fiscal year 2006, the Committee called upon the Office 
of Research on Women's Health to implement a national education program 
for primary care health professionals, patients and the general public 
on vulvodynia's symptoms, diagnosis and treatment options. I commend 
ORWH, under the leadership of Dr. Vivian Pinn, for its work so far to 
develop the campaign. Please provide an update on its current status, 
including a brief summary of its components, expected launch date and 
the resources that have been and will be allocated for this effort. 
Information on the resources should include the amount of funds that 
will be used to publicize the campaign and disseminate materials to the 
lay and professional communities. OD/ORWH
    Answer. The Office of Research on Women's Health (ORWH), National 
Institutes of Health (NIH), Department of Health and Human Services 
(HHS), is developing a national education program for primary care 
health professionals, patients and the general public on vulvodynia's 
symptoms, diagnosis and treatment options. The first step was to 
initiate collaborations with relevant HHS/NIH Institutes and Centers 
(ICs) and key consumer and health care professional organizations 
through several planning meetings convened by the ORWH. Participants in 
on-going discussions include representatives from the National 
Institute of Child Health and Human Development (NICHD) and the 
National Institute of Neurological Disorders and Stroke (NINDS) as well 
as other stakeholders such as the National Vulvodynia Association 
(NVA), the National Women's Health Resource Center (NWHRC), the 
American College of Obstetricians and Gynecologists (ACOG) and 
interested researchers. Other Offices of Women's Health across HHS will 
be invited to become partners in this effort as plans for distribution 
of materials and additional educational efforts are developed.
    A tentative launch date of this educational campaign is planned for 
October 2007. An initial list of documents under development includes a 
new ORWH Vulvodynia Fact Sheet with Questions and Answers (Q&As); a 
vulvodynia resource guide with relevant web site information, such as 
the ORWH web site for vulvodynia at http://orwh.od.nih.gov/health/
vulvodynia.html; reprints of current scientific journal articles on 
vulvodynia, such as Vulvodynia--A State-of-the-Art Consensus on 
Definitions, Diagnosis and Management; and the ACOG Vulvodynia 
Guidelines--A Literature Review. Plans are underway to develop 
additional public outreach materials.
    Parallel with the print material campaign will be the expansion and 
enhancement of the current ORWH vulvodynia web page. NICHD, the 
Institute that provides the majority of NIH funding for vulvodynia 
research, will contribute to the development and implementation of this 
educational effort especially through contributions of the NICHD 
Information Resource Center (IRC), where the materials developed will 
be stored and distributed for target audiences. Additionally, NICHD has 
offered the services of the IRC Information Specialists to answer 
questions in English and Spanish related to vulvodynia both online and 
through a 1-800 telephone line. NICHD also plans to track the labor, 
material, and postage for NIH vulvodynia material so that these costs 
can be documented.
    Focus group testing will occur prior to the launch of the education 
campaign, including creating questions related to the materials for 
focus group testing, locating participants, preparing the group 
logistics, conducting small focus groups, and reviewing and sharing the 
results with the group collaborating in this effort.
    Concurrent with the launch of this educational campaign, ORWH will 
dedicate its monthly podcast, Pinn Point on Women's Health Research, to 
vulvodynia, including an announcement of available materials. The 
podcast will also include interviews and Q&As with vulvodynia research 
experts and appropriate web site references for further information. 
The podcast will be the first step in disseminating the educational 
campaign. Additional plans and activities are under development. ORWH 
and its partners will also send html e-mail announcements to targeted 
organizations announcing the start of the campaign to various 
listserves and other internet outlets, as well as to women's magazine 
editors and other similar consumer oriented media outlets. Radio spots, 
produced by the NIH and widely distributed across the nation's 
airwaves, will also be used to focus on vulvodynia.
    ORWH is developing these materials, resources, and educational 
plans utilizing both budgetary expenditures and in-kind contributions. 
For example, the contributions of the NICHD IRC will be in-kind but 
would ordinarily represent a significant budgetary expenditure for this 
project. In addition, ORWH staff time spent in development of the plan, 
materials and implementation of the project are not included in cost 
estimates.
    Note: This estimate does not include dedicated ORWH staff time, 
NICHD staff time, or other in-kind contributions.

------------------------------------------------------------------------
                                                              Amount
------------------------------------------------------------------------
ORWH Preliminary cost estimate:
    Vulvodynia Information Packet and Materials                   $6,000
     Development........................................
    Reproduction of the vulvodynia information packet            115,000
     and materials (5000 copies)........................
    Development of additional consumer information                30,000
     materials..........................................
    Medical journal reprints............................          25,000
    Logistical support for focus groups and direct                10,000
     distribution of materials..........................
                                                         ---------------
      Total Estimated Cost..............................         186,000
------------------------------------------------------------------------

                          BEHAVIORAL RESEARCH

    Question. Behavior and the environment cause more than 70 percent 
of avoidable deaths, suggesting that many instances of disease can be 
prevented. Furthermore, a recent IOM report called for the conduct of 
transdisciplinary research on the interactions across the genetic, 
behavioral, and social environments. While NIH has made great advances 
in understanding the genomic side of health, are there plans now to 
enhance research on the impact of the behavioral, social, and physical 
environment on health?
    Answer. Building on over 50 years of behavioral and social science 
findings, together with recent advances in understanding genetics, NIH 
is poised to more fully examine the complex interactions between 
genetic mechanisms and environmental factors that lead to disease and 
disability. As noted, the recent Institute of Medicine Report, Genes, 
Behavior, and the Social Environment: Moving Beyond the Nature/Nurture 
Debate, recommends a number of ways to foster the necessary 
transdisciplinary research teams to accomplish this. The NIH's Office 
of Behavioral and Social Sciences Research (OBSSR), located in the 
Office of the Director, is leading the implementation of the 
recommendations produced by this report. Working with several NIH 
Institutes and Centers (ICs), OBSSR is currently developing an 
initiative to supplement ongoing research to allow for the addition of 
social environmental information to genetic studies and/or the addition 
of genomic information to behavioral and social science research 
projects. OBSSR has set aside $3 million in fiscal year 2008 for the 
funding of this initiative and is requesting funding contributions from 
the participating ICs.
    OBSSR also is planning an annual genomics training institute for 
behavioral and social scientists. This course will cover basic concepts 
and methods of genomics research to better enable these investigators 
to integrate behavioral, social, and physical environmental factors 
into genomics research and thereby work more effectively with their 
genomics and biomedical colleagues.
    In February 2006, Secretary Mike Leavitt announced the trans-NIH 
Genes, Environment and Health Initiative (GEI), designed to combine 
genetic analysis and environmental technology development to better 
understand the causes of common diseases. As a first step toward 
implementing large scale gene and environment interaction studies, a 
need was identified to invest in the development and improvement of 
tools to assess individual exposures to environmental factors and to 
identify biomarkers which characterize the response of these exposures 
on key biological pathways. OBSSR and other IC staff have been leading 
the effort to include social and behavioral research in this effort, 
resulting in research funding announcements calling for the development 
of measures of diet and physical activity (RFA-CA-07-032) and 
psychosocial stress and addictive substances (RFA-DA-07-005).
    These activities are examples of recent efforts to stimulate 
research at the interface of genetics and the behavioral/social 
sciences that will ultimately allow us to examine how interactions 
between our genes and our environments, broadly defined to include the 
physical, chemical, behavioral and social environments, influence 
health. Nearly all ICs support investigator-initiated behavioral and 
social science research; they also issue funding opportunity 
announcements to solicit research applications on particular topics, 
often in partnership with each other and with OBSSR. Total NIH funding 
for behavioral and social science research is estimated at 
approximately $3 billion annually since fiscal year 2004, roughly 10 
percent of the entire NIH budget.

                         TRANSLATIONAL RESEARCH

    Question. It takes years for research discoveries to reach the 
population at large, suggesting a significant gap in translational 
research. Translation of research takes place across two phases: from 
bench to bedside and from bedside to the population at large. What 
percentage of the NIH budget supports translational research overall, 
and how much is spent on each of the two phases?
    Answer. Presently, NIH does not collect funding levels for 
translational research. However, we do report funding levels for 
clinical research, and for the current year (fiscal year 2007) and the 
budget year (fiscal year 2008), we estimate $8.8 billion will be spent 
on this research category.
                                 ______
                                 
              Questions Submitted by Senator Arlen Specter

                        REVISED MECHANISM TABLE

    Question. The fiscal year 2007 enacted level provided NIH with 
increased funding that was not envisioned in the fiscal year 2008 
Budget submission. It also requires NIH to submit a revised fiscal year 
2007 operating plan. We realize increase funding in one year can impact 
the following year's distribution of competing grants and mechanisms. 
Therefore, please submit for the record a revised mechanism table that 
shows the impact of the fiscal year 2007 enacted level on the fiscal 
year 2008 President's Budget request. Also, please revise and submit 
any of the data in the ``Tabular Data'' section of NIH's Volume I 
Overview section of the CJ that changes to reflect the adjustments to 
fiscal year 2007 enacted level and its impact on the fiscal year 2008 
Budget Request.
    Answer. The requested revised ``Tabular Data'' section follows, 
which includes the NIH total mechanism display.

                                                       FISCAL YEAR 2006 APPROPRIATION ADJUSTMENTS
                                                                [In thousands of dollars]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                           Cong. action                                              Real transfers
                                    --------------------------             -----------------------------------------------------------------
                                            Fiscal year          Subtotal                                                                     Subtotal,
                 IC                 --------------------------    cong.                                                          Director's     Pres.
                                                    2006  1       action    Global AIDS      HHS       Adv. dev.      NIH RM     1 percent      budget
                                         2006       percent                   transfer     transfer     transfer     transfer     transfer     appendix
                                      conference   rescission
--------------------------------------------------------------------------------------------------------------------------------------------------------
NCI................................    4,841,774      -48,418    4,793,356  ...........       -3,293  ...........      -42,834  ...........    4,747,229
NHLBI..............................    2,951,270      -29,513    2,921,757  ...........       -2,007  ...........      -26,109  ...........    2,893,641
NIDCR..............................      393,269       -3,933      389,336  ...........         -267  ...........       -3,479  ...........      385,590
NIDDK..............................    1,722,146      -17,221    1,704,925  ...........       -1,172  ...........      -15,236  ...........    1,688,517
NINDS..............................    1,550,260      -15,503    1,534,757  ...........       -1,054  ...........      -13,715  ...........    1,519,988
NIAID..............................    4,459,395      -44,594    4,414,801      -99,000       -3,033      -49,500      -38,567  ...........    4,224,701
NIGMS..............................    1,955,170      -19,552    1,935,618  ...........       -1,330  ...........      -17,297  ...........    1,916,991
NICHD..............................    1,277,544      -12,775    1,264,769  ...........         -869  ...........      -11,302  ...........    1,252,598
NEI................................      673,491       -6,735      666,756  ...........         -458  ...........       -5,958  ...........      660,340
NIEHS..............................      647,608       -6,476      641,132  ...........         -440  ...........       -5,729       -4,480      630,483
NIA................................    1,057,203      -10,572    1,046,631  ...........         -719  ...........       -9,353  ...........    1,036,559
NIAMS..............................      513,063       -5,131      507,932  ...........         -349  ...........       -4,539  ...........      503,044
NIDCD..............................      397,432       -3,974      393,458  ...........         -270  ...........       -3,516  ...........      389,672
NIMH...............................    1,417,692      -14,177    1,403,515  ...........         -964  ...........      -12,542  ...........    1,390,009
NIDA...............................    1,010,130      -10,101    1,000,029  ...........         -687  ...........       -8,937  ...........      990,405
NIAAA..............................      440,333       -4,403      435,930  ...........         -300  ...........       -3,896  ...........      431,734
NINR...............................      138,729       -1,387      137,342  ...........          -94  ...........       -1,227  ...........      136,021
NHGRI..............................      490,959       -4,910      486,049  ...........         -334  ...........       -4,343  ...........      481,372
NIBIB..............................      299,808       -2,998      296,810  ...........         -204  ...........       -2,652  ...........      293,954
NCRR...............................    1,110,203      -11,102    1,099,101  ...........         -755  ...........       -9,822  ...........    1,088,524
NCCAM..............................      122,692       -1,227      121,465  ...........          -83  ...........       -1,086  ...........      120,296
NCMHD..............................      197,379       -1,974      195,405  ...........         -134  ...........       -1,746  ...........      193,525
FIC................................       67,048         -670       66,378  ...........          -46  ...........         -593  ...........       65,739
NLM................................      318,091       -3,181      314,910  ...........         -216  ...........       -2,814  ...........      311,880
OD.................................      482,895       -4,829      478,066  ...........         -328  ...........      247,292  ...........      725,030
B&F................................       81,900         -819       81,081  ...........          -56  ...........  ...........        4,480       85,505
                                    --------------------------------------------------------------------------------------------------------------------
Total NIH..........................   28,617,484     -286,175   28,331,309      -99,000      -19,462      -49,500  ...........  ...........   28,163,347
Superfund..........................       80,289       -1,181       79,108  ...........  ...........  ...........  ...........  ...........       79,108
                                    --------------------------------------------------------------------------------------------------------------------
      Ttl,w/Supfnd.................   28,697,773     -287,356   28,410,417      -99,000      -19,462      -49,500  ...........  ...........   28,242,455
--------------------------------------------------------------------------------------------------------------------------------------------------------


------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                      HHS comp. transfers       NIH comp. transfers                                     Prog. level
                                                  ----------------------------------------------------    Other       Subtotal  --------------------------   Subtotal    Other NIH     Subtotal
                        IC                         PHSSEF pan.   Other HHS     Roadmap     Other NIH   global AIDS   HHS budg.      Type 1      NLM PHS     HHS table      oblig.       NIH CJ
                                                       flu       transfers    comparable   transfers                   auth.       diabetes      eval.     prog. level    adjust.       table
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
NCI..............................................  ...........          -14       42,834       -1,872  ...........    4,788,177  ...........  ...........    4,788,177        6,896    4,795,073
NHLBI............................................  ...........           -3       26,109       -3,824  ...........    2,915,923  ...........  ...........    2,915,923  ...........    2,915,923
NIDCR............................................  ...........           -1        3,479         -404  ...........      388,664  ...........  ...........      388,664  ...........      388,664
NIDDK............................................  ...........           -3       15,236         -601  ...........    1,703,149      150,000  ...........    1,853,149  ...........    1,853,149
NINDS............................................  ...........           -3       13,715         -655  ...........    1,533,045  ...........  ...........    1,533,045  ...........    1,533,045
NIAID............................................       18,000           -9       38,567       -1,060       99,000    4,379,199  ...........  ...........    4,379,199  ...........    4,379,199
NIGMS............................................  ...........           -1       17,297         -244  ...........    1,934,043  ...........  ...........    1,934,043  ...........    1,934,043
NICHD............................................  ...........           -4       11,302         -375  ...........    1,263,521  ...........  ...........    1,263,521  ...........    1,263,521
NEI..............................................  ...........           -1        5,958         -529  ...........      665,768  ...........  ...........      665,768  ...........      665,768
NIEHS............................................  ...........           -4        5,729         -213  ...........      635,995  ...........  ...........      635,995  ...........      635,995
NIA..............................................  ...........           -3        9,353         -708  ...........    1,045,201  ...........  ...........    1,045,201  ...........    1,045,201
NIAMS............................................  ...........           -1        4,539         -166  ...........      507,416  ...........  ...........      507,416  ...........      507,416
NIDCD............................................  ...........           -1        3,516          -76  ...........      393,111  ...........  ...........      393,111  ...........      393,111
NIMH.............................................  ...........           -3       12,542         -735  ...........    1,401,813  ...........  ...........    1,401,813  ...........    1,401,813
NIDA.............................................  ...........           -2        8,937         -482  ...........      998,858  ...........  ...........      998,858  ...........      998,858
NIAAA............................................  ...........           -1        3,896         -150  ...........      435,479  ...........  ...........      435,479  ...........      435,479
NINR.............................................  ...........  ...........        1,227          -98  ...........      137,150  ...........  ...........      137,150  ...........      137,150
NHGRI............................................  ...........           -2        4,343          -58  ...........      485,655  ...........  ...........      485,655  ...........      485,655
NIBIB............................................  ...........  ...........        2,652        1,482  ...........      298,088  ...........  ...........      298,088  ...........      298,088
NCRR.............................................  ...........  ...........        9,822       10,601  ...........    1,108,947  ...........  ...........    1,108,947  ...........    1,108,947
NCCAM............................................  ...........  ...........        1,086         -248  ...........      121,134  ...........  ...........      121,134  ...........      121,134
NCMHD............................................  ...........  ...........        1,746           -8  ...........      195,263  ...........  ...........      195,263  ...........      195,263
FIC..............................................  ...........  ...........          593          -15  ...........       66,317  ...........  ...........       66,317  ...........       66,317
NLM..............................................  ...........         -484        2,814         -133  ...........      314,077  ...........        8,200      322,277            1      322,278
OD...............................................  ...........           -2     -247,292          571  ...........      478,307  ...........  ...........      478,307  ...........      478,307
B&F..............................................  ...........  ...........  ...........  ...........  ...........       85,505  ...........  ...........       85,505  ...........       85,505
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
Total NIH........................................       18,000         -542  ...........  ...........       99,000   28,279,805      150,000        8,200   28,438,005        6,897   28,444,902
Superfund........................................  ...........  ...........  ...........  ...........  ...........       79,108  ...........  ...........       79,108  ...........       79,108
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      Ttl,w/Supfnd...............................       18,000         -542  ...........  ...........       99,000   28,358,913      150,000        8,200   28,517,113        6,897   28,524,010
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------


                                                  FISCAL YEAR 2007 ADJUSTMENTS--JOINT RESOLUTION LEVEL
                                                                [In thousands of dollars]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                     Comp.      Subtotal,                                                 Prog. level
                                        Joint        trnsf.       Pres.      Other HHS    NIH comp.    Subtotal,  --------------------------  Subtotal,
                 IC                   resolution    advanced      budget     transfers    transfers    HHS budg.      Type I      NLM PHS     HHS prog.
                                                      dev.       appendix                                auth.       diabetes      Eval.        level
--------------------------------------------------------------------------------------------------------------------------------------------------------
NCI................................   $4,797,639  ...........   $4,797,639         -$14      -$2,134   $4,795,491  ...........  ...........   $4,795,491
NHLBI..............................    2,922,929  ...........    2,922,929           -3       -2,946    2,919,980  ...........  ...........    2,919,980
NIDCR..............................      389,703  ...........      389,703           -1         -332      389,370  ...........  ...........      389,370
NIDDK..............................    1,705,868  ...........    1,705,868           -3         -639    1,705,226     $150,000  ...........    1,855,226
NINDS..............................    1,535,545  ...........    1,535,545           -3         -638    1,534,904  ...........  ...........    1,534,904
NIAID..............................    4,417,208     -$49,500    4,367,708           -9       -1,254    4,366,445  ...........  ...........    4,366,445
NIGMS..............................    1,935,808  ...........    1,935,808           -1         -182    1,935,625  ...........  ...........    1,935,625
NICHD..............................    1,254,707  ...........    1,254,707           -4         -559    1,254,144  ...........  ...........    1,254,144
NEI................................      667,116  ...........      667,116           -1         -440      666,675  ...........  ...........      666,675
NIEHS..............................      642,002  ...........      642,002           -4         -225      641,773  ...........  ...........      641,773
NIA................................    1,047,260  ...........    1,047,260           -3         -757    1,046,500  ...........  ...........    1,046,500
NIAMS..............................      508,240  ...........      508,240           -1         -179      508,060  ...........  ...........      508,060
NIDCD..............................      393,668  ...........      393,668           -1         -127      393,540  ...........  ...........      393,540
NIMH...............................    1,404,494  ...........    1,404,494           -3         -921    1,403,570  ...........  ...........    1,403,570
NIDA...............................    1,000,621  ...........    1,000,621           -2         -605    1,000,014  ...........  ...........    1,000,014
NIAAA..............................      436,259  ...........      436,259           -1         -201      436,057  ...........  ...........      436,057
NINR...............................      137,404  ...........      137,404  ...........         -117      137,287  ...........  ...........      137,287
NHGRI..............................      486,491  ...........      486,491           -2          -62      486,427  ...........  ...........      486,427
NIBIB..............................      296,887  ...........      296,887  ...........        1,504      298,391  ...........  ...........      298,391
NCRR...............................    1,133,240  ...........    1,133,240  ...........       10,601    1,143,841  ...........  ...........    1,143,841
NCCAM..............................      121,576  ...........      121,576  ...........         -197      121,379  ...........  ...........      121,379
NCMHD..............................      199,444  ...........      199,444  ...........          -15      199,429  ...........  ...........      199,429
FIC................................       66,446  ...........       66,446  ...........          -24       66,422  ...........  ...........       66,422
NLM................................      320,850  ...........      320,850         -484         -137      320,229  ...........       $8,200      328,429
OD.................................    1,096,401  ...........    1,096,401           -2          586    1,096,985  ...........  ...........    1,096,985
B&F................................       81,081  ...........       81,081  ...........  ...........       81,081  ...........  ...........       81,081
                                    --------------------------------------------------------------------------------------------------------------------
      Total NIH....................   28,998,887      -49,500   28,949,387         -542  ...........   28,948,845      150,000        8,200   29,107,045
Superfund..........................       79,117  ...........       79,117  ...........  ...........       79,117  ...........  ...........       79,117
                                    --------------------------------------------------------------------------------------------------------------------
      Total, w/Supfnd..............   29,078,004      -49,500   29,028,504         -542  ...........   29,027,962      150,000        8,200   29,186,162
--------------------------------------------------------------------------------------------------------------------------------------------------------


                                                       FISCAL YEAR 2008 PRESIDET'S BUDGET REQUEST
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                    Fiscal year
                                                          ----------------------------------------------------------------------------------------------
                      Appropriation                         2006  actual \1\   2007 Presidet's       2007 joint                          2008 Est. +/-
                                                            \2\ \3\ \4\ \5\     budget \1\ \3\     resolution \1\    2008  Presidet's      2007 joint
                                                                  \6\            \4\ \5\ \6\      \3\ \4\ \5\ \6\       budget \1\         resolution
--------------------------------------------------------------------------------------------------------------------------------------------------------
NCI......................................................     $4,795,073,000     $4,751,461,000     $4,795,491,000     $4,782,114,000       -$13,377,000
NHLBI....................................................      2,915,923,000      2,898,063,000      2,919,980,000      2,925,413,000         +5,433,000
NIDCR....................................................        388,664,000        385,762,000        389,370,000        389,722,000           +352,000
NIDDK \7\................................................      1,853,149,000      1,843,656,000      1,855,226,000      1,858,045,000         +2,819,000
NINDS....................................................      1,533,045,000      1,524,109,000      1,534,904,000      1,537,019,000         +2,115,000
NIAID....................................................            \8\ \9\      4,394,233,000  \9\ 4,366,445,000      4,592,482,000       +226,037,000
                                                               4,379,199,000
NIGMS....................................................      1,934,043,000      1,923,298,000      1,935,625,000      1,941,462,000         +5,837,000
NICHD....................................................      1,263,521,000      1,256,855,000      1,254,144,000      1,264,946,000        +10,802,000
NEI......................................................        665,768,000        660,917,000        666,675,000        667,820,000         +1,145,000
NIEHS....................................................   \10\ 635,995,000        637,094,000        641,773,000        637,406,000         -4,367,000
NIA......................................................      1,045,201,000      1,039,068,000      1,046,500,000      1,047,148,000           +648,000
NIAMS....................................................        507,416,000        504,353,000        508,060,000        508,082,000            +22,000
NIDCD....................................................        393,111,000        391,428,000        393,540,000        393,682,000           +142,000
NIMH.....................................................      1,401,813,000      1,393,882,000      1,403,570,000      1,405,421,000         +1,851,000
NIDA.....................................................        998,858,000        994,222,000      1,000,014,000      1,000,365,000           +351,000
NIAAA....................................................        435,479,000        433,116,000        436,057,000        436,505,000           +448,000
NINR.....................................................        137,150,000        136,433,000        137,287,000        137,800,000           +513,000
NHGRI....................................................        485,655,000        482,878,000        486,427,000        484,436,000         -1,991,000
NIBIB....................................................        298,088,000        296,354,000        298,391,000        300,463,000         +2,072,000
NCRR.....................................................      1,108,947,000      1,108,843,000      1,143,841,000      1,112,498,000        -31,343,000
NCCAM....................................................        121,134,000        120,357,000        121,379,000        121,699,000           +320,000
NCMHD....................................................        195,263,000        194,284,000        199,429,000        194,495,000         -4,934,000
FIC......................................................         66,317,000         66,657,000         66,422,000         66,594,000           +172,000
NLM \12\.................................................        314,078,000        312,648,000        320,229,000        312,562,000         -7,667,000
OD \13\..................................................        478,307,000   \11\ 508,909,000      1,096,985,000        517,062,000       -579,923,000
B&F......................................................    \10\ 85,505,000         81,081,000         81,081,000        136,000,000        +54,919,000
Type 1 Diabetes..........................................       -150,000,000       -150,000,000       -150,000,000       -150,000,000  .................
                                                          ----------------------------------------------------------------------------------------------
      Subtotal, Labor/HHS................................     28,286,702,000     28,189,961,000     28,948,845,000     28,621,241,000       -327,604,000
Interior/Superfund Research Program......................         79,108,000         78,414,000         79,117,000         78,434,000           -683,000
                                                          ----------------------------------------------------------------------------------------------
      Total, NIH Discretioary B.A........................     28,365,810,000     28,268,375,000     29,027,962,000     28,699,675,000       -328,287,000
Type 1 Diabetes \7\......................................        150,000,000        150,000,000        150,000,000        150,000,000  .................
                                                          ----------------------------------------------------------------------------------------------
      Total, NIH Budget Authority........................     28,515,810,000     28,418,375,000     29,177,962,000     28,849,675,000       -328,287,000
NLM Program Evaluation...................................          8,200,000          8,200,000          8,200,000          8,200,000  .................
                                                          ----------------------------------------------------------------------------------------------
      Total, Prog. Level.................................     28,524,010,000     28,426,575,000     29,186,162,000     28,857,875,000       -328,287,000

--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Includes funds to be transferred to the Global Fund for HIV/AIDS, Malaria, and Tuberculosis (fiscal year 2006--$99,000,000; fiscal year 2007 PB--
  $100,000,000; fiscal year 2007 Annualized--$99,000,000; fiscal year 2008-- $300,000,000).
\2\ Includes Government-wide 1 percent rescission and HHS 1 percent transfer.
\3\ Comparable for ASAM and ASPA transfer--$62,000.
\4\ Comparable for DBEPS program transfer to NIBIB (fiscal year 2006--$1,496,000; fiscal year 2007--$1,528,000).
\5\ Comparable for CIO transfer to OD (fiscal year 2006--$641,000; fiscal year 2007--$669,000).
\6\ Comparable for K-30 transfer to NCRR ($10,613,000).
\7\ Includes funds for the Type 1 Diabetes Initiative.
\8\ NIAID includes $18,000,000 for Pandemic Influenza from PHSSEF.
\9\ Comparable for transfer of Advance Development Fund to ASPR (-$49,500,000).
\10\ Directors 1 percent transfer NIEHS to B&F ($4,480,000).
\11\ OD comparable (-$159,500,000) to ASPR for Advance Development Fund.
\12\ Comparable for transfer to DHHS for PHS Historian ($480,000).
\13\ Total OD includes Roadmap funds for fiscal year 2006 of $82,170,000; fiscal year 2007 PB of $110,700,000; fiscal year 2007 Annualized Current Rate
  of $82,170; fiscal year 2008 of $121,540,000.


                                                                                     BUDGET MECHANISM--TOTAL
                                                                                     [Dollars in thousands]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                            Fiscal year                                                              Change
                                        ----------------------------------------------------------------------------------------------------------------------------------------------  Percent
               MECHANISM                       2006 actual \1\        2007 revised Pres. budget     2007 joint resolution            2008 estimate                                       change
                                        ------------------------------------------------------------------------------------------------------------------     No          Amount        amount
                                             No          Amount          No          Amount          No          Amount           No          Amount
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
            Research Grants

Research Projects:
    Noncompeting.......................    27,366      $11,070,308     26,669      $11,063,137     26,668       $10,896,993     26,573       $10,975,609        -95          $78,616       0.7
    Administrative supplements.........    (1,678)         284,083     (1,254)         145,687     (1,463)          177,707     (1,543)          204,463        (80)          26,756      15.1
    Competing..........................     9,129        3,361,827      9,290        3,384,714     10,154         3,731,558      9,404         3,293,817       (750)        -437,741     -11.7
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal, RPGs...................    36,495       14,716,218     35,959       14,593,538     36,822        14,806,258     35,977        14,473,889       -845         -332,369       2.2
SBIR/STTR..............................     1,822          616,779      1,829          605,284      1,807           610,998      1,793           606,930        -14           -4,068      -0.7
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal, RPGs...................    38,317       15,332,997     37,788       15,198,822     38,629        15,417,256     37,770        15,080,819       -859         -336,437       2.2
                                        ========================================================================================================================================================
Research Centers:
    Specialized/comprehensive..........     1,190        2,144,310      1,104        2,147,862      1,114         2,196,970      1,108         2,198,277         -6            1,307       0.1
    Clinical research..................        93          348,476        295          375,986         95           386,898         89           419,123         -6           32,225       8.3
    Biotechnology......................       103          134,862        113          133,797        113           134,345        111           130,550         -2           -3,795      -2.8
      Comparative medicine.............        51          123,032         49          122,294         49           123,019         47           117,735         -2           -5,284      -4.3
    Research Centers in Minority               28           54,213         28           53,289         28            53,819         27            51,727         -1           -2,092      -3.9
     Institutions......................
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal, Centers................     1,465        2,804,893      1,589        2,833,228      1,399         2,895,051      1,382         2,917,412        -17           22,361       0.8
                                        ========================================================================================================================================================
Other Research:
    Research careers...................     4,192          644,693      4,322          674,060      4,425           693,226      4,540           700,715        115            7,489       1.1
    Cancer education...................        99           34,561         99           34,406        102            35,406        103            35,806          1              400       1.1
    Cooperative clinical research......       353          344,503        351          344,249        368           353,445        364           354,580         -4            1,135       0.3
    Biomedical research support........       140           65,518        139           64,312        212            98,312        139            61,745        -73          -36,567     -37.25
    Minority biomedical research              155          115,032        151          114,470        149           113,810        158           112,630          9           -1,180      -1.0
     support...........................
    Other..............................     1,685          465,044      1,648          469,711      1,722           473,598      1,708           481,691        -14            8,093       1.7
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal, Other Research.........     6,624        1,669,351      6,710        1,701,208      6,978         1,767,797      7,012         1,747,167         34          -20,630      -1.2
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Total Research Grants............    46,406       19,807,241     46,087       19,733,258     47,006        20,080,104     46,164        19,745,398       -842         -334,706      -1.7
                                        ========================================================================================================================================================
Ruth L. Kirschstein Training Awards:
    Individual awards..................  \2\ 2,976         122,758   \2\ 2,995         124,192   \2\ 3,081          127,983   \2\ 3,078          127,728         -3             -255      -0.2
    Institutional awards...............  \2\ 14,34         625,883   \2\ 14,46         631,604   \2\ 14,66          643,617   \2\ 14,58          641,685        -80           -1,932      -0.3
                                                9                           1                           3                            3
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Total, Training..................  \2\ 17,32         748,641   \2\ 17,45         755,796   \2\ 17,74          771,600   \2\ 17,66          769,413        -83           -2,187      -0.3
                                                5                           6                           4                            1
                                        ========================================================================================================================================================
Research & development contracts.......     3,423        2,667,066      3,460        2,652,882      3,529         2,783,528      3,552         2,975,285         23          191,757       6.9
    (SBIR/STTR)........................       (92)         (23,809)       (98)         (24,504)      (110)          (30,027)      (110)          (29,996)  .........            (-31)     -0.1
Intramural research....................  .........       2,772,036   .........       2,751,751   .........        2,791,706   .........        2,774,311   .........         -17,395      -0.6
Research management and support........  .........       1,108,615   .........       1,122,498   .........        1,132,127   .........        1,142,492   .........          10,365       0.9
Cancer prevention & control............  .........         505,705   .........         502,700   .........          516,565   .........          516,565   .........  ...............  .........
Extramural Construction................  .........          29,700   .........          25,000   .........  ................  .........  ................  .........  ...............  .........
Library of Medicine....................  .........         311,264   .........         308,866   .........          320,229   .........          308,415   .........         -11,814      -3.7
    (Appropriation)....................  .........        (314,078)  .........        (312,648)  .........         (320,229)  .........         (312,562)  .........         (-7,667)     -2.4
Office of the Director.................  .........         393,009   .........         398,209   .........          613,985   .........          395,522   .........        -218,463     -35.6
    (Appropriation)....................  .........        (478,307)  .........        (508,909)  .........       (1,096,985)  .........         (517,062)  .........       (-579,923)    -52.9
Buildings and Facilities \3\...........  .........          93,425   .........          89,001   .........           89,001   .........          143,840   .........          54,839      61.6
    (Appropriation)....................  .........         (85,505)  .........         (81,081)  .........          (81,081)  .........         (136,000)  .........         (54,919)     67.7
NIH Roadmap for Medical Research \4\...  .........        (332,590)  .........        (442,673)  .........         (483,000)  .........         (486,153)  .........          (3,153)      0.7
Type 1 Diabetes \5\....................  .........        -150,000   .........        -150,000   .........         -150,000   .........         -150,000   .........  ...............  .........
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal, Labor/HHS Budget         .........      28,286,702   .........      28,189,961   .........       28,948,845   .........       28,621,241   .........        -327,604      -1.1
       Authority.......................
Interior Appropriation for Superfund     .........          79,108   .........          78,414   .........           79,117   .........           78,434   .........            -683      -0.9
 Res...................................
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Total, NIH Discretionary B.A.....  .........      28,365,810   .........      28,268,375   .........       29,027,962   .........       28,699,675   .........        -328,287      -1.1
Type 1 Diabetes \5\....................  .........         150,000   .........         150,000   .........          150,000   .........          150,000   .........  ...............  .........
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Total, NIH Budget Authority......  .........      28,515,810   .........      28,418,375   .........       29,177,962   .........       28,849,675   .........        -328,287      -1.1
NLM Program Evaluation.................  .........           8,200   .........           8,200   .........            8,200   .........            8,200   .........  ...............  .........
                                        --------------------------------------------------------------------------------------------------------------------------------------------------------
      Total, Program Level.............  .........      28,524,010   .........      28,426,575   .........       29,186,162   .........       28,857,875   .........        -328,287      -1.1
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Budget Authority 2006 total includes mechanism distribution of NCI breast cancer stamp funds of $6,896.
\2\ FTTPs.
\3\ Includes the B&F appropriation plus the following included in NCI--fiscal year 2006: $7,920; fiscal year 2007: $7,920; fiscal year 2008: $7,840.
\4\ Included in above mechanisms. Roadmap contributions from the NLM and OD are reflected in the mechanisms of award.
\5\ Included in NIDDK--fiscal year 2006: $150,000; fiscal year 2007: $150,000; fiscal year 2008: $150,000.
Numbers of grants identified in fiscal year 2007 and fiscal year 2008 are estimates, and WILL change as applications are received and selected for funding.
Fiscal year 2006 and fiscal year 2007 have been adjusted to display comparably proposed program changes in fiscal year 2008. The fiscal year 2008 President's Budget Appendix reflects an actual
  fiscal year 2006 budget authority total of $28,242 million, a difference of $282 million from the fiscal year 2006 program level reported above. fiscal year 2006 adjustments to the Budget
  Appendix include the addition of Special Statutory Type I Diabetes Funds +$150M); a transfer from the PHSSEF for Pandemic Influenza activities (+$18M); a comparable adjustment for the Global
  Fund for HIV/AIDS actual transfer (+$99M); revenue from the Breast Cancer Stamp (+$7M);and use of the Secretary's evaluation funds transfer authority for NLM (+$8M). The fiscal year 2007
  budget authority in the fiscal year 2008 Budget Appendix is $28,450 million, a difference of $736 million from the fiscal year 2007 Joint Resolution program level reported above. In addition
  to increases provided by the fiscal year 2007 Joint Resolution, fiscal year 2007 program level adjustments include the addition of Special Statutory Type I Diabetes Funds (+$150M); and use
  of the Secretary's evaluation funds transfer authority for NLM (+$8M).


                  FISCAL YEAR 2008 SPECIAL INITIATIVES
                        [In thousands of dollars]
------------------------------------------------------------------------
                                            Pathway to
                                           independence        CTSA
------------------------------------------------------------------------
NCI.....................................           1,800  ..............
NHLBI...................................           1,980  ..............
NIDCR...................................             540  ..............
NIDDK...................................           1,080  ..............
NINDS...................................           1,170  ..............
NIAID...................................             540  ..............
NIGMS...................................           1,350  ..............
NICHD...................................             900  ..............
NEI.....................................             360  ..............
NIEHS...................................             900  ..............
NIA.....................................             630  ..............
NIAMS...................................             360  ..............
NIDCD...................................             360  ..............
NIMH....................................             900  ..............
NIDA....................................             540  ..............
NIAAA...................................             270  ..............
NINR....................................             180  ..............
NHGRI...................................             270  ..............
NIBIB...................................             450  ..............
NCRR....................................              90          10,000
NCCAM...................................             180  ..............
NCMHD...................................             270  ..............
FIC.....................................             180  ..............
NLM.....................................             450  ..............
                                         -------------------------------
      Total.............................          15,750          10,000
------------------------------------------------------------------------
CTSA = Clinical Translational Science Awards


                                                                  APPROPRIATION HISTORY
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                         Budget request to
                     Fiscal year                              Congress             House allowance          Senate allowance        Appropriation \1\
--------------------------------------------------------------------------------------------------------------------------------------------------------
1999................................................      \2\ $14,763,313,000          $14,862,023,000          $15,622,386,000      \3\ $15,629,156,000
2000................................................       \4\ 15,932,786,000           16,964,547,000           17,613,470,000       \5\ 17,820,587,000
2001................................................       \6\ 18,812,735,000           20,512,735,000           20,512,735,000   \7\ \8\ 20,458,130,000
 2002...............................................           23,112,130,000           22,945,199,000           23,765,488,000            \9\ \10\ \11\
                                                                                                                                          23,296,382,000
 2003...............................................      \12\ 27,343,417,000           27,351,717,000           27,369,000,000      \13\ 27,066,782,000
 2004...............................................           27,892,765,000           28,043,991,000           28,369,548,000      \14\ 27,887,512,000
 2005...............................................           28,757,357,000           28,657,357,000           28,901,185,000      \15\ 28,495,157,000
 2006...............................................           28,740,073,000           28,737,094,000           29,644,804,000      \16\ 28,461,417,000
 2007...............................................           28,578,417,000      \17\ 28,479,417,000      \17\ 28,779,081,000      \18\ 29,228,004,000
 2008...............................................           28,849,675,000  .......................  .......................  .......................
--------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Reflects enacted supplementals, rescissions and reappropriations.
\2\ Reflects a decrease of $34,530,000 for the budget amendment for bioterrorism. Includes $1,728,099,000 for HIV research in the NIH Office of AIDS
  Research.
\3\ Includes $1,800,046,000 appropriated to the ICs for HIV research. Includes $10,230,000 for rescission.
\4\ Includes $1,833,826,000 for HIV research in the NIH Office of AIDS Research. Includes $40 million appropriated in fiscal year 1999 for the Clinical
  Research Center.
\5\ Includes $2,024,956,000 appropriated to the ICs for HIV research. Includes $99,883,000 for NIH share of across-the-board reduction and reflects
  $20,000,000 transferred to CDC. Includes $40,000,000 in forward funding appropriated in fiscal year 1999.
\6\ Includes $2,111,224,000 for HIV research in the NIH Office of AIDS Research.
\7\ Includes $2,244,987,000 appropriated to the ICs for HIV research. Reflects NIH share of across-the-board reduction ($8,666,000) and $5,800,000
  transferred to the DHHS.
\8\ In fiscal year 2001, NIH began receiving a separate appropriation for Superfund Research activities at NIEHS.
\9\ Includes $2,535,672,000 appropriated to the ICs for HIV research. Reflects NIH share of across-the-board reduction ($9,273,000), Labor/HHS
  ($22,946,000) and government-wide ($34,243,000) rescissions, and transfer of $100M to the Global Fund for HIV/AIDS, malaria, and tuberculosis.
\10\ Includes $10.5 million appropriated from the Emergency Relief Fund.
\11\ Beginning with the fiscal year 2002 Appropriation, includes amounts authorized to the NIDDK for Type 1 diabetes research.
\12\ Excludes $583,000 transferred to the Department of Homeland Security.
\13\ Includes $2,747,463,000 appropriated to the ICs for HIV research. Reflects NIH share of the across-the-board reduction ($177,085,000), and
  transfers of $99,350,000 to the Global Fund for HIV/AIDS, malaria, and tuberculosis, and $583,000 to the Department of Homeland Security.
\14\ Includes $2,850,581,000 appropriated to the ICs for HIV research. Reflects NIH share of across-the-board reduction ($165,459,000), Labor/HHS
  rescission ($17,492,000), and transfer of $149,115,000 to the Global Fund for HIV/AIDS, malaria, and tuberculosis.
\15\ Includes $2,920,551,000 appropriated to the ICs for HIV research. Reflects NIH share of across-the-board reduction ($229,390,000), Labor/HHS
  rescission ($6,787,000), and transfer of $99,200,000 to the Global Fund for HIV/AIDS, malaria, and tuberculosis.
\16\ Includes $2,903,664,000 appropriated to the ICs for HIV research. Reflects NIH share of the Government-wide rescission ($287,356,000), and transfer
  of $99,000,000 to the Global Fund for HIV/AIDS, malaria, and tuberculosis.
\17\ Reflects funding levels approved by the Appropriations Committees. Neither chamber had passed the Labor/HHS appropriations bill at the time this
  budget was prepared.
\18\ Joint Resolution.


                                                                                     HISTORY OF CONGRESSIONAL APPROPRIATIONS, FISCAL YEARS 1998-2007
                                                                                                        [In thousands of dollars]
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                           Fiscal year                                NCI        NHLBI       NIDCR       NIDDK       NINDS       NIAID       NIGMS       NICHD        NEI        NIEHS        NIA        NIAMS       NIDCD       NIMH
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
1998............................................................   2,547,314   1,531,061     209,415     900,860     780,713   1,351,655   1,065,947     674,766     355,691     330,108     519,279     274,760     200,695     750,241
1999............................................................   2,925,247   1,792,509     234,183   1,020,559     902,680   1,569,063   1,197,026     750,485     395,595     375,494     596,126     307,960     229,735     860,638
2000............................................................   3,314,554   2,029,424     268,811   1,168,476   1,029,376   1,778,038   1,354,420     858,291     450,300     442,449     686,479     349,968     263,771     973,146
2001............................................................   3,754,456   2,298,512     306,211   1,399,684   1,175,854   2,041,698   1,535,378     975,766     510,352     564,810     785,590     396,460     300,418   1,106,305
2002............................................................   4,181,233   2,572,667     342,664   1,562,144   1,326,666   2,342,313   1,724,799   1,111,674     580,713     645,422     892,267     448,248     341,675   1,246,640
2003............................................................   4,592,348   2,793,733     371,636   1,722,730   1,456,476   3,606,789   1,847,000   1,205,927     633,148     697,767     993,598     486,143     370,382   1,341,014
2004............................................................   4,739,255   2,878,691     383,282   1,821,803   1,501,207   4,155,447   1,904,838   1,242,361     653,052     710,701   1,024,754     501,066     382,053   1,381,774
2005............................................................   4,825,258   2,941,201     391,829   1,863,584   1,539,448   4,303,641   1,944,067   1,270,321     669,070     724,347   1,051,990     511,157     394,260   1,411,933
2006............................................................   4,793,356   2,921,757     389,336   1,854,925   1,534,757   4,315,801   1,935,618   1,264,769     666,756     720,240   1,046,631     507,932     393,458   1,403,515
2007............................................................   4,797,639   2,922,929     389,703   1,855,868   1,535,545   4,417,208   1,935,808   1,254,707     667,116     721,119   1,047,260     508,240     393,668   1,404,494
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------


----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                          Fiscal year                              NIDA        NIAAA       NINR        NHGRI       NIBIB       NCRR        NCCAM       NCMHD        FIC         NLM         OD          B&F         OAR         TOTAL
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
1998..........................................................     527,175     227,175      63,597     217,704  ..........     453,883  ..........  ..........      28,289     161,185     296,373     206,957  ..........  \1\ 13,674,8
                                                                                                                                                                                                                                      43
1999..........................................................     602,874     259,575      69,788     264,707  ..........     554,446  ..........  ..........      35,402     181,189     306,356     197,519  ..........  \2\ 15,629,1
                                                                                                                                                                                                                                      56
2000..........................................................     685,781     292,369      89,522     335,527  ..........     676,557      68,390  ..........      43,494     214,068     282,000     165,376  ..........  \3\ 17,820,5
                                                                                                                                                                                                                                      87
2001..........................................................     780,833     340,453     104,328     382,112  ..........     817,253      89,138     130,096      50,482     246,351     211,800     153,790  ..........  \4\ 20,458,1
                                                                                                                                                                                                                                      30
2002..........................................................     886,718     383,615     120,366     428,758     111,861   1,011,262     104,451     157,563      56,859     276,091     235,113     204,600  ..........  \5\ 23,296,3
                                                                                                                                                                                                                                      82
2003..........................................................     961,721     416,051     130,584     464,995     278,279   1,138,821     113,407     185,714     163,465     300,135     266,232     628,687  ..........  \6\ 27,066,7
                                                                                                                                                                                                                                      82
2004..........................................................     990,953     428,669     134,724     479,073     287,129   1,179,058     116,978     191,471      65,382     317,315     327,504      88,972  ..........  \7\ 27,887,5
                                                                                                                                                                                                                                      12
2005..........................................................   1,006,419     438,277     138,072     488,608     298,209   1,115,090     122,105     196,159      66,632     315,146     358,046     110,288  ..........  \8\ 28,495,1
                                                                                                                                                                                                                                      57
2006..........................................................   1,000,029     435,930     137,342     486,049     296,810   1,099,101     121,465     195,405      66,378     314,910     478,066      81,081  ..........  \9\ 28,461,4
                                                                                                                                                                                                                                      17
2007..........................................................   1,000,621     436,259     137,404     486,491     296,887   1,133,240     121,576     199,444      66,446     320,850   1,096,401      81,081  ..........  \10\ 29,228,
                                                                                                                                                                                                                                     004
----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Funds for HIV research in the amount of $1,607,053,000 appropriated to the ICs. Beginning in fiscal year 1998, includes funds appropriated to NIDDK for Type 1 diabetes research.
\2\ Funds for HIV research in the amount of $1,800,046,000 appropriated to the ICs. Reflects rescission of $10,230,000.
\3\ Funds for HIV research in the amount of $2,024,956 appropriated to the ICs. Reflects NIH share of across-the-board reduction ($99,883,000) and transfer to CDC ($20,000,000). Includes $40,000,000 in forward funding appropriated
  in fiscal year 1999.
\4\ Funds for HIV research in the amount of $2,244,987,000 appropriated to the ICs. Reflects NIH share of across-the-board reduction ($8,666,000) and transfer to DHHS ($5,800,000). In fiscal year 2001, NIH began receiving a separate
  appropriation for Superfund Research activities at NIEHS.
\5\ Funds for HIV research in the amount of $2,535,672,000 appropriated to the ICs. Reflects NIH share of across-the-board reduction ($9,273,000), Labor/HHS ($22,946,000) and government-wide ($34,243,000) rescissions, and transfer
  of $100M to the Global Fund for HIV/AIDS, malaria, and tuberculosis.
\6\ Funds for HIV research in the amount of $2,747,463,000 appropriated to the ICs. Reflects NIH share of across-the-board reduction ($177,085,000), and transfers of $99,350,000 to the Global Fund for HIV/AIDS, malaria, and
  tuberculosis, and $583,000 to the Department of Homeland Security.
\7\ Funds for HIV research in the amount of $2,850,581,000 appropriated to the ICs. Reflects NIH share of across-the-board reduction ($165,459,000), Labor/HHS rescission ($17,492,000), and transfer of $149,115,000 to the Global Fund
  for HIV/AIDS, malaria, and tuberculosis.
\8\ Funds for HIV research in the amount of $2,920,551,000 appropriated to the ICs. Reflects NIH share of across-the-board reduction ($229,390,000), Labor/HHS rescission ($6,787,000), and transfer of $99,200,000 to the Global Fund
  for HIV/AIDS, malaria, and tuberculosis.
\9\ Funds for HIV research in the amount of $2,903,664,000 appropriated to the ICs. Reflects NIH share of the Government-wide rescission ($287,356,000), and transfer of $99,000,000 to the Global Fund for HIV/AIDS, malaria, and
  tuberculosis.
\10\ Joint Resolution.


                          FULL-TIME EQUIVALENTS
------------------------------------------------------------------------
                                                Fiscal year
                                  --------------------------------------
      Institutes and Centers                                     2008
                                   2006 actual   2007 Joint  President's
                                                 resolution     budget
------------------------------------------------------------------------
NCI..............................        2,777        2,835        2,875
NHLBI............................          797          806          817
NIDCR............................          245          252          256
NIDDK............................          638          646          655
NINDS............................          526          539          547
NIAID............................        1,589        1,617        1,639
NIGMS............................          125          126          129
NICHD............................          547          548          557
NEI..............................          207          213          215
NIEHS............................          664          668          677
NIA..............................          378          381          386
NIAMS............................          211          214          217
NIDCD............................          133          136          138
NIMH.............................          616          641          651
NIDA.............................          361          366          371
NIAAA............................          225          227          230
NINR.............................           43           44           45
NHGRI............................          292          301          305
NIBIB............................           48           50           51
NCRR.............................           99          108          109
NCCAM............................           74           76           77
NCMHD............................           25           29           31
FIC..............................           52           54           55
                                  --------------------------------------
      Subtotals, ICs.............       10,672       10,877       11,033
NLM..............................          656          662          671
OD...............................          578          630          638
Central Services.................        4,966        5,037        5,107
                                  --------------------------------------
      Subtotal, NIH..............       16,872       17,206       17,449
Undistributed....................  ...........  ...........  ...........
Ceiling exempt \1\...............            8           10           10
                                  --------------------------------------
      Total, NIH.................       16,880       17,216       17,459

------------------------------------------------------------------------
\1\ CRADA FTEs are supported by Cooperative Research and Development
  Agreements


                                         BUDGET AUTHORITY BY OBJECT \1\
----------------------------------------------------------------------------------------------------------------
                                                                     Fiscal year
                                                       --------------------------------------     Increase or
                           Object Classes                   2007 Joint                             decrease
                                                            Resolution       2008 estimate
----------------------------------------------------------------------------------------------------------------
      Personnel Compensation:
    11.1  Full-Time Permanent                              $838,033,000       $881,383,000        $43,350,000
    11.3  Other than Full-Time Permanent                    263,580,000        276,142,000         12,562,000
    11.5  Other Personnel Compensation                       29,783,000         31,112,000          1,329,000
    11.7  Military Personnel                                 26,032,000         27,721,000          1,689,000
    11.8  Special Personnel Services Payments               171,584,000        175,795,000          4,211,000
                                                     -----------------------------------------------------------
            Total, Personnel Compensation                 1,329,012,000      1,392,153,000         63,141,000
                                                     ===========================================================
    12.1  Civilian Personnel Benefits                       311,004,000        326,309,000         15,305,000
    12.2  Military Personnel Benefits                        17,255,000         18,026,000            771,000
    13.0  Benefits for Former Personnel               .................  .................  ..................
                                                     -----------------------------------------------------------
            Subtotal, Pay Costs                           1,657,271,000      1,736,488,000         79,217,000
                                                     ===========================================================
    21.0  Travel & Transportation of Persons                 55,429,000         52,639,000         (2,790,000)
    22.0  Transportation of Things                            5,174,000          4,938,000           (236,000)
    23.1  Rental Payments to GSA                                 64,000             61,000             (3,000)
    23.2  Rental Payments to Others                           1,380,000          1,373,000             (7,000)
    23.3  Communications, Utilities & Miscellaneous          29,949,000         29,770,000           (179,000)
           Charges
    24.0  Printing & Reproduction                            14,418,000         14,093,000           (325,000)
    25.1  Consulting Services                               120,471,000        117,621,000         (2,850,000)
    25.2  Other Services                                    515,643,000        485,772,000        (29,871,000)
    25.3  Purchase of Goods & Services from               2,526,800,000      2,508,161,000        (18,639,000)
           Government Accounts
    25.4  Operation & Maintenance of Facilities             297,892,000        263,545,000        (34,347,000)
    25.5  Research & Development Contracts                2,140,434,000      2,315,525,000        175,091,000
    25.6  Medical Care                                       16,482,000         16,110,000           (372,000)
    25.7  Operation & Maintenance of Equipment               76,450,000         72,506,000         (3,944,000)
    25.8  Subsistence & Support of Persons            .................  .................  ..................
                                                     -----------------------------------------------------------
    25.0    Subtotal, Other Contractual Services          5,694,172,000      5,779,240,000         85,068,000
                                                     ===========================================================
    26.0  Supplies & Materials                              216,416,000        201,809,000        (14,607,000)
    31.0  Equipment                                         126,456,000        119,236,000         (7,220,000)
    32.0  Land and Structures                         .................  .................  ..................
    33.0  Investments & Loans                         .................  .................  ..................
    41.0  Grants, Subsidies & Contributions              21,297,989,000     20,831,478,000       (466,511,000)
    42.0  Insurance Claims & Indemnities                         10,000             10,000  ..................
    43.0  Interest & Dividends                                  117,000            106,000            (11,000)
    44.0  Refunds                                     .................  .................  ..................
                                                     -----------------------------------------------------------
            Subtotal, Non-Pay Costs                      27,441,574,000     27,034,753,000       (406,821,000)
                                                     -----------------------------------------------------------
            Total Budget Authority by Object             29,098,845,000     28,771,241,000       (327,604,000)

----------------------------------------------------------------------------------------------------------------
      \1\ Reflects request to Labor/HHS/Education Subcommittee, and includes Type 1 Diabetes funds provided
        through Public Law 107-360.


              BUDGET AUTHORITY BY OBJECT INCLUDING SERVICE AND SUPPLY FUND AND MANAGEMENT FUND \1\
----------------------------------------------------------------------------------------------------------------
                                                                     Fiscal year
                                                       --------------------------------------     Increase or
                           Object Classes                   2007 Joint                             Decrease
                                                            Resolution       2008 Estimate
----------------------------------------------------------------------------------------------------------------
      Personnel Compensation:
    11.1  Full-Time Permanent                            $1,115,616,000     $1,168,343,000        $52,727,000
    11.3  Other than Full-Time Permanent                    339,113,000        353,676,000         14,563,000
    11.5  Other Personnel Compensation                       48,648,000         50,402,000          1,754,000
    11.7  Military Personnel                                 35,988,000         37,905,000          1,917,000
    11.8  Special Personnel Services Payments               175,535,000        179,832,000          4,297,000
                                                     -----------------------------------------------------------
      Total, Personnel Compensation                       1,714,900,000      1,790,158,000         75,258,000
    12.1  Civilian Personnel Benefits                       416,629,000        434,651,000         18,022,000
    12.2  Military Personnel Benefits                        21,800,000         22,647,000            847,000
    13.0  Benefits for Former Personnel                         661,000            672,000             11,000
                                                     -----------------------------------------------------------
            Subtotal, Pay Costs                           2,153,990,000      2,248,128,000         94,138,000
    21.0  Travel & Transportation of Persons                 58,562,000         56,236,000         (2,326,000)
    22.0  Transportation of Things                            6,602,000          6,369,000           (233,000)
    23.1  Rental Payments to GSA                             40,154,000         40,402,000            248,000
    23.2  Rental Payments to Others                          85,139,000         85,657,000            518,000
    23.3  Communications, Utilities & Miscellaneous         148,541,000        149,124,000            583,000
           Charges
    24.0  Printing & Reproduction                            21,749,000         21,448,000           (301,000)
    25.1  Consulting Services                               136,456,000        133,654,000         (2,802,000)
    25.2  Other Services                                  1,002,883,000        974,048,000        (28,835,000)
    25.3  Purchase of Goods & Services from                 858,478,000        821,161,000        (37,317,000)
           Government Accounts
    25.4  Operation & Maintenance of Facilities             415,313,000        381,429,000        (33,884,000)
    25.5  Research & Development Contracts                2,143,108,000      2,318,213,000        175,105,000
    25.6  Medical Care                                       24,463,000         23,703,000           (760,000)
    25.7  Operation & Maintenance of Equipment              173,642,000        170,147,000         (3,495,000)
    25.8  Subsistence & Support of Persons            .................  .................  ..................
                                                     -----------------------------------------------------------
    25.0    Subtotal, Other Contractual Services          4,754,343,000      4,822,355,000         68,012,000
    26.0  Supplies & Materials                              336,691,000        321,810,000        (14,881,000)
    31.0  Equipment                                         194,842,000        188,002,000         (6,840,000)
    32.0  Land and Structures                                    77,000             77,000  ..................
    33.0  Investments & Loans                         .................  .................  ..................
    41.0  Grants, Subsidies & Contributions              21,297,989,000     20,831,478,000       (466,511,000)
    42.0  Insurance Claims & Indemnities                         14,000             14,000  ..................
    43.0  Interest & Dividends                                  152,000            141,000            (11,000)
    44.0  Refunds                                     .................  .................  ..................
                                                     -----------------------------------------------------------
            Subtotal, Non-Pay Costs                      26,944,855,000     26,523,113,000       (421,742,000)
                                                     -----------------------------------------------------------
            Total Budget Authority by Object             29,098,845,000     28,771,241,000       (327,604,000)
----------------------------------------------------------------------------------------------------------------
      \1\ Reflects request to Labor/HHS/Education Subcommittee, and includes Type I Diabetes funds provided
        through Public Law 107-360


                                              SALARIES AND EXPENSES
----------------------------------------------------------------------------------------------------------------
                                                                     Fiscal year
                                                       --------------------------------------     Increase or
                    Object Classes                          2007 Joint                             decrease
                                                            resolution       2008 estimate
----------------------------------------------------------------------------------------------------------------
Personnel Compensation:...............................
    Full-Time Permanent (11.1)........................       $838,033,000       $881,383,000        $43,350,000
    Other Than Full-Time Permanent (11.3).............        263,580,000        276,142,000         12,562,000
    Other Personnel Compensation (11.5)...............         29,783,000         31,112,000          1,329,000
    Military Personnel (11.7).........................         26,032,000         27,721,000          1,689,000
    Special Personnel Services Payments (11.8)........        171,584,000        175,795,000          4,211,000
                                                       ---------------------------------------------------------
      Total Personnel Compensation (11.9).............      1,329,012,000      1,392,153,000         63,141,000
Civilian Personnel Benefits (12.1)....................        311,004,000        326,309,000         15,305,000
Military Personnel Benefits (12.2)....................         17,255,000         18,026,000            771,000
Benefits to Former Personnel (13.0)...................  .................  .................  ..................
                                                       ---------------------------------------------------------
      Subtotal, Pay Costs.............................      1,657,271,000      1,736,488,000         79,217,000
Travel (21.0).........................................         55,429,000         52,639,000         (2,790,000)
Transportation of Things (22.0).......................          5,174,000          4,938,000           (236,000)
Rental Payments to Others (23.2)......................          1,380,000          1,373,000             (7,000)
Communications, Utilities and Miscellaneous Charges            29,949,000         29,770,000           (179,000)
 (23.3)...............................................
Printing and Reproduction (24.0)......................         14,418,000         14,093,000           (325,000)
Other Contractual Services:
    Advisory and Assistance Services (25.1)...........        103,157,000        100,069,000         (3,088,000)
    Other Services (25.2).............................        515,643,000        485,772,000        (29,871,000)
    Purchases from Govt. Accounts (25.3)..............      1,177,590,000      1,146,018,000        (31,572,000)
    Operation & Maintenance of Facilities (25.4)......         62,671,000         62,582,000            (89,000)
    Operation & Maintenance of Equipment (25.7).......         76,450,000         72,506,000         (3,944,000)
    Subsistence & Support of Persons (25.8)...........  .................  .................  ..................
                                                       ---------------------------------------------------------
      Subtotal Other Contractual Services.............      1,935,511,000      1,866,947,000        (68,564,000)
Supplies and Materials (26.0).........................        216,416,000        201,809,000        (14,607,000)
                                                       ---------------------------------------------------------
      Subtotal, Non-Pay Costs.........................      2,258,277,000      2,171,569,000        (86,708,000)
                                                       ---------------------------------------------------------
      Total, Administrative Costs.....................      3,915,548,000      3,908,057,000         (7,491,000)
----------------------------------------------------------------------------------------------------------------


                                SALARIES AND EXPENSES--TOTAL--MODIFIED DEFINITION
----------------------------------------------------------------------------------------------------------------
                                                                            Fiscal year
                                                                 --------------------------------
                     Institutes and centers                                            2008       Percent change
                                                                    2007 Joint      President's
                                                                    resolution        budget
----------------------------------------------------------------------------------------------------------------
NCI.............................................................    $312,200,000    $315,226,000             1.0
NHLBI...........................................................     107,364,000     108,390,000             1.0
NIDCR...........................................................      20,949,000      21,151,000             1.0
NIDDK...........................................................      60,867,000      61,450,000             1.0
NINDS...........................................................      54,003,000      54,561,000             1.0
NIAID...........................................................     229,065,000     231,142,000             0.9
NIGMS...........................................................      47,317,000      48,300,000             2.1
NICHD...........................................................      57,594,000      58,425,000             1.4
NEI.............................................................      22,905,000      23,098,000              .8
NIEHS...........................................................      22,141,000      22,313,000              .8
NIA.............................................................      37,554,000      37,942,000             1.0
NIAMS...........................................................      23,537,000      23,737,000              .8
NIDCD...........................................................      18,434,000      18,624,000             1.0
NIMH............................................................      73,171,000      73,901,000             1.0
NIDA............................................................      57,628,000      58,205,000             1.0
NIAAA...........................................................      26,946,000      27,179,000              .9
NINR............................................................       9,367,000       9,464,000             1.0
NHGRI...........................................................      18,412,000      18,581,000              .9
NCRR............................................................      27,957,000      28,235,000             1.0
NCCAM...........................................................      12,698,000      12,824,000             1.0
NCMHD...........................................................      10,154,000      10,260,000             1.0
NIBIB...........................................................      17,155,000      17,353,000             1.2
FIC.............................................................      12,582,000      12,708,000             1.0
NLM.............................................................       9,875,000       9,855,000            -0.2
OD..............................................................     114,136,000     107,471,000            -5.8
Clinical Center.................................................      18,248,000      18,431,000             1.0
                                                                 -----------------------------------------------
      Total.....................................................   1,422,259,000   1,428,826,000             0.5
Public Health Education Excluded from above.....................    (28,384,000)    (28,779,000)             1.4

----------------------------------------------------------------------------------------------------------------
Note.--Section 408 of the PHS Act, as amended, defines administrative expenses as expenses incurred for the
  support of activities relevant to the award of grants, contracts, and cooperative agreements and expenses
  incurred for general administration of the scientific programs and activities of the National Institutes of
  Health.
In collaboration with staff of the General Accounting Office (GAO), a methodology was developed to account for
  administrative expenses as defined in Section 408. This methodology includes obligations in the RMS budget
  activity (except for Program Evaluation costs), obligations directly related to the administrative
  responsibilities of the Office of the Scientific Director in the Intramural budget activity, and
  administrative expenses in the Cancer Control program.
In addition, direct program costs in the Office of the Director (those for the Director's Discretionary Fund,
  AIDS research, the Office of Women's Health Research, the Office of Education, the Office of Behavioral and
  Social Science Research, the Office of Dietary Supplements, the Loan Repayment Programs, and the Office of
  Rare Diseases Research) have been excluded.
The definition of administrative expenses has been further modified to include those activities specifically
  excluded by the law (NINR, FIC, NLM, and the Clinical Center), and to exclude public health education
  activities. This is consistent with previous House Appropriations subcommittee requests on administrative
  costs using this definition.
Major cost categories excluded from this definition but included in the OMB/HHS definition of administrative
  costs: salaries and benefits for researchers; travel for patients undergoing treatment at the Clinical Center
  and travel to scientific workshops and conferences; costs associated with laboratory facilities; contractual
  support for R&D activities in the Intramural program; and scientific supplies.


                                               STATISTICAL DATA--GRANTS, DIRECT AND INDIRECT COSTS AWARDED
                                                                  [Dollars in millions]
--------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                         Percent to total in        Percent growth in
                                                                  Direct      Indirect      Total              dollars                   dollars
                         Fiscal year                              costs        costs       dollars   ---------------------------------------------------
                                                                 awarded      awarded      awarded       Direct      Indirect      Direct      Indirect
--------------------------------------------------------------------------------------------------------------------------------------------------------
1996.........................................................       $6,214       $2,627       $8,840         70.3         29.7  ...........  ...........
1998.........................................................        7,246        3,038       10,284         70.5         29.5  ...........  ...........
1999.........................................................        8,391        3,421       11,811         71.0         29.0         15.8         12.6
2000.........................................................        9,787        3,881       13,668         71.6         28.4         16.6         13.5
2001.........................................................       11,210        4,425       15,634         71.7         28.3         14.5         14.0
2002.........................................................       12,721        4,937       17,658         72.0         28.0         13.5         11.6
2003.........................................................       14,337        5,410       19,747         72.6         27.4         12.7          9.6
2004.........................................................       14,780        5,760       20,540         72.0         28.0          3.1          6.5
2005.........................................................       15,299        5,915       21,214         72.1         27.9          3.5          2.7
2006.........................................................       15,095        5,905       21,000         71.9         28.1         -1.3         -0.2
2007 Joint Resolution........................................       15,290        5,982       21,272         71.9         28.1          1.3          1.3
2008 President's Budget......................................       15,049        5,887       20,936         71.9         28.1         -1.6         -1.6

--------------------------------------------------------------------------------------------------------------------------------------------------------
Note.--Fiscal year 2007-2008 data is preliminary, and will change as actual data is received.


                                                                   RESEARCH PROJECT GRANTS--TOTAL NUMBER OF AWARDS AND DOLLARS
                                                                                     [Dollars in thousands]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                Fiscal year
                                         -------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                                                         2008
                                                                                                                                                                            2007       revised
                                             1995       1996       1997       1998       1999       2000       2001      2002      2003      2004      2005      2006       joint    President's
                                                                                                                                                                         resolution     budget
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
No. of Awards:
    Competing...........................      6,759      6,653      7,390      7,578      8,566      8,765      9,101     9,396    10,411    10,020     9,599     9,129     10,154        9,404
    Noncompeting........................     17,069     17,854     18,248     19,495     20,149     21,779     23,322    24,921    25,776    27,040    27,385    27,366     26,668       26,573
                                         -------------------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal (includes Non-  comp)....     23,828     24,507     25,638     27,073     28,715     30,544     32,423    34,317    36,187    37,060    36,984    36,495     36,822       35,977
SBIR....................................      1,071      1,012      1,298      1,326      1,508      1,640      1,699     1,889     2,032     2,181     1,924     1,822      1,463        1,543
                                         -------------------------------------------------------------------------------------------------------------------------------------------------------
      Total.............................     24,899     25,519     26,936     28,399     30,223     32,184     34,122    36,206    38,219    39,241    38,908    38,317     38,285       37,520
                                         =======================================================================================================================================================
Average Annual Cost:
    Competing...........................     $231.2     $244.6     $245.9     $255.9     $293.6     $332.2     $333.1    $338.8    $337.8    $355.7    $354.8    $368.3     $367.5       $350.3
                                         -------------------------------------------------------------------------------------------------------------------------------------------------------
      Total (includes noncomp)..........     $252.7     $262.1     $269.3     $277.7     $294.8     $319.4     $344.7    $365.5     $79.9    $392.9    $401.8    $403.2     $402.1       $402.3
                                         =======================================================================================================================================================
Percent Change over prior year average
 costs:
    Competing RPGs......................        2.8        5.8        0.5        4.0       14.7       13.2        0.3       1.7      -0.3       5.3      -0.2       3.8       -0.2         -4.7
                                         -------------------------------------------------------------------------------------------------------------------------------------------------------
      Total RPGs........................        3.8        3.7        2.7        3.1        6.2        8.4        7.9       6.0       3.9       3.4       2.3       0.4       -0.3   ...........
Average Length of Award in Years........        3.8        3.8        3.8        3.8        3.9        3.9        3.9       3.9       3.8       3.7       3.7       3.8        3.7          3.8
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ As a policy, no inflationary increases were provided for competing RPGs. The apparent decrease in average cost in fiscal year 2008 is the result of an extremely large cohort of AIDS
  clinical trials cycling from competing into noncompeting status. (77 awards, average cost $1.8 million per award). While there will be no inflationary increases for direct, recurring costs
  in Noncompeting continuation RPGs, where the NIH has committed to a programmatic increase in an award, such increases will be provded.
Numbers of grants identified in fiscal year 2007 and fiscal year 2008 are estimates, and WILL change as applications are received and selected for funding.


                                                                         RESEARCH PROJECT GRANTS--FISCAL YEARS 1999-2008
                                                                                   [Percent of success Rates]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                           Fiscal year
                                                               ---------------------------------------------------------------------------------------------------------------------------------
                    Institutes and centers                                                                                                                                               2008
                                                                    1999         2000         2001         2002         2003         2004         2005         2006      2007 joint  President's
                                                                                                                                                                         resolution     budget
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
NCI...........................................................           32           26           27           28           27           24           20           19           19           17
NHLBI.........................................................           36           35           36           33           34           29           24           20           19           18
NIDCR.........................................................           24           27           34           29           27           30           24           19           20           15
NIDDK.........................................................           33           28           29           34           33           27           24           21           19           17
NINDS.........................................................           35           37           32           29           30           25           22           18           19           18
NIAID.........................................................           34           36           38           36           35           24           25           21           22           21
NIGMS.........................................................           39           37           37           39           38           30           27           26           31           25
NICHD.........................................................           30           29           27           28           27           17           18           15           19           15
NEI...........................................................           40           42           40           41           33           30           26           23           23           23
NIEHS.........................................................           27           29           29           29           25           19           19           22           19           11
NIA...........................................................           28           26           32           28           29           21           19           17           19           17
NIAMS.........................................................           24           27           29           23           20           20           20           19           17           17
NIDCD.........................................................           34           40           42           39           38           35           27           28           29           25
NIMH..........................................................           27           29           31           28           27           24           21           20           22           19
NIDA..........................................................           34           38           36           31           35           27           22           20           19           18
NIAAA.........................................................           30           31           33           32           27           29           31           27           31           30
NINR..........................................................           14           32           26           26           27           21           24           18           21           17
NHGRI.........................................................           38           43           42           15           30           23           18           34           38           32
NIBIB.........................................................          N/A          N/A          N/A          N/A           19           17           20           17           18           16
NCRR..........................................................           34           18           29           30           28           21           14           13           21           17
NCCAM.........................................................           57           29           17           14           14           17           17           14           17           21
NCMHD \1\.....................................................          N/A          N/A          N/A          N/A          N/A          N/A          N/A          N/A          N/A          N/A
FIC...........................................................           39           23           30           28           19           22           24           19           20           18
ROADMAP.......................................................          N/A          N/A          N/A          N/A          N/A           13           17           10           18           10
                                                               ---------------------------------------------------------------------------------------------------------------------------------
      NIH.....................................................           32           32           32           31           30           25           22           20           21          18
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ NCMHD success rate is N/A due to co-funding agreements with other IC's.

Note.--Success rates identified in fiscal year 2007 and fiscal year 2008 are estimates, and WILL change as applications are received and selected for funding.


                                                            HISTORY OF OBLIGATIONS BY INSTITUTE OR CENTER \1\--FISCAL YEARS 1999-2008
                                                                                    [In thousands of dollars]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                    Fiscal year
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                                            2007         2008
              Institutes and centers                                                                                                                           2006       revised      revised
                                                       1999         2000         2001         2002         2003         2004         2005     2006 actual    comp.\1\      joint     President's
                                                                                                                                                                         resolution     budget
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
NCI..............................................    2,918,050    3,314,580    3,758,566    4,177,830    4,595,477    4,727,365    4,797,731    4,754,121    4,795,073    4,795,491    4,782,114
NHLBI............................................    1,788,008    2,027,286    2,298,035    2,569,794    2,793,681    2,882,601    2,922,573    2,893,527    2,915,923    2,919,980    2,925,413
NIDCR............................................      233,605      268,521      306,152      342,292      371,630      382,013      389,346      385,589      388,664      389,370      389,722
NIDDK............................................    1,018,063    1,167,110    1,399,184    1,560,013    1,712,959    1,829,473    1,852,592    1,838,511    1,853,149    1,855,226    1,858,045
NINDS............................................      900,245    1,028,204    1,175,591    1,325,193    1,456,426    1,498,203    1,529,654    1,519,971    1,533,045    1,534,904    1,537,019
NIAID............................................    1,565,201    1,777,154    2,041,311    2,339,779    3,606,789    4,141,769    4,276,433    4,274,201    4,379,199    4,366,445    4,592,482
NIGMS............................................    1,203,079    1,366,994    1,535,056    1,722,890    1,846,917    1,915,130    1,931,690    1,916,927    1,934,043    1,935,625    1,941,462
NICHD............................................      748,626      857,354      975,537    1,110,459    1,205,908    1,247,939    1,262,273    1,252,598    1,263,521    1,254,144    1,264,946
NEI..............................................      394,601      449,759      510,241      580,047      633,109      650,961      664,840      660,340      665,768      666,675      667,820
NIEHS............................................      374,527      441,960      501,813      574,518      614,183      630,254      640,405      630,447      635,995      641,773      637,406
NIA..............................................      594,556      685,695      785,413      891,282      993,595    1,021,376    1,045,339    1,036,559    1,045,201    1,046,500    1,047,148
NIAMS............................................      307,160      349,555      396,305      447,682      486,031      499,368      507,843      502,954      507,416      508,060      508,082
NIDCD............................................      229,162      263,448      300,282      341,260      370,330      380,737      391,679      389,623      393,111      393,540      393,682
NIMH.............................................      858,520      972,127    1,106,095    1,245,292    1,341,014    1,379,225    1,403,007    1,390,009    1,401,813    1,403,570    1,405,421
NIDA.............................................      611,061      694,561      790,185      892,639      965,721      991,510    1,000,056      990,405      998,858    1,000,014    1,000,365
NIAAA............................................      258,874      291,928      340,151      383,174      415,960      427,223      435,503      431,726      435,479      436,057      436,505
NINR.............................................       69,600       89,415      104,294      120,217      130,537      134,279      137,199      136,020      137,150      137,287      137,800
NHGRI............................................      279,030      335,129      381,971      428,248      464,960      490,546      485,500      481,339      485,655      486,427      484,436
NIBIB............................................  ...........  ...........  ...........      111,740      278,279      286,684      296,324      293,954      298,088      298,391      300,463
NCRR.............................................      562,082      676,077      817,098    1,010,169    1,138,820    1,191,556    1,108,028    1,088,500    1,108,947    1,143,841    1,112,498
NCCAM............................................       40,464       77,808       89,120      104,334      113,405      116,590      121,333      120,294      121,134      121,379      121,699
NCMHD............................................  ...........  ...........      130,070      157,364      185,674      190,824      194,904      193,522      195,263      199,429      194,495
FIC..............................................       35,307       43,446       50,430       56,787       63,425       65,160       66,164       65,726       66,317       66,422       66,594
NLM..............................................      181,014      213,730      239,068      275,395      299,771      310,165      312,980      311,721      314,078      320,229      312,562
OD...............................................      255,584      281,587      212,482      234,784      266,161      327,267      533,673      724,831      478,307    1,096,985      517,062
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal...................................   15,426,419   17,673,428   20,244,450   23,003,182   26,350,762   27,718,218   28,307,069   28,283,415   28,351,197   29,017,764   28,635,241
B&F..............................................      216,856      140,311      205,756      114,839      305,628      303,254      239,246      170,456       85,505       81,081      136,000
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      TOTAL......................................   15,643,275   17,813,739   20,450,206   23,118,021   26,656,390   28,021,472   28,546,315   28,453,871   28,436,702   29,098,845   28,771,241
Interior/Superfund...............................  ...........  ...........       62,850       70,212       83,515       78,300       79,836       79,108       79,108       79,117       78,434
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      Total, Budget Authority....................   15,643,275   17,813,739   20,513,056   23,188,233   26,739,905   28,099,772   28,626,151   28,532,979   28,515,810   29,177,962   28,849,675
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Obligations for actual years exclude lapse. Includes funds for Type I Diabetes Initiative.
\2\ Fiscal year 2006--Comparable includes all comparable adjustments.


                                                              HISTORY OF OBLIGATIONS BY TOTAL MECHANISM \1\--FISCAL YEARS 1999-2008
                                                                                    [In thousands of dollars]
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                    Fiscal year
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                                                            2007         2008
                 Budget mechanism                                                                                                             2006 actual      2006       revised      revised
                                                       1999         2000         2001         2002         2003         2004         2005         \2\        comp.\3\      joint     President's
                                                                                                                                                                         resolution     budget
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Res. Project Grants..............................    8,779,019   10,118,249   11,557,511   12,995,051   14,239,043   15,165,836   15,426,097   15,313,663   15,332,997   15,417,256   15,080,819
Research Centers.................................    1,380,117    1,547,152    1,859,600    2,123,723    2,425,448    2,545,972    2,647,355    2,659,653    2,804,893    2,895,051    2,917,412
Other Research...................................      808,100    1,013,499    1,218,906    1,450,750    1,587,841    1,651,823    1,655,743    1,650,974    1,669,351    1,767,797    1,747,167
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal Res. Grants.......................   10,967,236   12,678,900   14,636,017   16,569,524   18,252,332   19,363,631   19,729,195   19,624,290   19,807,241   20,080,104   19,745,398
Research Training................................      509,185      539,510      589,624      650,686      711,441      740,506      743,861      731,121      748,641      771,600      769,413
R & D Contracts..................................    1,067,197    1,147,672    1,387,989    1,642,046    2,299,140    2,691,897    2,516,611    2,582,606    2,667,066    2,783,528    2,975,285
Intramural Research..............................    1,564,547    1,746,220    1,950,859    2,225,292    2,564,664    2,658,853    2,737,865    2,745,676    2,772,036    2,791,706    2,774,311
Res. Mgt. & Support..............................      542,188      600,203      690,929      786,647      927,297      977,771    1,014,754    1,098,953    1,108,615    1,132,127    1,142,492
Cancer Control...................................      306,734      389,425      459,482      501,208      533,173      529,980      531,634      505,705      505,705      516,565      516,565
Construction.....................................       32,734       76,181       78,000      117,600      496,782      118,148      178,560       29,700       29,700  ...........  ...........
Library of Medicine..............................      181,014      213,730      239,068      275,395      299,771      310,165      312,980      311,721      311,264      320,229      308,415
Office of the Director...........................      255,584      281,587      212,482      234,784      266,161      327,267      533,673      724,831      393,009      613,985      395,522
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      Subtotal...................................   15,426,419   17,673,428   20,244,450   23,003,182   26,350,761   27,718,218   28,299,133   28,354,603   28,343,277   29,009,844   28,627,401
Buildings & Facilities...........................      216,856      140,311      205,756      114,839      305,628      303,254      247,182      178,376       93,425       89,001      143,840
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      Total......................................   15,643,275   17,813,739   20,450,206   23,118,021   26,656,389   28,021,472   28,546,315   28,532,979   28,436,702   29,098,845   28,771,241
Interior--Superfund..............................       62,850       70,212       83,515       78,300       79,836       79,108       79,108       79,117       78,434
                                                  ----------------------------------------------------------------------------------------------------------------------------------------------
      Total Budget Authority.....................   15,643,275   17,813,739   20,513,056   23,188,233   26,739,904   28,099,772   28,626,151   28,532,979   28,515,810   29,177,962   28,849,675
------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
\1\ Obligations for actual years exclude lapse.
\2\ Fiscal year 2006 Actual Obligations include Interior (previously VA/HUD) Superfund activities within the Mechanism amounts.
\3\ Fiscal year 2006 Comparable includes all transfers and comparable adjustments.
\4\ B&F Budget Mechanism includes the B&F appropriation plus the following included in NCI: Fiscal year 2005--$7,936,000; fiscal year 2006--$7,920,000; fiscal year 2007 (est.)--$7,920,000;
  fiscal year 2008 (est)--$7,840,000.

Note.--All amounts include funds for Type I Diabetes Initiative.

                                 OPASI

    Question. I understand that you envision a significant role for the 
Office of Portfolio Analysis and Strategic Initiatives in future NIH 
activities. At present, the Office has a relatively small dedicated 
budget and workforce. Please provide us with an updated mechanism table 
for OPASI showing the enacted fiscal year 2007 enacted level and the 
fiscal year 2008 President's budget request. Please also provide 
narrative regarding your vision for OPASI's future role at NIH 
including, but not limited to, the following: The activities you 
envision OPASI performing.
    Answer. The Office of Portfolio Analysis and Strategic Initiatives 
(OPASI) is a policy office within the NIH Office of the Director. 
Related grant-making activities are carried out within the Common Fund/
Roadmap.
    The goal of the Office is to support the ICs in their collaborative 
efforts. OPASI accomplishes its mission through the efforts of three 
Divisions: the Division of Resource Development and Analysis, the 
Division of Strategic Coordination, and the Division of Evaluation and 
Systemic Assessments. These divisions work together to analyze the 
existing NIH research portfolio, collaborate with the ICs to plan and 
manage new research initiatives via the Common Fund, and provide 
evaluation support to the ICs so that future programs can be improved. 
The NIH has also established a Council of Councils (CoC) to give advice 
on OPASI activities. The CoC is composed of scientific and lay council 
members from the IC Advisory Councils and the NIH Council of Public 
Representatives who simultaneously serve on the CoC and their home 
councils.
    Division of Resource Development and Analysis: This Division 
develops tools, analyses, and resources that can be used within OPASI 
and in the ICs to monitor and report on spending in specific areas; 
performs portfolio analyses, particularly with respect to a wide 
variety of scientific areas in which multiple ICs are active; collects, 
distributes, and analyzes data on public health burden of disease as 
well as the impact of research on disease burden. One portfolio 
analysis tool being developed by this division, is the RCDC (Research, 
Condition and Disease Categorization system, formerly known as the 
Knowledge Management and Disease Coding system, KMDC) This system is a 
state of the art reporting tool that streamlines the process of 
identifying grants, contracts, and intramural research projects that 
are relevant to particular diseases, conditions, or scientific topics. 
The tool will first be used for category reporting for the fiscal year 
2010 budget.
    The RCDC use as a portfolio analysis tool for planning purposes 
will expand beyond OPASI to the ICs in fiscal year 2008 as personnel 
are trained in the use of the system.
    Division of Strategic Coordination.--This Division works closely 
with the ICs to manage the Common Fund, which funds the NIH Roadmap. 
Since many cross-cutting areas are funded through IC collaborations 
outside the context of the Common Fund, special criteria have been 
established for Common Fund initiatives. OPASI staff in this Division 
work closely with ICs to gather ideas for possible Common Fund 
initiatives, to determine the responsiveness of these ideas to the 
Common Fund/Roadmap criteria, and to prioritize the ideas based in part 
on analysis of current funding in these areas using tools from the 
Division of Resource Development and Analysis. Those areas not selected 
for Roadmap emphasis may be addressed through multi-IC collaborations 
outside the scope of OPASI management. Staff in this Division will also 
increasingly be involved in post-award management of Common Fund 
initiatives, reviewing progress of individual projects as well as 
providing an overall assessment of whether program goals and milestones 
are being met.
    Division of Evaluation and Systemic Assessments.--This Division 
manages the NIH portion of the PHS Evaluation Set-Aside funds and works 
with ICs to develop evaluation plans for their programs. In addition, 
the Division provides expertise for the evaluation of multi-IC-
supported programs, including those that are supported via the Common 
Fund. This activity will expand in future years to include an In-House 
studies team that will conduct evaluations of Common Fund/Roadmap and 
other trans-NIH programs. This Division also manages the coordinated 
development and submission of Systemic Assessment documents in response 
to the Government Performance Results Act (GPRA) and the Office of 
Management and Budget's Performance Assessment Rating Tool (PART).
    Question. Any grant-making or grant-administering activities you 
envision OPASI performing?
    Answer. A fundamental tenet of the Common Fund is that the 
initiatives should benefit and synergize with the missions of multiple 
or all ICs. The management of Common Fund initiatives is therefore 
inherently of interest to the ICs and is best served by highly engaged 
scientific program staff working in the ICs. For this reason, the 
grant-making authority and much of the grant administration of Common 
Fund initiatives lies in the ICs. However, IC staff work on individual 
initiatives that are of particular interest to their IC and therefore 
may not maintain perspective on the program as a whole. The role of 
OPASI throughout the process of Common Fund management is to provide an 
over-arching view and perspective of the Common Fund and the scientific 
goals that all of the initiatives are expected to meet. OPASI staff 
work on teams that consist primarily of IC staff to plan each of the 
initiatives, to review progress, to develop specific budgetary plans, 
and to develop evaluations for individual initiatives; their 
participation in all of the teams provides an overarching central level 
of management that insures that the trans-NIH nature of the initiatives 
is maintained.
    In addition to the Common Fund, OPASI oversees funding available to 
NIH from the PHS Evaluation Set-Aside. These funds are administered and 
managed by the Division of Evaluation and Systemic Assessment. The 
Division assesses funding requests from ICs for technical and 
conceptual merit as well as policy relevance. This is an internal 
process designed to ensure high quality program evaluations rather than 
a grant-making authority.
    Question. Broad strokes estimates for future growth of the office 
in terms of FTE's and budget (not including amounts appropriated 
separately for the Common Fund).
    Answer. OPASI future growth will occur in all three Divisions. 
Recruitment is underway in the Division of Strategic Coordination to 
allow central scientific staff involvement in all of the Common Fund 
initiatives. The current staffing level will be re-evaluated in fiscal 
year 2008 after the second cohort of initiatives is funded and while a 
third cohort is being planned to determine whether additional staff are 
needed in fiscal year 2009 and beyond. The Division of Resource 
Development and Analysis is expected to grow in fiscal year 2008 to 
accommodate increased portfolio analysis and planning both within OPASI 
and in the ICs. Its growth beyond fiscal year 2008 will involve the 
recruitment of staff to develop new tools to enhance the ability to 
plan for, assess, and manage complex portfolios and to expand the 
capacity to analyze Public Health Burden. The Division of Evaluation 
and Systemic Assessment will expand in fiscal year 2008 to increase the 
capability of doing evaluations in-house. FTEs are expected to grow 
consistent with the funds available for OPASI, currently funded at 
$7,826,000 (includes one-time funding of $4,550,000 for Research, 
Condition and Disease Categorization) in fiscal year 2007 to $4,450,000 
in fiscal year 2008, a decrease of $3,376,000 over fiscal year 2007.
                                 ______
                                 
             Question Submitted by Senator Daniel K. Inouye

                          BEHAVIORAL RESEARCH

    Question. Every year since fiscal year 1999, this Subcommittee has 
urged the NIH to support basic behavioral research and to find an 
organizational home for this activity. Basic research is the building 
block for subsequent discoveries that lead to improved treatments and 
cures. This, of course, is also true for behavioral research. How do 
you intend to ensure dedicated scientific leadership for basic 
behavioral research at the NIH?
    Answer. Basic behavioral and social sciences research (BSSR) is 
critical to the NIH mission and the Agency will continue to support 
work in these disciplines. We estimate that NIH support for basic BSSR 
has been over $1.0 billion annually since fiscal year 2004. NIA, NIDA, 
NICHD, NIMH and NIAAA have provided particularly strong funding in this 
area.
    The Office of Behavioral and Social Sciences Research (OBSSR), 
located within the Office of the Director, is key to leading, 
coordinating and participating in NIH BSSR activities, including basic 
BSSR. OBSSR participates in funding opportunity announcements developed 
by individual or small groups of Institutes and Centers (ICs) and also 
leads in the development of such initiatives. However, OBSSR does not 
fund initiatives directly or entirely and is dependent on individual 
ICs for support and funding of specific programs. The Office 
participates in the Genes, Environment and Health Initiative, the NIH 
Blueprint for Neuroscience Research, and the NIH Roadmap for Medical 
Research. It has taken the lead on several Roadmap initiatives, 
including RFA RM 07-004, Facilitating Interdisciplinary Research via 
Methodological and Technological Innovation in the Behavioral and 
Social Sciences (R21) (http://grants.nih.gov/grants/guide/rfa-files/
RFA-RM-07-004.html). Slated for funding in fiscal year 2007, this 
initiative seeks to foster better integration of the behavioral and 
social sciences with biomedical research with the ultimate goal of 
improving health.
    Under the leadership of its Director, Dr. David Abrams, OBSSR has 
recently completed a two-year strategic planning process that 
identified four major programmatic directions for the Office. As 
articulated in the Strategic Prospectus (http://www.conceptsystems.com/
OBSSR/OBSSR-Prospectus-final.pdf), the first programmatic direction is 
``next generation'' basic BSSR that will be informed by breakthroughs 
in complementary areas such as genetics, informatics, and multilevel 
analyses. Specific priority areas include but are not limited to the 
following:
  --Gene-Environment interactions.--How are genetic traits and early 
        life experiences linked to physical and emotional health later 
        in life?
  --Biosocial stress markers.--What are the biological sequelae of 
        stress, and how do they relate to long-term mental and physical 
        health?
  --Technology, Measurement and Methodology.--How can we improve 
        biomarker, behavioral and environmental data collection to 
        better understand pathways linking biology, behavior, 
        environment, and society?
  --Spirituality and health.--How do individual belief systems or 
        social religious norms affect health?
  --Work-related stresses.--How are conflicts between work and family 
        associated with social stress and health?
  --Social integration and social capital.--How have advances in 
        technology and mobility affected neighborhood social networks, 
        health behaviors and health outcomes?
  --Inequality and health outcomes.--How do large-scale societal 
        structures (e.g., racial segregation, immigration and 
        acculturation patterns, socioeconomic status) impact health?
    As a first step in the realization of ``next generation'' basic 
BSSR, OBSSR is currently leading a partnership among several ICs and 
the Centers for Disease Control and Prevention to issue new funding 
opportunity announcements to support behavioral and social science 
research on understanding and reducing health disparities (see http://
grants.nih.gov/grants/guide/notice-files/NOT-OD-07-063.html). The 
Office is also working with IC partners on activities to support 
research on gene-social environment interactions and in fiscal year 
2008 plans to sponsor a summer institute to train behavioral and social 
scientists in genetics/genomics.
    The senior leadership at NIH believes that the current NIH-wide 
approach of having basic BSSR within and across many ICs, and having 
OBSSR play a coordinating or leadership role, is the optimal 
arrangement for this area of research. Moreover, the NIH Reform Act of 
2006 established the new Division of Program Coordination, Planning, 
and Strategic Initiatives, of which OBSSR will be a part. This change 
will enhance OBSSR's coordinating and leadership roles, working in the 
new Division and with ICs to ensure the support of the highest quality 
basic and applied BSSR throughout the NIH.

                          SUBCOMMITTEE RECESS

    Senator Harkin. So, thank you all for being here. The 
subcommittee will stand in recess to reconvene at 3:30 p.m., 
Monday, March 26, in room SD-116.
    [Whereupon, at 3:05 p.m., Monday, March 19, the 
subcommittee was recessed, to reconvene at 3:30 p.m. Monday, 
March 26.]
