[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 2009

                              ----------                              


                        WEDNESDAY, JULY 16, 2008

                                       U.S. Senate,
           Subcommittee of the Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:47 a.m., in room SD-138, Dirksen 
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
    Present: Senators Harkin, Murray, Durbin, Reed, Specter, 
and Cochran.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF HON. ELIAS A. ZERHOUNI, M.D., DIRECTOR, 
            NATIONAL INSTITUTES OF HEALTH
ACCOMPANIED BY:
        FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR, NATIONAL HUMAN 
            GENOME RESEARCH INSTITUTE
        ANTHONY S. FAUCI, M.D., DIRECTOR, NATIONAL INSTITUTE OF ALLERGY 
            AND INFECTIOUS DISEASES
        ELIZABETH G. NABEL, M.D., DIRECTOR, NATIONAL HEART, LUNG, AND 
            BLOOD INSTITUTE
        JOHN E. NIEDERHUBER, M.D., DIRECTOR, NATIONAL CANCER INSTITUTE

                OPENING STATEMENT OF SENATOR TOM HARKIN

    Senator Harkin. Good morning. The Labor, Health and Human 
Services Appropriations Subcommittee will come to order.
    Welcome to our hearing on the fiscal year 2009 budget for 
the National Institutes of Health. Last year you'll recall that 
this subcommittee held six hearings. I promise we'll do it in 
2009, because I want to get back to that system of having all 
of the Directors back again, just--this year was just--a lot of 
things happening this year.
    Senator Cochran. You think you're going to be chairman 
again?
    Senator Harkin. Well, let me put it this way--even if I'm 
not chairman, I'll bet the--the way we pass this gavel back and 
forth, it won't make any difference. He'd let me have them 
anyway, even if I wasn't chairman.
    Anyway, we'll move on, here.
    Before I begin, I do want to take a moment to thank Dr. 
Collins, for his extraordinary service as a Director of the 
National Human Genome Research Institute. Dr. Collins has been 
teaching me about genomics since 1993 when he first came to 
NIH, and I'd like to think that, at times during those 15 
years, I almost understood what he was talking about.
    In fact, that's one of the things I admire the most about 
you, Dr. Collins. As brilliant as you are, you never talk down 
to your audience, you can converse as easily with the layman as 
with the Nobel Prize winner. In all the years that I've known 
you, I've ended entered a conversation with you without feeling 
smarter and more hopeful about the future.
    So, I think that that kind of a quality helps explain, 
again, why you were so successful in leading the Human Genome 
Project. An effort that, I believe, will go down in history as 
one of mankind's greatest achievements.
    This has also served you well during your 13-year crusade 
to pass the Genetic Information Nondiscrimination Act, which 
finally became law in May. They call it GINA, for short, we 
think it should have been called ``Francis'', for short.
    So, this will be Dr. Collins' final appearance before this 
subcommittee as the Director of the Genome Institute, but I 
strongly suspect that we'll see you here again in some other 
capacity, once you decide where and how you're going to apply 
your talents next.
    Until then, Dr. Collins, on behalf of this subcommittee, 
and I think I can speak for every person on this subcommittee, 
thank you for all you've done, at NIH and throughout your 
career, to help improve people's lives. You will be greatly 
missed.
    As for the matter at hand this morning, the NIH budget, we 
got some good news 2 weeks ago, when the President signed into 
law the supplemental that included $150 million for NIH. That's 
enough to award an additional 246 new research project grants, 
bringing the total for fiscal year 2008 to more than 10,000.
    Even with that increase, however, fiscal year 2008 marks 
the fifth 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 
10 percent in real terms. The average investigator now has a 
less than 1-in-5 chance of receiving an NIH grant. As Dr. 
Zerhouni has frequently lamented, the average age at which a 
researcher gets his or her first--R01 grant, is now 42.
    It should be no surprise, then, that many young people are 
deciding against a career in biomedical research, putting this 
Nation at risk of losing a generation of talented 
investigators.
    Regrettably, the President responded by freezing NIH 
funding in his fiscal year 2009 budget. Under his plan, the 
success rate for research project grants would fall to 18 
percent, the lowest level on record. But, rest assured, 
Congress will not accept this approach.
    Last month, the Senate Appropriations Committee marked up 
the fiscal year 2009 bill. It includes an increase of $875 
million over last year for NIH, on top of the $150 million in 
the recent supplemental.
    Today, Senator Specter and I will introduce another 
supplemental appropriations bill that would add $5.2 billion 
for NIH. This would be enough to restore the purchasing power 
of NIH that was lost to inflation since the end of the doubling 
period, plus provide $1.2 billion specifically for the National 
Cancer Institute, in line with the NCI's professional judgment 
bypass budget.
    To elaborate, perhaps, on this or anything else, I now turn 
to my distinguished ranking member and great friend, Senator 
Arlen Specter.

               OPENING STATEMENT OF SENATOR ARLEN SPECTER

    Senator Specter. Well, thank you very much, Mr. Chairman, 
and thank you for convening this important hearing.
    At the outset, Dr. Collins, I join the chairman in thanking 
you for extraordinary service. I thank all of you. I thank NIH, 
other medical professionals for the excellent care that I'm 
getting. As you can tell from my Telly Savalas look, I've had a 
recurrence of Hodgkin's. Had the last of 12 chemotherapy 
treatments on Monday. I'm constantly asked how I'm doing, and 
my slogan is tough, but tolerable. Good to have distractions so 
that I don't think about myself, and around here there are a 
lot of distractions.
    Senator Harkin. Why are you looking at me?
    Senator Specter. Senator Harkin and I--well, if I look at 
Senator Harkin, it's an attraction, it's not a distraction. Not 
as decisive as an attraction as looking at Senator Bettilou 
Taylor but also an attraction.
    Senator Harkin and I will be on the floor later today, as 
he's noted, with a supplemental appropriations bill for $5.2 
billion. Regrettably, the prospects are that it's confederate 
money, and we have to do something about it, it's just a 
scandalous situation to have seen the NIH budget cut in recent 
years, with across-the-board cuts, which we can't control, at 
all, out of the subcommittee.
    With the cost of living adjustments not maintained--again, 
which we can't control, because we've gone through the fat, the 
muscle and the bone, and there just isn't anything left in the 
subcommittee budget, when you have to compete with Headstart 
and worker safety and job training--the three departments which 
this subcommittee has. But we were determined, if I have a way, 
to do better.
    As you know, we have asked for projections as to what it 
would cost to cure cancer. Now, I hear everybody talk about 
cure, which is in quotation marks, but really make a major 
assault--a major assault.
    In 1970, President Nixon declared a war on cancer and had 
that war been pursued with the intensity of other wars, I 
wouldn't have gotten Hodgkin's and--we all have good friends 
who have died from breast cancer or prostate cancer, ovarian 
cancer--just rampant. We can do better. A lot better.
    Of course, you can't just move for the National Cancer 
Institute, there has to be parity with other NIH funding.
    We're taking a look at a collateral line, which may have 
some overlap on a funding stream, or may not. That is the issue 
of advanced directives. For some time now, Senator Harkin and 
I, in our subcommittee, have included in the request to 
Medicare to put in information on advanced directives. It 
hasn't worked out too well, and obviously, nobody should tell 
anybody else what ought to be done on that situation.
    I talked to the Secretary of Health and Human Services, 
Mike Leavitt, about it, and projecting the savings that might 
be obtained from advanced directives, the thought is there 
might be an incentive with a discount on part B payments. One 
of my colleagues, Senator Johnny Isakson, has an idea to make 
an advanced directive mandatory before coming into Medicare--
maybe that's too strong, but which way you go, it doesn't 
matter, if you take an advanced directive for life support, or 
not.
    We're trying to get a projection as to what we're doing--we 
just had a bloody political battle on Medicare, as you all 
know. Regrettably, we got it behind us, not with a lot of blood 
on the ground on the Senate chamber and from here to the White 
House, with condemnatory statements coming from the President 
yesterday about nine people who shifted their votes.
    I was asked about it, and what did I think about the 
President's veto, and the President's statement. I said, 
``Well, I respect the statement, I hope he would respect the 
Senators.'' We all have our constitutional role to play.
    But these are big, big issues which this committee is in 
the center of, and we've got the greatest experts around.
    As I told the chairman a few moments ago, I'm ranking on 
Judiciary, and there was a hearing that's going to start in 2 
minutes, and I have to be there for the opening part of it, but 
I will return very, very shortly for this important hearing.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you.
    Senator Durbin.

                 STATEMENT OF SENATOR RICHARD J. DURBIN

    Senator Durbin. I'm anxious to hear the testimony, but I 
wanted to be here today, first to thank Senator Harkin and 
Senator Specter--it really is hard to imagine that any of us 
could go home to our States and explain to the people of this 
country that we can not afford medical research.
    Yet, the fact is that after a dramatic increase in NIH 
funding, during the period when a Congressman from my State, 
John Porter, was chair of the appropriate House subcommittee, 
we have seen this whole area of medical research fall under 
this administration--not keeping up with medical inflation--let 
alone, inflation--in most instances. I think that that is 
shameful. I don't believe it's defensible, morally or 
politically.
    I want to thank Senator Specter and Senator Harkin for 
continuing their battle to fund this important agency.
    The major reason I'm here, and the questions I'll go to 
comes down to something that virtually every Senator faces, 
almost every day. When somebody comes in our office and says, 
``My son is dying, why aren't you spending more in research to 
find a cure for his disease? Why is the NIH spending so little 
for the research to spare him, and so many others who can 
die?''
    We sit here--I sit here--wondering--is that person right? 
Are we doing the right thing for medical research? Are we 
putting the money in the right places? I don't know the answer 
to that question, having been around Capitol Hill for a long 
time. I'm going to ask them that later.
    Thank you, Mr. Chairman.
    Senator Harkin. Senator Reed.

                     STATEMENT OF SENATOR JACK REED

    Senator Reed. Mr. Chairman, I too am here to thank and 
commend you and Senator Specter for your extraordinary 
leadership over many years. You've never let go of this issue, 
and you're responsible, collectively, for some of the vast 
improvements in NIH over many years.
    Let me also echo the concerns that Senator Durbin 
expressed, and one other, which is that it's not just about the 
relatively new therapeutic techniques. It's also maintaining a 
new generation of researchers and scientists. As this funding 
decreases we're seeing more and more of these very talented, 
young academic researchers go elsewhere.
    I had a chance to visit a Brown University researcher, Dr. 
Teresa Serio. She related to me that she was one of 30 Ph.D. 
students at Yale University--she's the only one now still in 
academic research, because the grants weren't there to support 
the applications to go forward, to get tenure, to do all the 
things you have to do. So, this is about the infrastructure of 
our research endeavor, and how it's also critical.
    Thank you.
    Senator Harkin. Thank you very much, Senator Reed.
    Senator Reed. I have a statement for the record, too, Mr. 
Chairman.
    Senator Harkin. Okay, it will be made part of the record.
    [The statement follows:]

                Prepared Statement of Senator Jack Reed

    Research to prevent debilitating diseases has the potential both to 
ease patient suffering and lessen the burden on our health care system. 
For this reason, I was proud to support the historic doubling of 
funding for the NIH from 1998 to 2003. Unfortunately, since then our 
Nation's commitment to this critical research has wavered.
    Recently, a group of concerned universities and research 
institutions--including Brown University in my State--released a report 
that documents how flat funding for the NIH puts a generation of 
science at risk. Since 2003, the purchasing power of the NIH has eroded 
by 13 percent. As a result, only 24 percent of research projects are 
funded, and the average age of first-time grant recipients is 43. The 
report finds that there is a real risk that we will lose aspiring 
scientists to other industries or overseas.
    Of course, flat funding puts at risk not only the development of 
scientists, but also their science--cures and treatments for chronic 
diseases that exact a costly human and economic toll. Rhode Island 
ranks 44th in the prevalence of chronic diseases such as cancer, 
diabetes, and heart disease. In 2003, the cost of treating these 
conditions was $1.2 billion and the economic cost in lost work and 
productivity was $4.5 billion. Obviously, an investment in research on 
these conditions would improve both the health of Rhode Islanders and 
the health of the Rhode Island economy.
    To show the real-life impact of stagnant funding, I want to tell 
you about Dr. Tricia Serio, a researcher at Brown University. Dr. Serio 
is ready to research ways to reverse the spread of proteins that damage 
the brain in several devastating diseases, including Alzheimer's, 
Huntington's, and Parkinson's. For years, the NIH said that her ideas 
were very innovative, but too risky. The NIH did not award her a grant 
until 4 years after she joined Brown.
    Dr. Serio has directly observed the effect of flat funding on her 
generation of scientists. She says that when she was at Yale, there 
were 30 Ph.D.s in her program; but she believes that she is the only 
one who is still pursuing a career in academic science.
    The NIH should not be forced to make the difficult decision to turn 
down research that is innovative, but risky. We did not send a man to 
the moon by being overly cautious. Nor will we discover a cure for 
cancer unless we make a significant investment.
    Mr. Chairman and Ranking Member, I am pleased that your bill 
increases funding by 3.5 percent to keep pace with biomedical inflation 
for the first time in 6 years. This is an increase of over $1 billion 
over last year and the President's request, which was extraordinarily 
shortsighted.
    I hope that we will pass this bill soon and that the President will 
reconsider his priorities. He should consider the stories of 
researchers like Dr. Serio, who are on the cusp of scientific 
breakthroughs, but desperately need our support.
    Thank you.

    Senator Harkin. Senator Murray.
    Senator Murray. I would just submit my statement for the 
record, I apologize for being a few minutes late. I really look 
forward to the testimony and opportunity to hear from all of 
you. I agree with everything I've heard this morning, that the 
investment's critical, the research is critical and just, to 
all of you, a lot of Americans, and people around the world's 
hope lands right in your lap as they are hoping that something 
that you discover or something that one of the scientists does 
changes their lives.
    So, we really appreciate the tremendous work you do, and 
are very proud of the support of this community, Mr. Chairman, 
I want to thank you personally for your attention to this.
    [The statement follows:]

               Prepared Statement of Senator Patty Murray

    Thank you, Senator Harkin and Senator Specter, for holding this 
hearing.
    I appreciate your long-time support for the National Institutes of 
Health. And I'm proud of this committee's leadership supporting 
research and other important health care issues.
    For more than a century, NIH has played a vital role in improving 
the health of our Nation.
    By conducting and supporting research on everything from breast 
cancer to autism, NIH is helping to improve our understanding of what 
causes diseases--so we can predict when they will occur and develop the 
tools to better fight them.
    Its work gives tremendous hope to the many Americans who suffer 
from a number of devastating diseases. And I believe that every dollar 
invested can save money later in reduced health care costs and economic 
productivity.
    That is why I have been extremely discouraged by President Bush's 
proposed funding levels for NIH.
    If President Bush's budget becomes reality, fiscal year 2009 will 
be the sixth year in a row that funding for the NIH was frozen at $29.3 
billion.
    That fails to keep up with biomedical inflation, and it would cause 
the projected success rate for research grant applications to fall to 
the lowest level since 1970.
    Fortunately, this year, we are taking steps to turn the tide.
    The Senate's Labor-HHS Appropriations bill increases NIH's budget 
by 3.5 percent, enough to keep up with inflation.
    While I wish we could do more, this is a step in the right 
direction.
    It has been almost 6 years since we increased NIH funding. In 
fiscal year 2003, when we doubled the budget, we enabled NIH to advance 
into new areas of science and to support far more promising research 
than ever before.
    Our continued investment will ensure that there are enough trained 
professionals ready to turn today's research advances into tomorrow's 
treatments, diagnostics, vaccines, and cures.
    And I look forward to working with my colleagues to continue 
support its progress.

    Senator Harkin. Thank you very much, Senator Murray.
    Again, Dr. Zerhouni, thank you very much, and thank all of 
you for being here today. Like I said, just because of 
schedules, this year I was unable to do what we did last year, 
and so I thought it was at least important to have you here to 
go over the budget and to respond to some of our inquiries, 
perhaps on what's happening at NIH, with the panel that you 
have in front of you, which represents the--perhaps the largest 
of the institutes at NIH.
    So, Dr. Zerhouni, again, welcome. Thank you for your great 
leadership, and please proceed as you so desire.

              SUMMARY STATEMENT OF HON. ELIAS A. ZERHOUNI

    Dr. Zerhouni. Thank you, Mr. Chairman, and members of the 
subcommittee. My colleagues and I are really pleased to be 
here, and we have submitted written testimony for the record, 
but what I'd like to do in my oral presentation is to really 
give you perspective about what has been the return investment 
which was testified to, over the years at NIH, in terms of 
benefits to the public.
    But today, what I'd like to stress is, in parallel to the 
difficulties we have to sustain momentum, there is an 
incredible opportunity that is facing us, that has come from 
the work of my colleagues, in particular, from the completion 
of the human genome.
    I would like to spend a few minutes with you, to describe 
for you what is it that NIH faces in terms of scientific 
challenge--you have the core issues that, from the scientific 
standpoint we see, that members of the subcommittee should 
focus on, and help us address.
    So, what I'd like to do, first and foremost is give you, if 
you'll allow me, a little lesson on the complexity of biology 
and where we're going.
    First and foremost, over the past 10 years, we have 
discovered methods, ways, approaches, ideas, technologies, and 
methodologies, that tell us that we can do four things we 
couldn't do before.
    One, we can be a lot more predictive about exactly how a 
disease develops, in whom it develops, and what are the markers 
that tell us that someone is susceptible to a disease process--
that's predictive.
    The second, we can be much more personalized about how we 
treat an individual, because we do realize today that none of 
us are exactly made like anyone else--we're individuals, and 
individual variability means that we have to tailor therapies 
to the individual.
    The third, for the first time in history, we can foresee an 
era where we can be preemptive, where we can act years before 
the disease strikes a patient, and basically keep the patient 
healthy, rather than wait for the disease to affect the 
patient, and for the doctor to intervene.
    So, we're moving from what we call a late intervention, 
reactive paradigm, to an early intervention, proactive 
paradigm, which will require the fourth P, which is 
participation.
    Now, participation is essential--Senator Specter is a 
fire--he really participates in his own care, and this is key 
to the success he's had in battling cancer.
    We see this as the future of medicine. Without 
understanding that, and I understand the future paradigm is 
very difficult to understand, but the strategies at NIH have 
been to advance our knowledge and to benefit the American 
public. See Figure 1.




                               Figure 1.

    So, let me just go forward here, and tell you the concept 
that is essentially emerging in front of us, and that is, the 
concept of complexity of disease processes.
    It is our understanding today that there's no disease that 
can--that comes from any one particular molecule in the body 
being diseased. In fact, most of us are a combination of a 
network of molecules, as described on the side, that interact 
constantly.

                  NORMAL GENE FUNCTION--HEALTHY STATE

    For example, here I have described five proteins--A, B, C, 
D, and E--all of these proteins are related to each other in 
the complex network. Over the past 50 years, since the 
discovery of the structure of DNA, what we have done is to try 
to understand how these proteins are interacting with each 
other. See Figure 2.




                               Figure 2.


    As we discover the genetic code, and we discover that, in 
fact, every protein in our body is really made through--by 
instructions that are embedded in our genetic code through a 
process of transcription and translation--then they understand 
that fundamentally to understand the healthy state, and the 
disease state, we need to understand the components.
    So, for example, in this case, A, B, C, D, and E are 
proteins that are encoded by DNA. So that, if you look at each 
one of them, you know that they are made upon instructions by 
DNA, and each one of them is made in a certain amount, a 
certain shape, and each one of them interacts with the other.

                 DISRUPTED GENE FUNCTION--DISEASE STATE

    So, what happens when a disease process occurs? One of the 
theories that we have worked on, over the past 25 years is 
that, perhaps, instead of having a concept of disease that is 
related to one protein creating one disease, perhaps what is 
more important is to understand how they all interact.
    But when we observe a disease process, we need to know 
which part of the code is abnormal? Where we do that, where we 
find, for example, what we have discovered over the past 5 
years, in great part due to the work of Dr. Francis Collins, is 
that when there is a bad instruction in our genetic code. For 
example, as I showed here with that little mark, what happens? 
Well, that instruction translates itself into a protein that, 
instead of being shaped normally, as a round circle, is now 
abnormal.
    So, what happens downstream in all of these molecules that 
keep us healthy, one of them will be abnormal, as you will see, 
that molecule now is completely misshapen. But that C molecule 
does not act by itself--it acts by interacting with A, and by 
repressing, for example, the amount of A, so the amount of A 
will increase. So on, we can see decreases in others. This is 
the disease state. See Figure 3.




                               Figure 3.

    So, the question we have faced over the past 15 years is, 
how can we discover all these code abnormalities, the things 
that we carry with us, that make us susceptible to disease, and 
how do we understand the environment interacting with it, in 
the context of a much more complex biology than we even thought 
in 1971. In 1971, we thought we would find silver bullets for 
cancer. Now we know that cancer is not one disease, not one 
pathway, not one interaction, but many. We need to understand 
them to be able to cure them.

                  GENOME-WIDE ASSOCIATION DISCOVERIES

    So, let me tell you, then, what happened in my tenure here 
as Director of the NIH since 2002--and in a slide provided to 
me by Dr. Francis Collins in 2005--how much we knew about these 
abnormalities in the genetic code that may have an impact on a 
particular molecule, or a disease process. See Figure 4. This 
is, basically, the discovery panel that I have in my office, 
trying to get the reports from everyone about what I was 
discovering in disease processes, according to that template 
that I showed you. That template is essential to comprehend, 
and it is essential to understand that, this is where the 
battle is, today, and this is where the resources need to be 
put in, and we do not have the resources to pursue all of these 
hints, if you will.




                               Figure 4.

    In 2005, what you see here are all of the chromosomes of 
the human body--all of these marks here are chromosomes. All of 
these chromosomes, essentially, are the genetic code. So, when 
you make a discovery, somebody puts a little flag on the 
chromosome and says, ``Gee, we made a discovery, here.'' 
Patients who have this disease, had this abnormality right 
there.
    In 2005, we found that in age-related macular degeneration, 
which is a major cause of blindness in our seniors, for years 
we thought it was a degenerative disease. Then, all of a 
sudden, someone discovered that the gene that was abnormal was 
an inflammatory gene, that led to the inflammation.
    So, all of a sudden, now, we have new treatments, because 
we have a completely new understanding of that complex network 
that I described.
    Look at what happens in 2005, and this is 2006: three more 
discoveries. See Figure 5. I was really elated, I thought this 
was great. Finally, we're breaking the code, we're going to be 
able to find some leads--then look what happens. First quarter 
of 2007, I had more discoveries reported to me than in the 
entire years of 2005 and 2006--that's the first quarter of 
2007. See Figure 6. Second quarter of 2007, I had even more 
discoveries than all of the cumulative discoveries that were 
made in my 5 years as NIH Director, just in the second quarter 
of 2007. See Figure 7.




                               Figure 5.




                               Figure 6.




                               Figure 7.

    In the third quarter of 2007, fourth quarter 2007, first 
quarter of 2008, and the second quarter of 2008. See Figures 8, 
9, 10, and 11. This is nothing short of an explosion of 
knowledge. This is not something that we can drop, this is not 
something that we can just leave on the floor and say, ``Our 
job is done.'' These are clues that tell us about dozens of 
diseases.




                               Figure 8.




                               Figure 9.




                               Figure 10.




                               Figure 11.

    For example, Type 2 diabetes--10 years ago, we knew about 
nothing, we knew zero genes that were important in diabetes. 
Many people had worked on it, couldn't find them. Five years 
ago, we have two genes, today 16 genes. I'm told in the next 
few days or weeks, a new paper is going to come up, identifying 
14 essential genes that underlie that network that I described, 
that is abnormal in diabetes.
    If you look at autism, last week--only last week, we 
received a report, a landmark report--identifying six new 
genes, and telling us something about this disease we didn't 
even know 3 years ago. So, the explosion is enormous, but does 
that mean our work is done?
    Actually, let me show you what we, as scientists, believe 
are great opportunities. I showed you genetic abnormalities in 
what we call our inherited genome, things that we're born with. 
But cancer is a different process. The genome of cancer can 
become abnormal during our lifetime.

          OPPORTUNITIES IN CANCER RESEARCH: NEW GENOMIC CLUES

    So, the National Cancer Institute and the National Human 
Genome Research Institute engaged in a program, a pilot project 
called the Cancer Genome Atlas, and guess what? Two weeks ago, 
they reported the first finding in one of the most deadly 
cancers, brain cancer, glioblastoma, and we reported three new 
genes, we had absolutely no idea that they were critical to the 
development of glioblastoma. See Figure 12.




                               Figure 12.

    This is happening in front of our eyes. Members of the 
subcommittee, I cannot tell you that the feeling I have is that 
we're witnessing, right in front of us, a revolution in 
knowledge. The question is, are we going to be able to take 
advantage of it? To take advantage of it is a rigorous process, 
that requires NIH to be extremely proactive, dynamic, flexible, 
and adaptive. But how?

                THE NEXT STEPS IN UNRAVELING THE MYSTERY

    Let me just show you with this slide what the process is. 
See Figure 13. Once you have a clue, like the many clues that I 
described, the first thing that you have to do is invest 
immediately in analyzing more populations and more genes, so 
that that clue becomes a real lead, so that you confirm it--not 
just one lab reporting a finding, you need two, three labs 
reporting that finding, so we can follow that lead. Just like a 
detective, you go after that lead. That's step one.




                               Figure 13.

    Once you have that lead, you need to understand, where does 
it fit in that complex network that I described--how does the 
biology work? Once you have understood the biology, now we have 
a real target to go after. So, you go from clue to lead to 
target, and then you have to make the investment to translate 
that into either diagnostics, a prevention strategy, or a 
therapeutic strategy, and we have done that in many diseases--
now we have a way to do it systematically in almost every 
common disease that we know.
    So, this is really the challenge, are we going to drop 
these clues? Drop these leads? Are we going to have the new 
next generation of scientists that are going to dedicate their 
lives in exploring what has come up through the 10 years of 
very hard work that all of us at NIH have done?
    The game is to transform medicine. We cannot practice 
medicine in 20 years the way we do today. It will have to 
change, otherwise, we will not sustain, the cost of healthcare 
that is facing us. It can only be done through renewed 
discovery, through renewed investments and trust that, in fact, 
only knowledge, only discovery will provide the solutions.

                          PREPARED STATEMENTS

    So, with that, I'd like to thank you, and again, repeat my 
admiration for Chairman Harkin, and ranking member Specter, and 
all members of the subcommittee, you've shown a deep 
understanding of the challenges in front of us, and we 
appreciate it very much.
    We're ready to answer your questions.
    [The statements follow:]

              Prepared Statement of Dr. Elias A. Zerhouni

    Good afternoon, Mr. Chairman, and distinguished members of the 
subcommittee. It is a privilege for me to appear before you today to 
present the National Institutes of Health (NIH) budget request and to 
discuss the priorities of NIH for fiscal year 2009 and beyond.
    Before I begin, please allow me this opportunity to express my 
appreciation to you and your staffs for your continued support of the 
National Institutes of Health.
    As you are aware, research is the basis of virtually every 
improvement in health and medicine. The impact of scientific research, 
however, extends far beyond disease. Throughout history, advances in 
science and technology strengthened our economy, raised our standard of 
living, enhanced our global leadership, and lengthened and improved our 
lives.
    To sustain these achievements, the flow of new scientific knowledge 
must be both continuous and substantive. Despite monumental progress, 
science remains a difficult frontier to explore. In this century, our 
society faces even greater challenges to the human condition that will 
require innovative and unprecedented scientific and technological 
advances across all fields of science, but most particularly in the 
life sciences. NIH's investment of $29.5 billion in fiscal year 2009 
will be used to support such advances.
    NIH plays a significant role in the extension of life, and the 
prevention and treatment of many diseases, transforming modern 
research, and medicine in countless ways. For example, not long ago, 
acute, short-term, and lethal conditions such as heart attacks, stroke, 
acute infections, and cancers were the dominant causes of early 
mortality. Today, life expectancy has markedly increased due to 
progress made in reducing death from such acute conditions. However, 
these advances indirectly led to a major rise in the burden of chronic 
long-term conditions. It is estimated 75 percent of today's healthcare 
expenditures relate to chronic diseases. The emergence and consequences 
of chronic conditions--like obesity, diabetes, or Alzheimer's disease--
are examples of the challenges we face. Healthcare costs are rising 
exponentially. We must continue our focus on not only how we best 
deliver healthcare, but more importantly, what healthcare we deliver.

                  A NEW STRATEGIC VISION FOR MEDICINE

    Given this dramatic shift from acute to chronic disease, the 
strategies for preventing and treating diseases are beginning to shift. 
Today, we intervene late when the patient exhibits symptoms of disease. 
Our research is changing this approach, so that we may intervene much 
earlier in the natural cycle of diseases, years before they strike 
their victims. We must now develop a much more pre-emptive approach 
that manages disease over its entire life cycle, from identifying an 
individual's susceptibility to a disease, to prevention, early 
diagnosis, reduction of complications, and smarter therapies.
    This shift from a late curative paradigm to an early pre-emptive 
one is becoming increasingly possible, thanks to the avalanche of 
recent discoveries funded by NIH. For example, in 2002, when I became 
NIH Director, we knew of one important gene abnormality in type 2 
diabetes. In the last year alone, researchers uncovered seven new genes 
or genetic regions that provide new clues to how this disease may 
develop. Remarkably, I now receive about one report a week of a 
significant discovery in the field of genomics. Recent discoveries 
apply to a broad spectrum of chronic diseases, ranging from mental 
disorders to autism. We now can see a clear path to what we call ``the 
4 P's of Medicine'': medicine that will be more Predictive, 
Personalized, Pre-emptive, and Participatory.
    To reach these key long-term goals, NIH is strategically investing 
in research to further our understanding of the fundamental causes of 
diseases at their earliest molecular stages. However, individuals 
respond differently to environmental conditions, according to their 
genetic endowment and their own behavior. In the future, research will 
allow us to predict how, when, and in whom a disease will develop. We 
can envision a time when we will be able to precisely target treatment 
on a personalized basis to those who need it, thereby avoiding 
treatment to those who do not. Ultimately, this individualized approach 
will allow us to pre-empt disease before it occurs, utilizing the 
participation of individuals, communities, and healthcare providers in 
a proactive fashion, as early as possible, and throughout the natural 
cycle of a disease process.
    This prospective management approach to disease is vital to the 
transformation of medicine of tomorrow. Today's discoveries are paving 
the way to make this future a reality. NIH continues its research 
efforts to search for cures to alleviate the suffering of the millions 
already affected by disease--and is greatly expanding the scope of 
research to discover entirely novel ways to stop disease in its tracks 
before it cripples us. This entails investing in completely new areas 
of investigation, while sustaining the level of our current efforts and 
supporting talented scientists using novel methodologies to explore new 
ideas and concepts that were impossible to envision only a few years 
ago.

          TODAY'S SCIENTIFIC ADVANCES ARE TOMORROW'S MEDICINE

    Consider how more predictive and personalized treatments could 
improve the safety and effectiveness of medications. The same 
medication can help one patient and be ineffective, or toxic to 
another. With the emergence of a field of research called 
pharmacogenomics, we will increasingly know which patients will likely 
benefit from treatment and which will not benefit, or worse, be harmed. 
Good examples of the present usefulness of pharmacogenetics are for 
cancer chemotherapy and use of the anticoagulant Coumadin.
    Research on viruses is improving the lives of Americans and people 
around the world. NIH supported the early research that led to the 
discovery and development of antiretroviral therapies for HIV/AIDS. 
Today, antiretroviral therapies are benefiting millions of Americans as 
the most effective means of treating HIV infections. These therapies 
are also helping millions of people in Africa and the Caribbean through 
the President's Emergency Plan for AIDS Relief.
    Current HIV/AIDS therapies focus on the virus itself. Researchers 
are trying to understand how the virus enters the human cell and 
hijacks the cellular machinery, so it can replicate and spread. In a 
recent experiment, researchers made significant progress toward 
reaching this goal. Their new approach is based on a process called RNA 
interference discovered in 1998 and recognized with a Nobel Prize in 
2006. Using RNA interference, the researchers suppressed the activity 
of every single gene in a type of human cell. They discovered more than 
276 human proteins that seem essential to the replication of the HIV 
virus in human cells. This experiment, unthinkable a few years ago, can 
now be exploited to develop new ways of disabling this deadly virus.
    Fundamental research can unexpectedly lead to revolutionary 
breakthroughs. Scientists at the National Cancer Institute, for 
example, developed a virus-like particle technology that formed the 
basis for new commercial vaccines that target specific cancers. In June 
2006, the U.S. Food and Drug Administration approved the vaccine 
Gardasil, which is highly effective in preventing infections from the 
four types of human papilloma virus (HPV) that cause the majority of 
cervical cancers in women. Worldwide use of this vaccine could save the 
lives of 200,000 women each year. This is the first example of a truly 
pre-emptive strategy in cancer.
    More often than not, it is the sustained combination of multiple 
approaches--from the most basic science to epidemiological and 
behavioral research--that makes advances in science effective. One 
important public health success story is the reduction in tobacco use 
and related diseases. In the last decade, overall cancer death rates 
dropped for the first time in a century, driven largely by the dramatic 
reduction in male smoking from 47 percent in the 1960s to less than 23 
percent today. This reduction, along with more effective early 
screening tools like mammography and colonoscopy, is changing the 
landscape of cancer mortality. These successes reflect the outcome of 
significant research investments made by many NIH Institutes and 
Centers (ICs) and our sister agencies over the last 50 years.
    Our ability to predict and pre-empt disease also hinges on the 
development of new diagnostics based on recent discoveries in genomics, 
proteomics, systems biology, and imaging. Among the diagnostic 
capabilities currently being explored are:
    Point of Care Diagnostic Testing.--NIH supports research that has 
and will develop technologies that offer instant diagnosis in the 
emergency room or physician's office, or at home, including rapid 
analysis of blood for assays such as chemistry, electrolytes and blood 
gases; biosensors that instantly detect signs of heart disease or 
infections; and biochips that detect disease processes at the molecular 
level.
    Salivary Diagnostics.--Scientists identified genes and proteins 
expressed in salivary glands that we believe will replace some forms of 
urine or blood analysis in the detection of cancer, heart disease, 
diabetes, and other conditions.
    Optical Imaging.--NIH-supported researchers are developing imaging 
techniques that seek to reduce the need for invasive diagnostic 
procedures. These new tools include fiber optic probes to detect 
malignant tissues, with the potential of avoiding invasive biopsies 
with a more accurate method of analysis; optical coherence tomography 
to identify heart disease; and multiphoton microscopy to study living 
cells and tissues.
    Brain-Wiring Diagrams.--NIH-supported researchers developed a way 
to reveal connections made by a single nerve cell in living tissue. We 
hope one day to construct a wiring diagram of the billions of nerve 
cells that constitute the brain's visual centers that might allow us to 
diagnose and treat vision loss with far more success--an advance that 
has implications for many other brain diseases as well.
    Autism Genes.--Research into autism discovered clues that rare 
genetic changes represent a risk for autism. With this preliminary 
result, we are on at least one path to understanding methods of 
predicting autism risk in infants.

                     THE CHALLENGES THAT LIE AHEAD

    We are optimistic about recent discoveries. However, there are 
challenges that lay ahead of us. We still need to focus much of our 
efforts on fundamental research, because new threats and diseases 
constantly emerge. For example, soldiers suffering from blast injuries 
highlight the importance of additional knowledge on traumatic brain 
injuries. Infectious diseases remain among the leading causes of death 
worldwide. More than 30 newly recognized infectious diseases and 
syndromes emerged in the last three decades alone, including HIV/AIDS 
and SARS. Infectious diseases that once seemed to be fading, such as 
tuberculosis and malaria, have resurged. New drug-resistant forms of 
once-easily treated microbial infections are emerging at a rapid pace. 
New strains of influenza occur each year. There is concern that a new 
influenza virus may emerge with the capacity for sustained human-to-
human transmission, possibly triggering a pandemic similar to what 
occurred in 1918, 1957, and 1968.
    The tragic events of September 11, 2001, and the deliberate release 
of anthrax in the Nation's capital, drove home the realization that 
certain deadly pathogens, such as smallpox or anthrax, could be used 
deliberately as agents of bioterrorism against the civilian 
population--similar to radiological, nuclear, and chemical threats. 
Research in these arenas is critical to meeting these threats, and $1.7 
billion is included in fiscal year 2009 budget for such NIH-supported 
research.
    Efforts to prevent, detect, and treat disease require better 
understanding of the dynamic complexity of the many biological systems 
of the human body and their interactions with our environment at 
several scales--from atoms, molecules, cells organs, to body, and mind. 
As the questions become more complex, and even as knowledge grows, 
research itself becomes more multi-faceted. We recognize that to 
effectively push science/new knowledge forward, researchers and 
scientists must begin to work more collaboratively to develop unifying 
principles that link apparently disparate diseases through common 
biological pathways and therapeutic approaches.
    Today, and in the future, NIH research must reflect this new 
reality. Advanced technologies, including sophisticated computational 
tools, and burgeoning databases, need to be more widely shared with 
easy public access. The scale and intricacy of today's biomedical 
research problems increasingly demand that scientists move beyond the 
borders of their own disciplines and apply new organizational and 
interdisciplinary models for science. One of NIH's most pressing 
challenges is to help generate and maintain the trained and creative 
biomedical workforce necessary to tackle the converging and daunting 
research questions of this century.
    Many of our public health problems have a behavioral component. To 
put evidence-based interventions into place, all of society must 
participate. To confront obesity, NIH researchers must continue to 
address a multitude of intersecting factors, from inherent biological 
traits that differ among individuals, to environmental and 
socioeconomic factors and behavioral factors that may have molecular 
and environmental influences. NIH developed innovative intervention 
programs such as the WE CAN (Ways to Enhance Children's Activity and 
Nutrition), now in several hundred communities. WE CAN is designed to 
help children maintain a healthy weight by promoting improved food 
choices, increased physical activity, and reduced screen time.
    NIH's primary mission is to develop new knowledge in biology and 
behavior and to apply this knowledge for the benefit of all. NIH is 
taking a more proactive role in helping to translate these discoveries 
into practice. For example, we have engaged in the most profound reform 
of translational and clinical research in the United States in over 50 
years. The NIH Common Fund (CF), a new clinical and translational 
science program, now supports 33 academic centers of excellence charged 
with the dual task of translating research from the laboratory to 
patients and discovering the most effective ways of implementing what 
we know best at the community level. Success in these endeavors depends 
heavily on our ability to train a new generation of clinician-
scientists steeped in modern methodologies and concepts of basic and 
translational research. This new generation of researchers must be able 
to work seamlessly with basic and applied scientists in an 
interdisciplinary environment.
    Through our ICs, NIH conducts many comparative effectiveness trials 
that provide evidence for more effective strategies of care. Many 
similar NIH-supported comparative effectiveness trials are uncovering 
evidence that shows, for example, that older generic drugs can often be 
as effective as newer medications in the treatment of high blood 
pressure (ALLHAT trial), or certain mental health disorders (CATIE 
trial). In order to disseminate these results, ALLHAT investigator-
educators made 1,696 presentations to 18,905 clinicians in 42 States 
and Washington, DC.
    Given the structure of our healthcare system, it is often difficult 
for providers to implement the evidence from these large NIH trials. 
This challenge is real and requires that all relevant parties work 
collaboratively toward a more systemic approach that goes beyond simply 
conducting more research of this type. All healthcare components must 
come together to develop clear follow-through mechanisms to implement 
the evidence generated by these large trials.

                    OUR NATION MUST SPUR INNOVATION

    With the NIH Reform Act of 2006 (Public Law 109-482), Congress 
provided a foundation for the centerpiece of the NIH Common Fund (CF) 
for Medical Research that provides ``incubator space'' to spur 
innovation. The CF supplies a centralized source of funding for trans-
NIH initiatives to meet the research and training needs of the 21st 
century and stimulate innovation. Research initiatives supported by the 
CF must not only be trans-NIH and fill a gap in our knowledge base but 
also be potentially transformative. The CF invests in systems biology, 
interdisciplinary research, biocomputing, and clinical research, all of 
which are fundamental to moving biomedical research forward 
expeditiously. The budget request includes $534 million for such 
activities.
    The Human Microbiome project is one such initiative. It promises to 
reveal how bacteria and other microorganisms that are found naturally 
in the human body (the ``microbiome'') influence a range of biological 
processes, including development, immunity, and nutrition. This effort 
will not only improve our understanding of how an individual's 
microbiome relates to disease, but will also support the development of 
new technologies and computational approaches--all cross-cutting 
outputs that can be applied to investigations of other biosystems.
    Another new initiative at the biomedical research frontier is the 
NIH Epigenomics Program. It will scan the human genome to study 
heritable features that do not involve changes to the underlying DNA 
sequence, but significantly affect gene expression and inform us about 
how DNA is regulated. This analysis of epigenetic changes should reveal 
new cellular pathways and mechanisms that influence disease 
progression. Also, the CF continues to support other important 
initiatives, such as the Pioneer Award program for $36 million in 
fiscal year 2009 which nurtures high -risk ideas that, if successful, 
can have unusually high scientific impact.
    Nurturing a new generation of innovators is critical to our future 
research endeavors. NIH makes strategic investments at every point in 
the pipeline to improve the flow of talent drawn from every part and 
population of America. We produce teaching supplements to help 
educators in grades 2 through 12 convey difficult concepts through 
engaging activities, improving health literacy, and hopefully sparking 
children's interests in careers in research. NIH offers undergraduate 
students research experiences, especially geared toward tapping the 
vast potential of young people from historically underrepresented 
groups in the sciences.
    NIH grants fund graduate students and post-doctoral fellows, who go 
on to fill most every niche in the American biomedical research 
enterprise--from academic research to private industry, and from 
venture capitalists to policy makers. But most importantly, young 
people need to see, at all stages of the pipeline, that biomedical 
research is an attractive career. They need to see that there is a 
stable research enterprise, providing them opportunities to explore 
their best ideas for improving human health. The budget request 
includes $123 million for individual fellowship awards under the Ruth 
L. Kirschstein program.
    NIH-supported scientists continue to discover the fundamental 
underpinnings of human biology in all of its complexity through 
investigator-initiated research, the mainstay of creativity in science. 
Thus, one of the top budget priorities is to sustain the number of 
competing Research Project Grants (RPGs). The budget funds essentially 
the same level of competing RPGs in 2009 as estimated in 2008--about 
9,760 RPGs at $3.5 billion. Overall, NIH will support nearly 38,260 
RPGs at $15.5 billion. This was accomplished, in part, by holding down 
inflationary increases for existing and new grants.
    One example of our efforts to sustain the research enterprise is 
the Director's Bridge Awards, which funded 244 scientists in 2007. It 
preserves the U.S. investment in investigators, laboratories, and the 
research projects that support our mission. We expect to continue this 
successful approach in 2009.
    Our priorities continue to focus on maintaining a competitive and 
viable scientific support system, especially for new and early-career 
scientists. Our long-term demographic projections show the aging of the 
Nation's scientific workforce. Unless we take an immediate and 
substantial proactive stance in protecting early-career scientists, 
this situation will have a negative and long-lasting impact on our 
competitiveness and innovation as a Nation. In 2007, we set a goal for 
the number of new career investigators based on the historic 5-year 
average of more than 1,500--it was surpassed. This represented a 
substantial increase in new career investigators over the number in 
2006 of 1,353. We plan to continue this commitment in 2008 and 2009.
    In 2007 and 2008 we also targeted earlier career stages, such as 
the Pathway to Independence Awards, supported by all NIH ICs. These 
awards provide 5 years of support for over 170 postdoctoral trainees a 
year to encourage risk-taking and independence. NIH plans to fund over 
350 postdoctoral scientists by the end of 2008 and continue the program 
in 2009. The budget request includes $56 million for the New Innovator 
Awards, which support newly independent scientists with novel ideas and 
potentially large scientific impact. Scientists must be within the 
first 10 years of receiving their doctoral degree to qualify. NIH 
funded 30 awards in 2007 and plans to maintain this promising program.

                PEER REVIEW AND TRANSFORMATIVE RESEARCH

    Peer review is such a fundamental and critical part of the research 
process that it requires our constant vigilance. With the increasing 
breadth and complexity of science, along with the increased number of 
research grant applications, NIH recognized the need to take a 
comprehensive look at its review process, and make the necessary 
changes to strengthen it for applicants and reviewers alike. Although 
our peer review system is outstanding--and emulated throughout the 
world--we wanted to make it even better
    In June 2007, NIH launched a comprehensive effort to identify 
information about the review process that could be used to enhance the 
agency's review system. Extensive input was sought and received from a 
wide range of stakeholders across the country and at NIH, which led to 
a comprehensive report released in February 2008 detailing the 
challenges facing our current system, and proposals for improvement. In 
June of this year, NIH announced the initiatives it plans to implement 
that should improve review efficiency and effectiveness. These can be 
grouped into four core priorities: (1) engage the best reviewers; (2) 
improve the quality and transparency of reviews with a greater focus on 
scientific impact while streamlining the application; (3) provide for 
fair reviews across career stages and scientific fields with a greater 
focus on early stage investigators and transformative research; and (4) 
develop a permanent process for continuous review of peer review.
    An important component of the new plan is an increased commitment 
to investigator-initiated high-risk, high-impact research to prevent a 
slowdown of transformative research, despite difficult budgetary times. 
I firmly support the need for NIH to invest in such research, even more 
so in times of restricted budgets. Examples are already under way such 
as the NIH Director's Pioneer award, the New Innovator Award, and the 
recently piloted EUREKA award program.
    To further stimulate this critical arena of research, NIH intends 
to continue to grow the Transformative Research portfolio. A key 
element in this portfolio will be the newly established investigator-
initiated ``transformative'' R01 program, funded within the NIH 
Roadmap. Potential impact and innovation will be the primary criteria 
for success in a review process that is designed to encourage risk-
taking to achieve revolutionary results. At the same time, NIH plans to 
continue the commitment for NIH Pioneer and New Innovator Roadmap 
awards and expand the current EUREKA awards to more ICs in the coming 
year. Taken together, these programs will represent a substantial 
investment in investigator-initiated transformative research.

                                SUMMARY

    At NIH, building toward the future involves innovations in multiple 
areas. We are in the midst of an explosion of new discoveries and novel 
opportunities for progress across all areas of science--from the most 
basic discoveries, such as the sequencing of the human genome, to the 
development of fields--like nanotechnology--that did not exist a few 
years ago. These advances have dramatically expanded the scope and 
capacity of the Nation's research enterprise, a goal and outcome of the 
doubling of the NIH budget.
    This remarkable growth in research capacity was accomplished, in 
part, by leveraging NIH and private sector resources to nurture more 
investigators, develop new technologies, and build infrastructure. The 
Small Business Innovation Research (SBIR) and Small Business Technology 
Transfer (STTR) programs, help entrepreneurs, as they translate science 
to market products to improve health and help maintain American 
economic leadership. A total of 4,350 new technologies were brought to 
market by 189 universities, hospitals, and private research 
institutions from 1998 through 2006. From 1980 to 2006, a total of 
5,724 new companies were formed around technologies developed by 
research institutions, many directly funded by NIH.
    The United States is now the pre-eminent force in biomedical 
research. Our Nation continues to lead the highly competitive 
biotechnology and pharmaceutical sectors. Yet, we are also the focus of 
increasing competition from growing research in Europe and Asia. NIH 
programs produce steady streams of novel discoveries and innovative 
researchers that flow into our industries, making them more 
competitive. We must continually sustain the momentum of U.S. 
biomedical research, or risk losing it. Complacency is unacceptable!
    We stand today at a crossroads in our efforts to improve health. 
Healthcare costs are rising. As a society, we must commit to moving 
forward and capitalize on the momentum created by advances in science 
and technology. We need to sustain this momentum. Progress in the life 
sciences in this century will be a major determinant of our Nation's 
health, its competitiveness, and its standing in the world. This is 
truly a race against time--a race that we cannot afford to lose.




                               Figure 1.




                               Figure 2.




                               Figure 3.




                               Figure 4.




                               Figure 5.




                               Figure 6.




                               Figure 7.




                               Figure 8.




                               Figure 9.




                               Figure 10.




                               Figure 11.




                               Figure 12.




                               Figure 13.

              Prepared Statement of Dr. Elizabeth G. Nabel

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Heart, Lung, and Blood 
Institute (NHLBI) of the National Institutes of Health (NIH). The 
fiscal year 2009 budget of $2,924,942,000 includes an increase of 
$2,830,000 over the fiscal year 2008 appropriated level of 
$2,922,112,000. The NHLBI provides leadership for a visionary and 
highly productive research program in heart, lung, and blood diseases. 
In December 2007, the Institute announced a new strategic plan to guide 
its next decade of research, training, and education to reduce the 
burden of the diseases under its purview. This statement describes the 
main elements of the plan and then focuses specifically on the 
Institute's many efforts to forge a scientific basis for a more 
personalized approach to medicine in the future and to translate 
research into practice.

                        THE NHLBI STRATEGIC PLAN

    Thanks to the dedicated involvement of the communities it serves, 
the NHLBI recently completed development of a scientific working plan 
to guide its activities and initiatives in the near future. The plan 
outlines goals that broadly reflect complementary and interactive 
avenues of scientific discovery--basic, clinical, and translational 
research. This crosscutting, versus disease-specific, approach 
highlights areas where the NHLBI is well positioned to make major 
contributions through investigator-initiated research and through 
programs that enable and supplement investigator-initiated activities. 
Shaping the Future of Research: A Strategic Plan for the National 
Heart, Lung, and Blood Institute is available on the NHLBI Web site at 
http://apps.nhlbi.nih.gov/strategicplan/, and printed copies have been 
distributed widely.
    In the area of basic research, the plan focuses on delineating 
normal and pathological biological mechanisms and exploiting the 
emerging understanding of them to identify biomarkers of disease. Such 
biomarkers--broadly defined as measurable indicators of genotype, 
normal or pathological processes, or responses to therapeutic 
intervention--will facilitate identification of disease subtypes and 
point the way toward new molecular targets for diagnosis, treatment, 
and prevention.
    The plan's clinical and translational research goals emphasize 
transmission of knowledge between basic and clinical research so that 
findings in one arena rapidly inform and stimulate research in others. 
More precise methods of diagnosing disease and predicting 
susceptibility and prognosis are expected to arise from application of 
new approaches from basic science laboratories. A critical challenge 
will be to develop individualized preventive and therapeutic regimens 
based on genetic makeup in combination with developmental and 
environmental exposures. Insights are already emerging, but robust and 
efficient means of validating both patient-focused and population-based 
treatments will be needed to establish an evidence base to guide 
medical practice.
    The plan acknowledges the need to enhance understanding of the 
processes involved in translating research into practice and to use 
that understanding to enable improvements in public health and 
stimulate further scientific discovery. It places particular emphasis 
on conducting research on primary prevention and identifying 
interventions that work in real-world health-care practice. As well, 
continued development and evaluation of new approaches to communicate 
research advances to the public is an important priority for ensuring 
full and informed participation of individuals in their health care.

              SETTING THE STAGE FOR PERSONALIZED MEDICINE

    Considerable progress has been made in reducing the burden of 
illness, particularly in the area of cardiovascular diseases, through 
development of therapeutic and preventive strategies that are broadly 
applicable to the general population at risk. Now we have advanced to a 
point where it may soon be possible to develop vastly more 
sophisticated approaches tailored to individuals. The dream is to be 
able to prevent disease entirely and, short of that, to be able to 
offer each patient a precisely targeted drug or other intervention, at 
a carefully titrated dose, for exactly the proper duration, without 
risking dangerous or troublesome side effects. One path to realization 
of this dream lies in developing a more complete and detailed 
understanding of the genetic basis of individual health and disease.
    Technological advances that make it possible to identify millions 
of DNA sequence variations rapidly and inexpensively, and to correlate 
them with individual characteristics and health indicators 
(phenotypes), have fueled an explosion of interest in this area. The 
NHLBI is investing substantial resources to move the science along, 
capitalizing on vast amounts of data gathered over many years from 
cohort studies such as the landmark Framingham Heart Study. In 2007, 
the Institute conducted genotyping using about 550,000 SNPs (single-
nucleotide polymorphisms, which are tiny variations in the DNA code) in 
over 9,300 people from three generations of Framingham study 
participants. The genetic data are being linked to an array of 
phenotypic information, including major risk factors such as blood 
pressure, serum cholesterol, fasting glucose, and cigarette use; 
biomarkers such as fibrinogen and c-reactive protein; 
electrocardiography measures; imaging measures that reveal nascent 
pathology; and data on clinical cardiovascular disease outcomes. The 
resulting research resource, known as the Framingham SHARe (SNP Health 
Association Resource), is being developed and maintained by the NIH 
National Center for Biotechnology Information in its Database of 
Genotype and Phenotype (dbGaP). This rich source of data will be made 
available--with appropriate privacy safeguards--to qualified 
investigators at no cost.
    The Framingham SHARe is only the first of many NHLBI efforts to 
enable what are known as genome-wide association studies (GWAS)--
projects that involve scanning markers across complete sets of DNA from 
many individuals to find genetic variations associated with diseases or 
conditions of interest. The Institute is moving rapidly to increase the 
diversity of its genotype-phenotype data resources. Thus, we have 
created the MESA SHARe, based on cohorts from the Multi-Ethnic Study of 
Atherosclerosis, a long-running multicenter study that includes 
Americans of African, Chinese, Hispanic, and European ancestry. The 
SHARe-Asthma Resource project or SHARP is conducting a genome-wide 
analysis in adults and children who have participated in NHLBI's 
clinical research networks on asthma. The Candidate-gene Association 
Resource or CARE project includes plans to genotype one million SNPs in 
African-American men and women and link the results with phenotypic 
data obtained from eight major epidemiological studies, including the 
Cooperative Study of Sickle Cell Disease and the Sleep Heart Health 
Study. The NHLBI has also undertaken genotyping of African-American 
women who participated in the Women's Health Initiative, a project of 
great interest to many NIH components and the communities they serve.
    The GWAS approach offers a powerful and unprecedented avenue to 
unravel the contribution of complex traits to common diseases, and it 
is clear that the richness of the data generated from these studies is 
far greater than could be explored by a single investigator or group of 
investigators. To ensure that the greatest possible public benefit 
accrues from our investment in GWAS, under terms and conditions 
consistent with the informed consent provided by research participants, 
the NIH has established a GWAS data-sharing policy for NIH-supported 
investigators (http://grants.nih.gov/grants/gwas/). I was pleased to 
lead my NIH colleagues in this effort and, now, I am honored to serve 
as co-chair of the NIH Senior Oversight Committee for GWAS studies. I 
believe that robust NIH leadership in all aspects of GWAS will enable a 
superior yield from this exciting approach and bring us closer to 
realizing the dream of personalized medicine.

              PHARMACOGENOMICS MOVES CLOSER TO THE BEDSIDE

    The long-term vision of creating a broad selection of custom-made 
therapies for individualized treatment is tantalizing, but a great deal 
of work needs to be done before it can be achieved. Much closer to 
near-term application is the use of pharmacogenomics--an understanding 
of how genetics explains individual differences in response to drugs--
to guide prescribing decisions for agents currently on the market. A 
case in point is the use of the anticoagulant warfarin, a tricky drug 
to prescribe because too little or too much can produce serious 
problems and the dose requirement varies widely from one patient to 
another. Research has identified two specific genetic variations that 
appear to account for much of the inter-individual variation in 
sensitivity to warfarin, and we are now moving forward with a clinical 
trial to evaluate the clinical efficacy of a genotype-guided 
prescribing strategy for warfarin therapy and to determine whether the 
increment in efficacy and safety warrants the cost of genetic testing. 
We fully expect that genetic stratification of patients will become the 
norm for trials to evaluate new drugs, and that genetic information 
will prove invaluable for the design of novel alternatives to existing 
drugs that are likely to be ineffective or harmful in genetically 
susceptible individuals.

                     BRIDGING RESEARCH AND PRACTICE

    In the upcoming years, these and other research efforts will yield 
an extraordinary amount of new information that will fundamentally 
transform medical practice and call for innovative approaches to 
translation and dissemination. We must be prepared to make the most of 
it. In line with its strategic plan, the NHLBI has developed a new 
knowledge network approach to bridge the gap between discovery and 
delivery, identify areas that should be addressed by future research, 
and develop more effective approaches for synthesizing and organizing 
scientific evidence and moving it into practice. The first network, 
addressing cardiovascular diseases, will be implemented globally and 
make innovative use of new media technologies.
    The NHLBI has also begun a new effort to develop comprehensive, 
evidence-based, integrated guidelines to assist primary care physicians 
in helping adult patients reduce their risk of cardiovascular diseases. 
The integrated approach will focus on all cardiovascular risk factors 
to reflect the complicated clinical scenarios that patients and 
physicians typically face. Expert panels are being convened to review 
available scientific evidence and update existing guidelines for the 
prevention, detection, evaluation, and treatment of high cholesterol, 
hypertension, and overweightness/obesity. An important goal of both the 
integrative guidelines and the updates is to improve implementation, 
especially among high-risk and minority communities. Ensuring that the 
public benefits from its investment in biomedical research is, and has 
always been, our highest priority.
                                 ______
                                 
             Prepared Statement of Dr. John E. Niederhuber

    Mr. Chairman and Members of the Committee: Thank you for the 
opportunity to offer testimony on behalf of the National Cancer 
Institute (NCI) and the National Cancer Program. The fiscal year 2009 
budget of $4,809,819,000 includes an increase of $4,731,000 over the 
fiscal year 2008 appropriated level of $4,805,088,000.

                       A UNIQUE NATIONAL RESOURCE

    At his hometown hospital, the patient remembers, ``there were lots 
of debates and lots of questions about what I really had. They really 
didn't know.'' His condition was rare, and its identity remained 
elusive. Ultimately, one doctor made a simple promise: ``I'm going to 
find somebody in this country that knows a lot more about this.'' And 
so he did. Ten years ago, the patient headed to the National Institutes 
of Health Clinical Center in Bethesda, Maryland and a research study 
lead by Dr. Wyndham Wilson at the National Cancer Institute. The 
condition turned out to be Lymphomatoid Granulomatosis, a rare, 
progressive disorder of the lymph nodes and blood vessels that can, 
over time, involve the lungs, skin, kidneys, and central nervous 
system. ``If you look at the published literature on my disease,'' the 
patient says, ``it's a very high mortality rate. What the NCI's 
treatment regimen has done is completely turn that around. They're 
doing things that other people just aren't doing, and then sharing it 
and disseminating it throughout the world.'' The patient remained in 
remission for 9 years. Last fall, when his disease returned, the 
patient returned to Dr. Wilson's care with his optimism intact. ``These 
people at the NIH are so talented, so kind--and they're doing this just 
to help people and advance learning so that other people can benefit 
from their work around the country. They're an amazing group of 
people.''
    Our patient's cancer story is not finished. Neither is the work of 
the National Cancer Institute. The NCI is striving for a time when the 
life stories of millions of patients will no longer end with cancer. 
For several years now, scientists who devote their careers to the study 
of cancer have spoken, with increasing frequency and enthusiasm, about 
their hopes for an era of ``personalized medicine,'' when cancer will 
be treated as a chronic condition--not the killer it is today. Spurred 
by the completion of the landmark Human Genome Project, we have begun 
to realize a vision of cancer prevention, early diagnosis, and targeted 
treatment based on each patient's tumor and unique genetic make-up. In 
time, this knowledge will be linked to cancer risk and the earliest 
cellular changes that lead to development of a malignancy--years before 
tumor formation or symptom onset.
    Today, cancer researchers are using new molecular technologies, 
such as whole genome scans and actual sequencing of patients' tumors, 
searching for abnormal proteins in individual patient's body fluids 
that are the result of these genetic changes. As a result, scientists 
are studying an ever-growing group of targeted therapies, which attack 
cancer cells but leave healthy tissue untouched.
    Scientists have also learned the critical importance of the 
microenvironment of tissue surrounding the tumor, and they have 
elucidated the essential ways in which these cells--connective tissue 
cells, new blood vessel cells, and cells of the immune system--support 
the growth and metastasis of the cancer. Scientists have increasingly 
identified ways in which these non-cancer cells can also be targeted, 
to block tumor progression. Recognizing the complexity of a cancer and 
of its progression to a fatal disease, researchers have come to the 
understanding that our treatments will not be simple; complex therapies 
will help fight a complex disease. Without a doubt, science and the 
technology that supports research are making progress against cancer at 
a pace never before seen.
    America's Federal investment powers--and empowers--the engine of 
cancer research. The National Cancer Institute, as the leader of our 
National Cancer Program, funds thousands of researchers (5,713 in 2007) 
at hundreds of our great research universities and Cancer Centers from 
coast to coast--along with a cadre of Government scientists based at 
the clinical center on the campus of the National Institutes of Health 
who, like Wyndham Wilson, conduct the kind of high-risk science 
unlikely to be found elsewhere.
    Clearly, the Nation's investment is paying dividends. There are now 
almost 12 million cancer survivors in America. Today's cancer research 
shows great promise to reduce the personal and financial costs 
associated with cancer, which, according to the American Cancer 
Society, totaled $206.3 billion in the United States in 2006. However 
of great worry, cancer is a disease of aging, the result of a lifetime 
of genetic alterations, additions, and subtractions that accumulate in 
our genes and impact their function. With a rapidly aging population, 
NCI estimates that the total economic burden of cancer in the United 
States will increase to $1.82 trillion by 2017.\1\ This clearly 
underscores the urgency of increasing our investment in cancer 
research.
---------------------------------------------------------------------------
    \1\ National Cancer Institute, Estimates of the National Economic 
Burden of Cancer for 2007 and 2017, April 17, 2007.
---------------------------------------------------------------------------
    NCI's progress against cancer is evident across its vast research 
portfolio:
  --Genome-wide association studies are revealing increasing numbers of 
        genes that may contribute to cancer risk. These high-tech 
        studies compare large groups of people: one group with a 
        disease and one without, searching for abnormal genes, which, 
        once validated and further studied, will lead to strategies for 
        prevention, enhanced early cancer detection, and novel highly 
        targeted treatments.
  --The NCI Community Cancer Centers Program, now in a 3-year pilot 
        phase at 16 sites across the country, is studying how best to 
        bring state-of-the-art, multi-specialty cancer care, electronic 
        medical records, and early-phase clinical testing of new 
        therapies to patients in their own communities, because access 
        to scientific advances is an essential factor in decreasing 
        cancer mortality and healthcare costs.
  --The cancer Biomedical Informatics Grid (caBIGTM) is a 
        21st century information initiative connecting cancer research 
        and clinical trials--both public and academic--from coast to 
        coast. caBIG is an essential program to address the new era of 
        highly personalized medicine and the rapid translation of 
        discovery to practice.
  --Expanding deployment of Electronic Health Records linked to 
        clinical research can provide security and portability for 
        patient health and medical information.
  --Pioneering a new kind of early clinical trial, which looks at small 
        numbers of patients and uses extremely small quantities of 
        investigational medications and high-technology imaging, to see 
        if the drug reaches its molecular target. Phase 0 trials have 
        the potential to shorten drug development and reduce costs by 
        millions of dollars.
  --NCI's expanding platform of new drug development actively links 
        university scientists with the complex enterprise of novel 
        agent chemistry, validation, and the final steps of private 
        sector translation.

                      CANCER AS A MODEL OF DISEASE

    Cancer has long been a model for the study of disease in the 
laboratory and a model of healthcare in the community. For example, 
knowledge about how tumors form new blood vessels (angiogenesis 
research), has contributed to our understanding of macular 
degeneration, diabetes, wound healing, and ischemic heart disease. In 
fact, the Nation's investment in cancer research has affected the 
diagnosis and treatment of most major diseases. Cancer is the only 
disease for which tissue is routinely collected for study in the 
laboratory. Having malignant, pre-malignant, and normal tissue from the 
same patient allows researchers in many fields to understand the 
biology of pathologic disease processes, at the cellular level. The 
ability to perform tissue analysis also makes cancer patients the most 
highly characterized population of patients with chronic disease. 
Physicians are now using these data to inform prevention and treatment 
schemes tailored to the individual. The NCI recognizes that 
characterizing the patient and delivering state-of-the-art care in the 
community setting is the model for future healthcare delivery. We are 
continually studying ways to optimize this approach.

                          SUPPORTING RESEARCH

    The backbone of America's cancer research enterprise is the 
individual investigator working at a laboratory bench, conducting 
hypothesis-driven science. These scientists are also the academic 
faculty who train and guide the next generation of researchers. 
Understanding those dual values, NCI is working to reassign resources 
to provide a stable level of financial support for Principal 
Investigators.
    NCI is also pushing to reinvigorate its intramural program, 
comprised of the Government scientists who study types of cancer 
unlikely to be addressed by the private sector and whose research 
encompasses high-risk science that has the potential to greatly advance 
our knowledge of cancer and its processes.
    One of the greatest services NCI can offer the Nation is to help 
foster a dedicated cancer research workforce for the future. We have 
placed more emphasis on carefully reviewing and more-aggressively 
funding new applications from young scientists. We are working to bring 
more young scientists to Bethesda for day-long meetings and 
interactions with NCI staff. Moreover, because a grant from NIH is 
often a pre-requisite for obtaining and keeping academic tenure, NCI is 
developing plans to mandate a mentoring committee at each new 
investigator's home university.

                          WORKING FOR PATIENTS

    When she arrived at the NIH Clinical Center, our patient couldn't 
even make a fist. Her hands, wrists, elbows, hands, and knees could 
scarcely bend. A once-vibrant woman in her late 20s, she was now 
severely anemic, wheelchair bound, and wrapped in blankets to preserve 
the body heat her skin could no longer retain. Over 2 years, as she 
suffered the disabling manifestations of cutaneous T-cell lymphoma, she 
spent more nights in the hospital than at home. She was in hospice care 
and lacked the strength to be with her two small children. She came to 
the Clinical Center virtually out of treatment options--and once there, 
an initial short list of experimental treatments had all failed. Having 
apparently run out of all hope, our patient came into the care of Dr. 
Martin E. Gutierrez, a staff clinician with the NCI's Medical Oncology 
Branch. Dr. Gutierrez, who has spent his career working on new 
therapies for T-cell lymphoma patients, tried a new drug being 
developed through NCI's Rapid Access to Intervention Development (RAID) 
program. RAID exists to speed the translation of novel anticancer 
therapies from laboratories to patients. And in this case, the new drug 
paid off dramatically. Within the first few doses, Dr. Gutierrez began 
to see improvement. Within 7 months, the patient's symptoms were gone. 
Today, more than a year after her arrival at the Clinical Center, the 
patient's tests show no evidence of disease.
    NCI will not rest until such stories are commonplace. Our Nation's 
investment in cancer research is paying dividends--in lives saved, in 
greater quality of life for cancer patients, and in cancers prevented. 
The National Cancer Institute is dedicated to a future in which cancer 
is no longer the killer we know today, but a condition most often 
prevented, or else treated effectively, with minimal side-effects. The 
future of medicine is personal. Our country's investment in that future 
is vital. Everything we do at NCI begins and ends with real people: 
those with cancer, those at risk for the disease, and those who care 
for them.
                                 ______
                                 
              Prepared Statement of Dr. Francis S. Collins

     Mr. Chairman and Members of the Committee: I am pleased to present 
the fiscal year 2009 President's budget request for the National Human 
Genome Research Institute (NHGRI). The fiscal year 2009 budget includes 
$487,878,000; an increase of $1,099,000 from the fiscal year 2008 
enacted level of $486,779,000.
    NIH's investment in the Human Genome Project (HGP) and the 
International HapMap Project have moved us closer to a future that uses 
genomic information to diagnose, treat, and prevent disease.

                       DISEASE-GENE ASSOCIATIONS

    The HapMap has introduced a new paradigm to genomic research, 
primarily in the form of genome-wide association studies (GWAS), 
enabling cost-efficient assessment of much of the common genomic 
variation within an individual. The GWAS approach is novel in that it 
surveys the genome comprehensively and without preconception as to the 
relationships between genetics and disease, whereas earlier research 
efforts were largely focused on candidate genes thought to be 
associated with specific diseases. The innovative GWAS approach allows 
for the identification of genes involved in common diseases, 
contributing to a better understanding of the development and 
progression of common diseases, and pointing to follow-up research that 
may lead to improved diagnostic, therapeutic, and preventive 
approaches.
    With unprecedented speed, researchers have applied GWAS to identify 
a stunning number--over 70 in 2007 alone--of genetic factors associated 
with the most common causes of morbidity and mortality in the United 
States, such as diabetes, cardiovascular disease, obesity, cancer, and 
multiple sclerosis. Identification of gene variants associated with 
disease raises the possibility of using genetic testing, in combination 
with family history information, to identify susceptible, pre-
symptomatic subjects for screening and preventive therapies. The pace 
of disease-gene discovery is likely to accelerate even further over the 
next 2 or 3 years due to the completion in 2007 of the second-
generation map of human genetic variation (Phase II HapMap). This 
updated and powerful tool allows researchers to identify variations 
associated with disease even more quickly and accurately.

           APPLYING NEW KNOWLEDGE ABOUT THE GENOME TO HEALTH

    The NHGRI has increasingly directed the power of its large-scale 
sequencing program, which fueled the completion of the Human Genome 
Project, toward the long-range objective of making human DNA sequencing 
a tool for both research and medical practice. New directions include 
obtaining genomic sequence data from many individuals with various 
physical traits and disease states--data that will prove critical for 
addressing a wide range of questions important for advancing 
biomedicine. To move these advances more rapidly into clinical care, in 
2007 the NHGRI established the Genomic Health Care Branch within its 
Office of Policy, Communication, and Education. The new branch's 
mission is to help facilitate the translation of genomic research into 
advances in clinical medicine, especially in the primary care setting.

                        THE CANCER GENOME ATLAS

    The Cancer Genome Atlas (TCGA) is a joint NCI-NHGRI effort to 
accelerate understanding of the molecular basis of cancer through 
application of genome analysis technologies. TCGA began in 2005 with a 
3-year, $100 million pilot project to determine the feasibility of a 
full-scale effort to explore the universe of genomic changes involved 
in all human cancers.

                          THE HUMAN MICROBIOME

    There are more bacteria in the human gut than cells in the entire 
human body. Furthermore, microbes in the gut, skin, oropharynx, and 
vagina have a profound effect on many human physiological processes, 
such as digestion and drug metabolism, and play a vital role in disease 
susceptibility and even obesity. The Human Microbiome Project, 
conducted under the auspices of the NIH Roadmap Project and co-led by 
the NIAID, NIDCR, and NIDDK, represents an exciting new research area 
for the NHGRI.

          TECHNOLOGY ADVANCES, ON THE WAY TO THE $1,000 GENOME

    In August 2007, the NHGRI awarded grants to advance the development 
of innovative sequencing technologies intended to reduce even further 
the cost of DNA sequencing and expand the use of genomics in biomedical 
research and health care. With NHGRI support, excellent progress has 
been made toward both the near-term goal to lower the cost of 
sequencing a mammalian-sized genome to $100,000, and the longer-term 
goal of $1,000 or less. Further grant awards in this area will be 
announced in late summer 2008.

               CHEMICAL GENOMICS AND MOLECULAR LIBRARIES

    The chemical genomics initiative, part of the NIH Roadmap, offers 
public sector researchers access to high-throughput screens to test 
small organic molecules for potential uses as research tools. This 
initiative will even help expedite the development of innovative drugs 
for rare diseases, by demonstrating how early stage compounds interact 
with novel molecular targets. This program provides direct translation 
of genomic medicine by identifying small molecule drug-like compounds 
that can be used as starting points for new treatments, or as new 
applications of that agent. A dramatic example is the recent 
identification of a compound that shows great promise for the treatment 
of schistosomiasis, a parasite disease affecting more than 200 million 
people in Africa, Asia, and the Middle East.

                         KNOCKOUT MOUSE PROJECT

    The technology to ``knock out,'' or inactivate, genes in mouse 
embryonic stem cells has led to many insights into human biological 
processes and human disease. However, information about knockout mice 
has only been published and made available to the research community 
for about 20 percent of the estimated 20,000 mouse genes. Recognizing 
the wealth of information that mouse knockouts can provide, the NHGRI 
launched a trans-NIH, coordinated, 5-year cooperative research plan 
that, in cooperation with European and Canadian programs, will produce 
knockout mice for every mouse gene and make these mice available as a 
resource to the entire community.

                              1000 GENOMES

    The 1000 Genomes Project is an international research project that 
will sequence the genomes of at least a thousand people from around the 
world to create the most detailed and medically useful picture to date 
of human genetic variation. The 1000 Genomes Project seeks to produce a 
publicly available catalog of variants that are present at 1 percent or 
greater frequency in the human population across most of the genome.

                                CLINSEQ

    The purpose of ClinSeq, an intramural NHGRI research initiative, is 
to pilot large-scale medical sequencing (LSMS) in a clinical research 
setting and to investigate some of the technical and medical issues 
that accompany the implementation of LSMS in clinical settings. 
Currently, ClinSeq is recruiting 1,000 participants across the spectrum 
of risk for coronary heart disease (CHD). Relationships between 
patients' genetic makeups and observed phenotypes will be explored to 
better understand how variations in genes relate to cardiac health 
status.

                               MULTIPLEX

    The NHGRI and the NCI have teamed up with Group Health Cooperative 
in Seattle and Henry Ford Health System in Detroit to launch the 
Multiplex Initiative, a prospective study that is enrolling young, 
healthy adults to learn how they react to the offer of genetic testing 
for a panel of 15 genes linked to 8 common conditions. The study will 
follow individuals who decide to have the testing to see how they 
interpret and use the results in making future health care decisions. 
This study should provide insights that will be important to advancing 
the realization of personalized medicine.

                    ENCODE (SCALE UP AND MODENCODE)

    We are continuing to expand the ENCyclopedia Of DNA Elements 
(ENCODE) project, a research consortium that, in its pilot phase, 
yielded provocative new insights into the organization and function of 
the human genome. The NHGRI is moving forward with a full-scale 
initiative which should provide a more comprehensive picture of the 
biological roots of human health and disease. We are also engaged in a 
new effort, called the model organism ENCODE (modENCODE), to apply many 
of the ENCODE methods and technologies to the genomes of the roundworm 
and fruit fly model organisms, to inform our efforts to understand how 
the human genome functions.

          MINORITY OUTREACH ACTIVITIES AND HEALTH DISPARITIES

    The NHGRI remains at the forefront of ensuring that minority 
scientists and students are equipped to meet the challenges of genome 
research in the 21st century. With support from the NIH Director and 
several Institutes and Centers, the NIH has created the NIH Intramural 
Center for Genomics and Health Disparities (NICGHD) within the NHGRI 
Division of Intramural Research, with a mission of advancing research 
into the role of culture, lifestyle, genetics, and genomics in health 
disparities.

                         GENETIC DISCRIMINATION

    The NHGRI has long been concerned about the impact of potential 
genetic discrimination on research and clinical practice, as a wealth 
of research has demonstrated that many Americans are concerned about 
the possible misuse of their genetic information by health insurers or 
employers. This concern has been a constant during my tenure as 
director of NHGRI, so it gives me great satisfaction that after a 13-
year legislative effort, the Genetic Information Nondiscrimination Act 
(GINA) has finally become law. When GINA takes effect in 2009, it will 
provide all Americans with solid protection against discrimination 
based on their genetic information in health insurance or employment 
circumstances. We hope that these protections will address the concerns 
that have thus far threatened the public's willingness to utilize 
genetic testing.

                         MEDICINE IN THE FUTURE

    Broad investment in innovative, large-scale, and adaptable models 
of research such as GWAS may accelerate the timeline for the 
development of advances in clinical options and thereby contribute to a 
decrease in the public health burden of many common diseases. With 
protections against discriminatory uses of genetic information in 
place, we anticipate that individual genome sequencing will become both 
commonplace and affordable, and that primary care physicians will 
routinely consult their patients' genome analyses for prediction of 
risk, diagnosis, and drug and dosage selections. If the public and the 
medical community are appropriately educated about both the 
significance and the limitations of genomic information, it may be 
possible to lessen the burden of disease through better screening and 
prevention programs, to minimize or avoid toxicities from drugs, and to 
select the right drug for the right patient, at the right time.
    Finally, as many of you know, next month I will step down as 
Director of the National Human Genome Research Institute, a position 
that has been my joy and privilege to hold for the past 15 years. Many 
historic opportunities lie ahead as genomics increasingly becomes a 
leading force in medicine, and I leave my position supremely confident 
that NHGRI and NIH will continue to achieve notable success in 
advancing the health of the American people. In closing, I would be 
remiss if I did not take this final opportunity to thank Senator Harkin 
and Senator Specter for their superb leadership on this committee and 
long-time dedication to the mission of the NIH. Your efforts, and that 
of your excellent staff, have been essential to the progress recently 
made in genomics research, and are very much appreciated.
                                 ______
                                 
               Prepared Statement of Dr. Anthony S. Fauci

    Mr. Chairman and members of the committee: I am pleased to present 
the President's budget request for the National Institute of Allergy 
and Infectious Diseases (NIAID) of the National Institutes of Health 
(NIH). The fiscal year 2009 budget of $4,568,778,000 includes an 
increase of $8,123,000 over the fiscal year 2008 appropriated level of 
$4,560,655,000.
    The mission of NIAID is to conduct and support research to 
understand, treat, and prevent infectious and immune-mediated diseases. 
The biomedical research that NIAID supports to combat diseases of 
worldwide concern, such as HIV/AIDS, tuberculosis, malaria, neglected 
tropical diseases, emerging and re-emerging infectious diseases, has 
taken on added importance in today's globalized society. As we address 
these problems in a global context, we naturally contribute to our 
country's preparedness against the threat of bioterrorism as well as 
naturally occurring disease outbreaks. In addition, we are advancing 
efforts to address other domestic health problems, such as HIV/AIDS, 
influenza, and asthma, allergy, and other immune-mediated diseases. 
Using a multidisciplinary approach that engages industrial, academic, 
governmental, and non-governmental partners, NIAID remains committed 
both to basic infectious and immune-mediated disease research and the 
application of this knowledge to the development of strategies to 
detect, prevent, and treat these diseases. This approach is emphasized 
in the recently updated NIAID strategic plan, NIAID: Planning for the 
21st Century--2008 Update.
    Looking forward, it is clear that the research activities of NIAID 
will become more important than ever, as current and as-yet 
unrecognized health threats will require new diagnostic, preventive, 
and therapeutic interventions. These new tools promise to have a great 
impact on public health over the next two decades.

             EMERGING INFECTIOUS DISEASES AND GLOBAL HEALTH

    Threats posed by infectious microbes do not remain static, but 
change over time as new microbes emerge and familiar ones re-emerge 
with new properties, such as drug resistance, or in new settings. Since 
2006, we have witnessed numerous examples of newly emerging and 
remerging infectious diseases outbreaks, including extensively drug 
resistant tuberculosis (XDR-TB), methicillin-resistant Staphylococcus 
aureus (MRSA), H5N1 avian influenza, Chikungunya fever, and dengue. We 
must anticipate that we will see more and more of these outbreaks in 
the coming decades. As economies and societies around the world have 
become increasingly interdependent, responding to emerging infectious 
diseases, as well as to long-established global health challenges such 
as neglected tropical diseases, has taken on a new urgency.
    Tuberculosis is an example of a re-emerging threat. The World 
Health Organization (WHO) estimates that in 2006, new cases of active 
tuberculosis (TB) worldwide exceeded 9 million and 1.7 million people 
died from TB. Antiquated and insensitive techniques for accurately 
diagnosing TB, complex and lengthy drug regimens and an increase in the 
prevalence of multi-drug resistant (MDR-) and XDR-TB continue to 
present major challenges to effective TB control. In 2007, the 
Institute released the NIAID Research Agenda: Multidrug-Resistant and 
Extensively Drug-Resistant Tuberculosis, which identifies research 
needs and priorities in several critical TB-related areas. The agenda 
also highlights the importance of fostering partnerships with public 
and private organizations to fuel the pipeline of available drugs, 
diagnostics, and preventive measures for TB.
    Malaria is an established infectious disease that continues to pose 
a significant global health burden. Malaria is becoming even more 
problematic with the emergence of drug-resistant malaria parasites and 
insecticide-resistant mosquito vectors. NIAID collaborations with 
public and private partners, including the Bill & Melinda Gates 
Foundation, build on the foundation of NIAID's robust malaria basic 
research program to foster the development of promising drug and 
vaccine candidates. Over the next two decades, we hope to have a major 
impact on the global TB and malaria burden through the development of 
vaccines that protect against these infectious killers. Our aim is 
excellent control of both TB and malaria through the use of vaccines 
and other interventions with the ultimate goal of eliminating malaria 
as a global disease threat.
    TB and malaria are not the only diseases emerging in drug-resistant 
forms. The Centers for Disease Control and Prevention estimated that in 
2005, more than 90,000 individuals in the United States developed 
invasive infections with methicillin-resistant Staphylococcus aureus 
(MRSA) and nearly 19,000 of these patients died. NIAID supports an 
extensive basic research portfolio on antimicrobial resistance, 
including studies of how bacteria develop and share resistance genes 
and the identification of new therapeutic targets. The Institute is 
partnering with industry, other Federal agencies, academia, and other 
organizations such as the Infectious Diseases Society of America, to 
identify research priorities, including clinical trials, to address 
this growing problem, and recently published a detailed research agenda 
on antimicrobial resistance in The Journal of Infectious Diseases.
    Seasonal influenza, which changes slightly every year, is the 
classic example of a re-emerging infectious disease. Influenza viruses 
also can undergo more drastic genetic changes that periodically enable 
them to evade pre-existing immunity and cause a pandemic, such as the 
deadly influenza pandemic in 1918 that killed more than 50 million 
people worldwide. NIAID supports a broad portfolio of research on 
influenza, including basic and applied research on the development of 
vaccines, diagnostics, and therapeutics against both seasonal and 
pandemic influenza. This foundation of research has underpinned the 
significant progress made in the development of new influenza 
interventions. For example, in 2007, based on clinical data from NIAID-
supported research, the FDA approved the first vaccine for humans 
against the H5N1 avian influenza virus. Further, NIAID-supported 
studies performed in collaboration with various industrial partners 
have demonstrated the extraordinary potential for a variety of other 
vaccine formulations and adjuvants to not only expand the number of 
doses of vaccine but also to broaden the vaccine's reactivity against 
various strains of influenza.
    As we look to how we might respond to unknown emerging and re-
emerging infectious disease threats in the future, it is apparent that 
the most practical approach may not always be the development of 
interventions such as diagnostics, vaccines, and therapeutics against 
just one microbe. Rather, the future of diagnostics will be rapid, 
accurate tools that can be used at the bedside or in the field in 
``real time'' to detect a wide variety of pathogens. We are working to 
develop vaccine platforms that can be easily adapted to different 
microbes by shuttling the genes for different antigens in and out and 
that can provide protection against a broader group of pathogens. 
Similarly, we are developing antimicrobial therapeutics that truly are 
``broad spectrum'' in their activity, both within and between classes 
of pathogens. Such antimicrobials could prove effective against drug-
resistant bacteria, including MRSA.

                           HIV/AIDS RESEARCH

    HIV/AIDS continues to exact a staggering toll. Although the Joint 
United Nations Programme on HIV/AIDS (UNAIDS) recently revised 
estimates to indicate a stabilization or decline in HIV infections and 
deaths in some parts of the world, the HIV/AIDS pandemic remains an 
enormous global health challenge. An estimated 33.2 million people 
worldwide are infected with HIV. In 2007, approximately 2.5 million 
people were newly infected with HIV, and 2.1 million died of AIDS.
    Despite the grim numbers, the Federal investment in HIV research 
has generated promising new results in the prevention and treatment of 
HIV/AIDS and in advancing our understanding of the virus and disease. 
An important example is the demonstration by NIAID-supported 
researchers that medically supervised adult male circumcision reduced 
by more than 50 percent the risk of heterosexual African men becoming 
infected with HIV. Our hope is that this and other advances in HIV 
prevention research will become part of a comprehensive HIV prevention 
``toolkit'' that will markedly decrease new infections over the next 
two decades.
    Perhaps the greatest success story in NIAID-funded AIDS research is 
that of therapeutics. NIAID-supported research helped make possible 
antiretroviral therapies that have transformed HIV from an almost 
uniformly fatal infection into a manageable chronic condition. Still, 
existing drugs are no longer sufficient for some HIV-infected patients 
because of the ability of the virus to develop resistance or because of 
the toxicities that can be associated with the therapies. Among the 
fruits of NIAID fundamental HIV research is the recent approval of 
three new potent and highly effective antiretroviral drugs: etravirine, 
maraviroc, and raltegravir. NIAID will continue to support the 
fundamental research that will be the foundation for future 
therapeutics that will be even more user-friendly and inexpensive, 
making universal access to therapy more feasible over the next two 
decades.
    Prevention efforts continue to be a major component of the HIV 
research program of NIAID, and the most powerful prevention tool would 
be a safe and effective HIV vaccine. The development of an HIV vaccine 
remains one of our greatest scientific priorities, but also one of our 
greatest scientific challenges. The pathway to a vaccine is being 
elucidated through the fundamental basic research that remains the 
foundation of NIAID. For example, researchers at the NIAID Vaccine 
Research Center and their collaborators determined the atomic 
structures of a neutralizing antibody and the conserved area of the HIV 
surface protein (gp120) to which the neutralizing antibody binds. This 
binding site is the same site that the virus uses to bind to cells of 
the immune system. Such studies are helping us to identify components 
of HIV that may serve as targets for future vaccine candidates and may 
bring us closer to a safe and effective HIV vaccine.

                          BIODEFENSE RESEARCH

    Since the beginning of the acceleration of our biodefense research 
program in fiscal year 2003, NIAID has achieved a number of successes 
in the development of countermeasures against significant bioterrorism 
threats; these countermeasures are either in the Strategic National 
Stockpile or available for use in an emergency. Promising candidate 
countermeasures in development include ST-246, a smallpox drug 
candidate that has protected both rodents and nonhuman primates from an 
otherwise lethal exposure to live poxviruses. The FDA has granted 
orphan drug status to ST-246 and awarded the compound fast-track status 
which will expedite its regulatory review. The vaccine platforms, rapid 
diagnostics, and broad spectrum antimicrobial therapeutics that we aim 
to develop for emerging infectious diseases over the next two decades 
will also be directly applicable to our biodefense research program.
    In addition, and as important, NIAID has developed a physical and 
intellectual research infrastructure that has been critical to our 
ability to respond to new and re-emerging infectious diseases. Without 
this expanded infrastructure, the biomedical research response to the 
emergence of infectious disease threats such as H5N1 avian influenza, 
MRSA, and XDR-TB would not have been as rapid.

                  RESEARCH ON IMMUNE-MEDIATED DISEASES

    Autoimmune diseases, allergic diseases, asthma, rejection of 
transplanted organs, and other immune-mediated disorders are 
significant causes of chronic disease and disability in the United 
States and throughout the world. NIAID-supported research in immune-
mediated diseases has led to significant advances in our understanding 
of the mechanisms underlying these diseases and in the development of 
strategies to detect, prevent, and treat them.
    Food allergies continue to be a growing concern and an emerging 
focus of public attention. NIAID remains committed to basic research to 
advance the understanding of food allergy and food allergy-associated 
anaphylaxis. To bring new investigators and novel ideas into food 
allergy research, NIAID is supporting a new initiative, Exploratory 
Investigations in Food Allergy, in collaboration with public and 
private partners. NIAID also is expanding support for clinical trials 
in food allergy, with ongoing trials to prevent the development of 
allergies to particular foods, such as peanut, and to reverse 
established allergy to milk, eggs, and peanut.
    The Institute also supports research to improve outcomes for 
transplant recipients, with establishment of immune tolerance as a 
major priority in this area. The NIAID Immune Tolerance Network is 
making steady progress toward the long-term goal of reducing the need 
for costly and potentially risky immunosuppressive drugs that are the 
current standard treatment to prevent transplant rejection. A total of 
11 kidney and liver transplant recipients are no longer on 
immunosuppressive drugs, some for as long as 4 years. We hope that 
eventually a substantial proportion of organ transplant recipients will 
not require immunosuppressive drugs.
    The establishment of immune tolerance is a goal not only for 
transplantation, but also for other immune-mediated disorders, such as 
allergies. We look forward to the use of tolerance to have a major 
impact on allergies, including food allergies, and other immune-
mediated disorders in the coming decades.

                               CONCLUSION

    For more than six decades, NIAID has conducted and supported basic 
research on infectious and immune-mediated diseases that has 
underpinned the development of vaccines, therapeutics, and diagnostics. 
These, in turn, have improved health and saved millions of lives in the 
United States and around the world. Through partnerships with 
industrial, academic, governmental, and non-governmental partners, the 
Institute will continue to leverage these fundamental discoveries into 
the tools needed to achieve a healthy world.

    Senator Harkin. Dr. Zerhouni, thank you very much, that was 
really eloquent and elegant, and I appreciate that very much. I 
just wondered if--Senator Cochran has joined us, did you have a 
statement you'd want to make, Senator Cochran?
    Senator Cochran. Mr. Chairman, thank you very much, I do 
have a statement that I would ask be included in the 
appropriate place in the record.
    Senator Harkin. Sure, without objection.
    Senator Cochran. Thank you.
    [The statement follows:]

               Prepared Statement of Senator Thad Cochran

    Dr. Zerhouni, thank you for joining us today to discuss the fiscal 
year 2009 budget for the National Institutes of Health. We appreciate 
your efforts to improve the health of Americans through medical 
research aimed at the prevention and treatment of diseases. I am 
pleased that the Committee has provided an increase of over $1 billion 
above last year's level and I look forward to your comments on the 
agency's vision and plan for these additional resources. I would also 
like to welcome our distinguished panel of scientists. The insight you 
will share today of your experience with the NIH and its research will 
be helpful to the work of this committee.
    The research at NIH addresses the pressing health concerns in our 
country and it is important not only to complete this research, but to 
translate it into new therapies and better outcomes for patients. This 
Committee will continue to encourage you all to do this.
    I appreciate the challenges you are facing and your hard work. I am 
interested in helping the NIH succeed in these very important efforts.

                              NIH FUNDING

    Senator Harkin. For the record, accompanying Dr. Zerhouni 
today is, of course, Dr. Francis Collins whom I spoke about in 
my opening statement, the Director of the National Human Genome 
Research Institute and Dr. Anthony Fauci, Director of the 
National Institute of Allergy and Infectious Diseases, who's 
been at NIH since--is that right, since 1968, Tony? Wow.
    Dr. Elizabeth G. Nabel is the Director of the National 
Heart, Lung, and Blood Institute, appointed to that position in 
2005, I think, from Dr. Lenfant, if I'm not mistaken, who was 
there for many years.
    Dr. John Niederhuber is the Director of the National Cancer 
Institute.
    We thank you all for being here today.
    Well, Dr. Zerhouni, just picking up on that, as I said, 
that very elegant presentation, we think about where we've 
been, and we're on the cusp of some of these new things, we 
have to follow these leads. Tell us what that would mean in 
terms of budgetary implications. In other words, we've got a 
lot of things we've got to be looking at--I assume this spreads 
across every Institute, in terms of following these leads. But, 
what should we be thinking about in terms of the growth in NIH 
funding? As I said, Senator Specter and I are going to try to 
introduce a bill to try and get that money back up again, we're 
facing some pretty tough budget times right now--what should we 
be thinking about in terms of the funding for NIH next year? 
The year after, the year after, perhaps, in order to adequately 
follow these leads?
    Dr. Zerhouni. There are many ways to answer this question, 
but I'll give you some parameters I've learned are critical.
    You can not sustain an enterprise where you have to have 
people commit their lives, their careers--it takes 15 years, 
sometimes, to just make an impact when you're following the 
lead, this is not automatic. So, these individuals need to have 
some certainty that the budgets will be there to sustain them 
in their effort, so predictability in the budget is very 
important.

                              SUCCESS RATE

    The second is that, you have to have a reasonable success 
rate. When you tell a young individual, ``You will come in, you 
will come in at age 30, 32, having spent 20 years of your life 
training yourself, and then you're going to make $40,000 for 
the next 10 years, and maybe at the end, if you're very, very 
good, you might get a grant from the NIH with a 17 percent 
success rate. How does that sound to you?''
    Without a 30 percent success rate, on average, we've notice 
that, fundamentally, our ability to maintain the competitive 
nature of science, and the ability to explore the avenues--not 
knowing, really, where the next breakthrough is going to come 
from. People forget that science is not an engineering task, we 
don't know all of the answers, we have to seek them. We've done 
this for 50 years. People forget that the history of true 
modern research in medicine is only 50 years old. So, we are 
early in that stage. Losing momentum is very critical.
    So, a reasonable success rate, a predictable funding, and 
funding that does not decrease in real terms--which is what we 
have had to deal with, which forces you to make priority 
choices, not knowing, really, where the breakthrough will come 
from. Because, in science, as we've noted, sometimes somebody 
is doing something completely unrelated, and all of a sudden, 
that something becomes a cure in cancer, or that thing in 
cancer becomes a cure in AIDS. We've seen that over and over 
again.
    So, what is key is to maintain your capacity over time, 
make sure that new, young investigators are encouraged to enter 
the career, and make sure that we are not dealing with a very 
erratic process. Medical research is a long-term process, it's 
not something you can manage every 12 months. You have to 
commit.
    But we have a plan, we have a strategy. This strategy is 
known the world over. If we're not following these leads, I can 
assure you, somebody will. That won't be us.

                           NEW INVESTIGATORS

    Senator Harkin. Dr. Zerhouni, you have the NIH Director's 
New Innovator Awards that you have in your office that we 
provided some money last year for that, $56 million, that goes 
to new investigators. We included $108 million for the program 
in our next bill--will that be enough to support the New 
Investigators Award System? Is this part of bringing, getting 
these new people in, and getting them started?
    Dr. Zerhouni. Right, so this is a stop-gap that we have to 
use, because what my main concern is--and my colleagues know 
that--is that if you do the projections, and if you don't fund 
enough scientists today, you won't have them 10, 15 years from 
now.
    So, what we've done--with a lot of hardship--is to shift 
money into young investigators, new investigators. This needs 
to continue.
    New Innovators was addressing two goals: one is that, once 
success rates go down, people become very conservative. They 
don't take chances, they don't take risk into new areas of 
research, they want to be sure. So, we wanted to encourage 
risk-taking, and encourage new entrants to come in--that's what 
the New Innovators Awards do.
    Our data shows that we really need to fund something around 
3,000 new scientists a year to enter NIH. Right now we're below 
that number, and ideally that would be the goal that we have to 
have--no matter what the budget does--we need to encourage 
risk-taking, new ideas, innovation, and new investigators.

                    FUTURE OF HUMAN GENOME RESEARCH

    Senator Harkin. Thank you, Dr. Zerhouni.
    I have questions for all of the panelists, I just have one 
more question and then I will yield to my colleagues that are 
here.
    Dr. Collins, obviously the presentation this morning that 
Dr. Zerhouni made is right up your alley. I guess what I'd like 
to ask you about is again, talk about the future. We've mapped 
and sequenced the genome, we've now made all these discoveries 
in terms of the clues--where we do go from here with the Human 
Genome Project or with the Human Genome Institute? Where do we 
go from here with that? Tell me about the 1000 Genomes Project, 
and what that might mean? Are you supportive of that, is that 
something that we should be looking at, and trying to support, 
the 1,000 people that they want to do that on?
    Dr. Collins. Thank you, Senator. It is my last appearance, 
officially, as a Government employee in front of this 
committee, and I would like to express my sincere thanks to 
you, and to Senator Specter, and to the whole subcommittee for 
their consistent support and interest in what NIH is doing.
    I certainly remember when I first came here 15 years ago, 
there was a lot of skepticism about whether the Human Genome 
Project had any chance of succeeding, and it was your support, 
and that of others Members of the Congress, that saw us through 
some challenging times, where the technology had to be 
invented, and people had to be recruited, and a lot of 
milestones had to be achieved, and the celebration of the 
accomplishment of those goals in April 2003 is very much a 
testimony to this Congress and to their vision for supporting 
this.
    Personally, I want to say thank you to you, for all the 
wonderful conversations we've had through the years about this.
    It is a glorious time in genome research, as Dr. Zerhouni's 
testimony indicated. I've just counted up the number of 
projects that my Institute is currently managing, going--
building on the foundation of having the human genome 
sequence--there are 19 of them. These are all focused on 
specific ways in which we can learn from that instruction book, 
how it operates, and how glitches in the instruction book, our 
genome, can lead to health or disease.
    We are learning a prodigious amount every day. I can tell 
you, however, that none of those 19 projects are going as 
rapidly as they could--we are constrained, and not by talent, 
not by ideas, not by opportunities, but very much by the 
budgetary abilities that we have to expand on these projects. 
That is, of course, for me a source of some frustration.
    The 1000 Genomes Project is one of those--this is an 
international effort, just as many of the genome projects have 
been. It's rather amazing to be able to say that the people 
were skeptical about whether we'd ever sequence one genome, 
we're now proposing to sequence 1,000 of those, derived from 
DNA samples from individuals in Europe, and Asia, and Africa, 
and to have that done in the next 2\1/2\ years.
    We're doing this in collaboration with England and China, 
and we're already deep into a pilot project which in its first 
3 months of effort generated more DNA sequence data than has 
ever been generated in the history of the planet, so we're 
really producing a vast amount of interesting information 
that's laying out this catalog of human variation at a level of 
detail not previously imagined possible.
    It's going to teach us a lot about how it is that DNA 
variation plays a role, and who's at risk for what, and that's 
just one of these 19 projects.
    There more that we could be doing, if you'll give me just a 
moment, I'd like to mention two.

                         GENES AND ENVIRONMENT

    One of the things we really need to understand more about, 
of course, is how the genetic risk factors interact with the 
environment.
    All of those banners on the diagram that Dr. Zerhouni 
showed--which are enormously exciting advances, figuring out 
risk factors for diabetes and heart disease and cancer and 
asthma--those are, of course, inherited risk factors that 
you're not going to be able to change in the people who have 
them. But it is an interaction between those genetic risks and 
environmental exposures, such as diet, and lifestyle and 
medical surveillance and whatever's in the air and the water, 
that determines whether somebody is going to get sick, or not. 
We could modify those things, if we understood exactly who's at 
risk, and we could focus on that, in an individualized way. 
That's what personalized medicine is all about.
    But, collecting that data is not trivial. A dream that I've 
had for the last 4 years, but haven't been able to get off the 
ground in the current budget climate, is to have a national 
study of health and disease, collecting information on, 
perhaps, half a million volunteers from across the country, who 
would basically agree to have their environmental exposures 
studied, as well as their medical conditions, and their DNA. If 
we put that all together, in an organized effort with access to 
qualified investigators, we would finally, really have a 
rigorous way of understanding this.
    You could call this the American Genes and Environment 
Study, or AGES, some of us have done that. We've organized a 
group of more than 60 scientists to think about how to put this 
together. I have yet to meet somebody who doesn't think this 
would be an enormously exciting project to undertake, but it's 
expensive. It's genome project-like in its budget, and at the 
present time it's been hard to get it off the ground.

                      RARE AND NEGLECTED DISEASES

    That's one. Another one, which I'm enormously excited and 
optimistic about, is to take the discoveries that we are making 
about the causes of where neglected diseases, where we are 
making great progress and really, in a very intentional way, 
translate those into treatments.
    The NIH has made major investments, particularly through 
the Roadmap that Dr. Zerhouni has so effectively championed, to 
put us in the position to do that, and we have many other 
pieces in place, to take a discovery about a rare disease, and 
lead it all the way to a clinical trial. In a circumstance 
where the private sector, understandably, is not going to be 
very interested in investing, because the market size is going 
to be quite small. We are only missing on, sort of, major piece 
here, and an initiative to fill in what's called the Valley of 
Death, between when you have a promising lead compound, and 
when you have something you could actually contemplate putting 
into a patient is something I would be enormously excited 
about.
    We couldn't have really done that 4 or 5 years ago, but we 
could now. With an infusion of just the right amount of 
support, I think this is something that we've underlined what 
we're really about at NIH, which is trying to find cures. Yes, 
we do great basic science, and we're proud of that, but our 
goal--as yours--is to take that to the clinic, and do something 
for patients.

                          BUDGETARY CHALLENGES

    So, I'm excited about all of those things, but again, being 
my final hearing, I guess I could speak about as bluntly as 
anybody at the table--I am very concerned about whether we will 
achieve those kinds of optimistic outcomes, if we can't turn 
the corner on what has been a very difficult 5 years.
    It's been my most difficult 5 years, having to turn away 
young investigators--some of whom have gone away and won't come 
back--they've given up. Having seen the way which science that 
could have gone forward, has been blunted by the inopportunity 
to jump in and provide those kinds of supports. Having seen a 
delay in the health benefits that we are all dedicated to 
achieving, being slowed down by the inability to push forward 
agendas which, scientifically, are very exciting, but we just 
can't do it with the current support.
    Frankly--as we're also worried about our economic 
circumstances, seeing how an investment by NIH which various 
studies have indicated, pays back somewhere between two and 
seven-fold--isn't happening, either out there in our country, 
which is where most of our money goes.
    Frankly also, as somebody who's worked in the international 
community, as I've had the pleasure of doing, I'm seeing our 
leadership on many of these projects eroded by the fact that 
NIH is not keeping up with what's happening in other countries, 
including England, and China, and India and that can't be a 
good thing for our country.
    So, I appreciate what you and Senator Specter are doing in 
this hearing, to highlight the importance of maintaining that 
kind of support, and perhaps, catching up from what has been a 
pretty difficult half a decade. If we could turn that corner, 
keep our investigators who are just on the edge of giving up, 
inspired that they could actually make a contribution, then I 
think we could recover a lot of what we're in danger of losing.
    Thank you for the extra minutes you gave me to answer that 
question.
    Senator Harkin. Dr. Collins, thank you very much. Again, 
for the benefit of members of the subcommittee and perhaps some 
of the public who may not know these figures, when Dr. Collins 
took over the Human Genome Project in 1993, I can remember the 
hearings at that time when I was Chair at that time, and the 
estimate was that it would take us 15 years, and over $3 
billion to map and sequence the human genome. But we did it in 
10 years, basically--there's a few little holes that were left 
over--but basically 10 years, and less than about $2.6, $2.7 
billion.
    Now, that's important, but there's one other thing that's 
very important, that I think members ought to know. That it was 
about that time, about right around 1993, 1994, when there were 
moves made to take this from the public sector and put it in 
the private sector. That the Human Genome Project would better 
be done in the private sector, rather than the public sector. 
There was quite a battle about that at that time, and I can 
remember, people said, ``Why should we be investing, why should 
we be investing public money in this when the private sector 
can do it?''
    Dr. Collins was very eloquent at that time, and very 
forceful, in telling us that, no, this belongs in the public 
sector. This basic research ought to be available to everyone, 
and if it's in the private sector, of course, there would be 
patents and holds and all kinds of things on some of the basic 
research, and that's not where it should be held.
    So, again, Dr. Collins, we owe you a great debt in being so 
forceful at that time and convincing us that this should remain 
in the public sector, because right now, because of this--a 
researcher anywhere in the world can get data from the Human 
Genome Project and further that research on.
    To me, this again is a legacy that is almost incomparable 
in some ways. I think that the fact that we kept this in the 
public sector, again, is going to serve us well, not today but 
also in the future just making sure that everyone has access to 
it, and no one has to pay a single dime to get that 
information.
    So, with that, again, Dr. Collins, thank you for your great 
service in that regard. I would yield now, to Senator Specter, 
of course, who just came back.

                          COST TO CURE CANCER

    Senator Specter. Well, thank you, Mr. Chairman.
    I've been dealing with you, Dr. Niederhuber on the cancer 
issue. President Nixon made his famous declaration in 1970 on a 
war against cancer, and I do believe that had that war been 
pursued with the same intensity as other wars, many of us 
wouldn't have contracted cancer.
    We've asked for a projection as to what it would cost to 
``cure'' cancer, and I put cure in quotation marks, because 
absolutes are understandably impossible, but were we to make a 
major frontal assault, and you come back with a figure of $335 
billion over the next 15 years.
    What are the realities as to how far we can go on attaining 
the goal of a cure? We know that there are many, many strains. 
There's been an enormous amount of research, there's been an 
enormous amount of progress. Talking to Senator Lindsay Graham 
about his mother who had Hodgkin's years ago--very, very 
different world from the really complex regimen that I had--am 
having, really--on chemotherapy. So, what is the reality? How 
close could he have come to a ``cure''?
    Dr. Niederhuber. Senator, you always ask the tough 
question.
    First of all, I'd like to say a word of congratulations to 
you for finishing your 12th cycle of chemotherapy. I suspect no 
one in the room knows, perhaps, better than I do, how difficult 
it is to go through these cycles of chemotherapy.
    So, you're to be congratulated.
    Senator Specter. Thank you.
    Dr. Niederhuber. I talked to a friend of ours at the 
University of Pennsylvania just a couple of days ago, and he 
also lauds how you've been able to do this, and do it without 
missing a minute of work. So, you're to be congratulated.
    Cancer is, as you mentioned, is many, many diseases. Maybe 
more than 1,000 diseases. As we get to understand the genetic 
differences--the genetic differences in breast cancer, the 
genetic differences in colon cancer--and how those genetic 
differences, as Dr. Zerhouni so eloquently pointed out, affect 
a network within the cell. How those cells interact--not just 
within the cancer, but how those cells interact with the so-
called normal cells in which that cancer lives. It's a very 
complex, and very dynamic process.
    I can't tell you how many years it will take to cure, or to 
make this disease much more of a chronic set of diseases that 
we can live with, that we can prevent--that's obviously our 
goal--that we can understand who's at risk from the genetic 
kinds of analysis that we can do on individuals, and can take 
measures.
    Senator Specter. Well, how far will $335 billion take us 
over 15 years?
    Dr. Niederhuber. I think it will take us a long way.
    Senator Specter. Because if you can quantify it, in some 
way, I think this subcommittee can take the lead in finding you 
the money, somehow.
    Dr. Niederhuber. What I did when I understood your asking 
that question and seeking advice from some of the communities, 
the cancer communities, the different organizations in the 
country, who also then came to me and asked for my opinion on 
this was to put together a team at NCI to think strategically 
about the various investments we're currently making, and what 
the opportunities for expanding those investments would be in 
the future.
    We've, I think, prepared--or are in the process of 
preparing--what might be considered, I believe, a realistic, 
but well-thought out, and I would say, forward-looking business 
plan for the future. I'd be happy to----
    Senator Specter. You've given us a timetable of 15 years, 
and you've given us a figure, $335 billion. I've only got 8 
seconds left, although once the light goes on, you can still 
talk.
    Senator Harkin. Take more time.
    Senator Specter. I haven't gotten to the question yet--
where are we, how close to a cure?
    Dr. Niederhuber. I know it's a very difficult question and 
I'm not sure that I can give you a figure. We've felt that if 
we could add to the NCI budget $2 billion a year, each year for 
the next 5 years, that that would go a long way toward helping 
us build capacity within our country, in terms of attracting 
young people, attracting disciplines that haven't previously 
worked on cancer, to work on cancer.
    I just attended a meeting that I sponsored, Monday and 
Tuesday, at which we brought together physicists, 
mathematicians, individuals who work on evolutionary biology--
individuals who haven't worked in the field of cancer before. 
We had a 2-day meeting to brainstorm how these individuals 
might bring a different set of eyes, if you will, and a 
different set of thinking toward the magnitude of the problem 
that we face in cancer.
    It was a very exciting meeting. I learned a lot from 
listening to those individuals, I think, that will greatly 
shape the future.
    But, I think one of the things that came out of that 
meeting, Senator, was again what Dr. Collins said--that we, as 
a country, need to significantly invest in bringing bright, 
young people into the biological sciences, especially into 
cancer, and to create a capacity for us to be able to invest 
the resources of our country in this science. If we don't build 
that infrastructure and build that capacity, then it doesn't 
make any difference how much money we have. We have to have 
bright young people, we have to have people to work on the 
problem.
    So, the first challenge, I think, for us at NCI is to 
increase our investment in attracting people to work on this 
particular problem.
    I also think that we have a very real need to invest in 
retooling or re-engineering our clinical trial infrastructure. 
If we're going to take the steps forward that Dr. Collins has 
so eloquently talked about, and do drug discovery, and highly 
personalized characterization of each patient and their cancer, 
and match that with solutions of treatment, that's going to 
require different clinical trial structure than we currently 
have.
    We worked, on July 1 and 2, with the National Institute of 
Medicine, at a 2-day symposium to talk about these issues about 
re-engineering the clinical trial structure. Again, that will 
take a significant amount of investment, financial investment, 
in order to retool that, re-engineer that, so that we can work 
effectively in the new era.
    Senator Specter. Well, I won't ask another question, 
because others are waiting to question. But, when you talk 
about attracting the scientists, working with $335 billion, you 
can attract scientists. You talk about retooling clinical 
science, clinical tests, $335 billion will allow you to retool.
    I know the questions are difficult, perhaps impossible, but 
we need to have, you know, the best professional judgment, 
because to sell that kind of money to the Congress is going to 
require something that we can put our hands around. When you 
get into the appropriations room, you have to have something 
more specific to pull out those big dollars.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Specter.
    Senator Durbin.

                   NIH FUNDING AND SETTING PRIORITIES

    Senator Durbin. Thank you very much.
    I want to just show a chart here, if I can, which is 
probably familiar to you, it may have been produced by some of 
you, and it shows the actual appropriations on the yellow bars, 
since fiscal year 2003 through fiscal year 2009 and the 
purchasing power at NIH that came from those appropriations.
    It shows two things--first, that the amount that has been 
appropriated by Congress has not kept up with the inflation 
that you face, and so the actual amount available for medical 
research and all of your other endeavors has actually declined 
during these years.
    The second point it makes is the administration and 
Congress made conscious decisions during this period of time to 
initiate a war that costs $15 billion a month, and to give tax 
cuts to the wealthiest people in America, so there were fewer 
dollars available for domestic discretionary spending, as a 
result of those two major policy decisions.
    In that backdrop, I'd like to ask you to address one 
general question. I have a chart here--you're undoubtedly 
familiar with it, which shows the funding at each Institute at 
the National Institute of Health during this same period of 
time, and in fact, it goes back a little further in time, to 
1998.
    Until 2003, the amount of money to each one of the 
Institutes that you're in charge of was growing, and this was 
because of the commitment to double the medical research, and 
then comes that year--as evidenced on the other chart, it 
started to flatten out, and decline, and that shows the way 
that that's headed.
    My question is fairly general--I started by saying that 
it's not uncommon for Members of the Senate to be visited by 
people from our States who have members of their family who are 
suffering from a disease--a wide spectrum of diseases. Without 
fail, they all ask us for more funding for medical research for 
the disease that affects someone they love.
    They all argue that not enough money is going to that 
research, that field of research. I kind of took the position 
long ago--rightly or wrongly--I couldn't decide, I'm a liberal 
arts lawyer, what do I know about where the money ought to go? 
I said, I'm just going to give the NIH as much money as I can 
in the aggregate, and I hope they'll make the right decision.
    It turns out that was a probably incorrect, if not 
simplistic answer. We do fund the Institutes. We really, kind 
of, decide at the congressional level, how much money will go 
to each Institute. There are winners and losers in that 
process.
    So, when the family with a child--an autistic child--comes 
to see me, and says, ``You're not spending enough money on 
autism. Don't you know, Senator, that 1 out of every 150 kids 
in America has this disorder?''
    In my State, in the last 10 years, there's been a 353 
percent increase in the diagnosis of autism, and of course, the 
costs are unimaginable for these children, and their care 
throughout their entire lives.
    So, my first question--fairly simple question--but maybe 
not easy to answer. If we gave you $30 billion, and didn't have 
any strings attached, what would be the difference in this 
chart? Do we make choices--political choices--on Institutes, 
which you as researchers and doctors, step back from and say, 
``That isn't where I'd spend the money.''
    Dr. Zerhouni. This is a great question, this is a question 
I face all the time, personally. I know, over the past 5 years, 
I can tell you, there's no tears left in my lachrymal glands 
about how you make those decisions.
    That's the important question, but it's not true that all 
of the money, when it doubled, went into the same things 
without any change or any decisions. Actually, if you look at 
the topics that NIH has, over a period of 10 years, for 
example, 50 percent of the efforts that we make in any one 
area, turn over in about 8 years.

                                GENOMICS

    So, although NIH, you have a $30 billion budget, and you 
see these budgets, what's underneath these curves, is very 
different. For example, if you look at the efforts that are 
done in genomics, those didn't exist 10 years ago across all of 
the Institutes. Every single Institute here, I will tell you, 
spent 5, 10 percent of its dollars on these genomic studies, 
which were not done 10 years ago. Bio-computing--if you look at 
their basis--are available for bio-computing, for doing 
research on every disease--autism included, or any other 
diseases, these were not there 10 years ago.
    We just developed, for example, through Roadmap, a Chemical 
Genomics Center. That center, that Dr. Francis Collins 
reflected about, can perform, in 2 days, 1.5 million tests. 
This is the equivalent of what it would have taken a scientific 
group to do in 15 years.
    So, there are things that you change, the process that you 
have to really engage into is an open, transparent, portfolio 
analysis process, which we do.
    Senator Durbin. I'm running out of time. Maybe it will take 
you a moment, maybe you can't answer this. But, if we gave you 
$30 billion, with no strings attached, would this look the 
same?
    Dr. Zerhouni. No, absolutely not. It never looks the same, 
from year to year--even between 2003 and today.

                              NIH FUNDING

    Senator Durbin. My point is, are we pushing allocating, 
politically, on our end of it, research into areas that you 
think are not the best expenditure of limited tax dollars?
    Dr. Zerhouni. I would say that this is not an issue, in the 
aggregate. Frankly, Congress expresses priorities, we have an 
independent peer-review process which we absolutely cherish, 
because it is the process by which we go into scientific 
opportunity.
    So, I think what is important, however, is that without the 
dollars, you tend to have to make choices that sustain what you 
have, and do not allow you to be as risk-taking as you would, 
otherwise.

                            DISEASE FUNDING

    Senator Durbin. Mr. Chairman, can I ask one last question?
    Senator Harkin. Sure.
    Senator Durbin. Would you address this issue of autism? I 
know there have been so many theories----
    Dr. Zerhouni. Right.
    Senator Durbin. The parents that come see us share 
compelling stories about what they're dealing with, and arguing 
that we're not putting in the adequate money into research into 
this disease.
    Dr. Zerhouni. Autism is one of the most important and 
greatest concerns that I have, as well as my colleagues, in 
particular, National Institute of Mental Health, Dr. Insel.
    As you know, we have put an Inter-agency Committee on 
Autism, that is coming up with a strategic plan--that is how 
we're going to drive, essentially, the investments in autism, 
we're funding more centers; you just heard about a study that 
came out last week about the first really important discoveries 
in terms of the genetics of autism. I think it's advancing, 
it's progressing.
    Could I use twice the money? Absolutely, I could. But I 
have other competing priorities, too.
    Senator Durbin. Thanks, Mr. Chairman.
    Senator Harkin. Thank you.
    Senator Murray.

                         TRAUMATIC BRAIN INJURY

    Senator Murray. Well, thank you very much, Mr. Chairman, 
and thank you for an excellent presentation. I really 
appreciate the tremendous work that all of you do.
    You focused a lot on diseases--one of the, kind of the 
other side of the picture that I've been looking at as a member 
of the Veterans' Committee and working with returning soldiers 
on traumatic brain injuries and post-traumatic stress syndrome, 
and the growing number of men and women that are dealing with 
that, and the broader picture across America of neurological 
disease and disorders, and injuries and was surprised to learn 
that nearly 100 million Americans are affected by that, and the 
huge impact on people's health and our economy--I think it's $1 
trillion that's being spent on neurological illnesses, the 
long-term impacts of that. Can you talk to me a little bit 
about what NIH is doing in a coordinated neurotechnology 
research, and what we can expect?
    Dr. Zerhouni. In terms of traumatic brain injuries, we have 
really increased our investment--it's about $87 million a year 
now, as compared to a few million just a few years ago, 
primarily because of the issues--fundamental issues, related to 
our understanding of traumatic brain injury in the context of 
conflict, and the Iraq war, in particular.
    In terms of injuries, generally, when you look at all sorts 
of injuries, we spend about $17 million, understanding musculo-
scalpal injury, and all types of injuries. However, at this 
moment, this is not the only focus we have.
    In collaboration with the Department of Defense, we have 
mounted an initiative in trying to understand both traumatic 
injury at the fundamental level, and post-traumatic stress 
disorder.
    Now, when you really look at the impact of post-traumatic 
stress disorder and our understanding of it, you realize that 
this is going to require a response that is not just affecting 
the individual that is affected by PTSD, but the family around 
the individual, the community around the individual, and we do 
have to have a proactive response, because there are 1.7 
million service members that have served in Iraq, and about 15 
percent of those suffer from PTSD, a major public health issue, 
that will require full spectrum.
    We do the research; we're collaborating with the Armed 
Services today on a $70 million joint project to create, in 
fact, the ability to diagnose PTSD very reliably. Then, with 
the Department of Defense, we're working on a project that will 
create community centers, so that we can, in fact, detect and 
manage that on the ground.
    Senator Murray. So, we can expect to see a coordinated, 
solid look at this?
    Dr. Zerhouni. Actually, you know, it's interesting--we have 
never been more coordinated than on this issue, across 
agencies, including DOD, VA, NIH, CDC, all of us.

                       PANCREATIC CANCER RESEARCH

    Senator Murray. Fantastic. Thank you, I appreciate that.
    On another question, Senator Durbin mentioned we have 
constituents who come to us--one of the groups that I'm hearing 
a lot from is the pancreatic cancer groups, they are very 
concerned. They know that NCI developed, I think it was 39 
recommendations for pancreatic research back in 2001, and only 
5 of those are being implemented. Can someone give me an update 
on where we are with pancreatic research? There's a growing 
trend of that.
    Dr. Niederhuber. Well, we're continuing to increase our 
incentives to the research community but trying to write 
specific RFA grant applications or opportunities. We continue 
to support, through the SPORE program, our Specialized Program 
of Research Excellence, which is focused on translational 
research.
    So, I think we can continue to put resources on the table 
and ask for applications due to increased interest.
    The second, and probably more stimulatory work is our whole 
genome scanning. We are actually looking at pancreas, in large 
cohorts, and one of the organ sites to try to determine, if we 
can, what regions in the genome might predict risk for 
developing pancreatic cancer.
    Senator Murray. So, there's a lot of potential at that 
point?
    Dr. Niederhuber. So, there's a lot of potential to inform 
that. We hope, too, that the TCGA pilot project will eventually 
get expanded to other tumors--pancreas would certainly one of 
those that we'd be very, very interested in doing, as that 
pilot project is proving very successful.

            HIV/AIDS VACCINE TRIALS NETWORK LIABILITY ISSUES

    Senator Murray. Thank you very much, I appreciate that.
    Dr. Fauci, while you're in front of me, as you well know, 
Fred Hutchinson Cancer Research Center in my home State is 
working with the NIH to administer the HIV/AIDS vaccine trials 
network, and it's inherently a Government function, they are 
doing the research on it, and they're very concerned about 
being sued for damages, and the issue of liability is really 
threatening them. Can you tell me, is there any update on that?
    Dr. Fauci. We've been working very closely with the 
officials, at the Institute, at the University of Washington, 
particularly at the Fred Hutchinson Cancer Research Center (the 
Hutch), because as you know--and for those who are not aware of 
it--the data center for our vast vaccine trials network is 
centered at the Hutch, with Dr. Lawrence Corey being the 
principal investigator.
    The issue is the concern that of, in fact, there is a suit 
against an adverse event that might occur somewhere far distant 
to the Hutch, what would that mean with regard to the liability 
and the vulnerability of the Institution for being funded? So, 
we're working very closely with the officials from the Hutch, 
together with members of the Department of Health and Human 
Services to figure out if we can evoke some of the existing 
authorities to help cover.
    The idea of insurance itself--they have plenty of insurance 
there, but they're afraid that if it's a massive suit, that 
they would not be able to cover that. So, we really--
literally--on a weekly and monthly basis, are trying to work 
something. I know officials have met with me, with people from 
Dr. Zerhouni's office, and himself, as well as with people at 
the Department of Health and Human Services, Secretary Levitt's 
staff--so we're actively on that. I do hope, and feel 
optimistic that we'll come to some sort of resolution, so that 
we can continue without the anxiety of liability.
    Senator Murray. I really--this is really incredibly 
important research that they're doing, I would hate to see it 
halted or slowed down as a result of the liability issues.
    Dr. Fauci. We agree with you completely, Senator.
    Senator Murray. Okay, thank you very much. I appreciate it.
    Thank you, Mr. Chairman.
    Senator Harkin. Thank you, Senator Murray.
    Senator Cochran.

                           OBESITY CHALLENGES

    Senator Cochran. Mr. Chairman, thank you very much.
    Dr. Nabel, I'm advised that since the early 1990s, the 
obesity rate has increased by 33 percent, resulting in serious 
health consequences for over 60 million people.
    Ten years ago, there were guidelines that NIH issues, 
regarding overweight and obese challenges, and physicians have 
been relying on those guidelines for 10 years. Is it time that 
we updated the guidelines? Or does your Institute, or others, 
have specific plans to deal with the challenges that this 
problem presents?
    Dr. Nabel. Senator Cochran, that's an excellent question 
and you importantly highlight the grave importance of 
overweight and obesity in our country, particularly among young 
people, and we're very, very concerned.
    The answer is yes--we're in the process right now, the 
National Heart, Lung, and Blood Institute--is in the process 
right now, in collaboration with our partners, the American 
Heart Association, and the American College of Cardiology, to 
update our obesity guidelines. We will have those available 
soon for adults, and importantly, for children, as well. A very 
important task is to get those guidelines implemented into 
clinical practice.

                       CARDIOVASCULAR GUIDELINES

    Another task that we are--have embarked on, Senator 
Cochran--is to develop a set of integrated cardiovascular 
guidelines. In the past, we've had guidelines for blood 
pressure, for cholesterol, for obesity, and it's really time we 
begin to integrate those.
    So, we started down that road, we're using a web-based 
tool, because we know most people, now, get their information 
through the Internet--we want this to be a consumer-driven 
project, again, in partnership with the Heart Association, the 
College of Cardiology.
    We're hoping that this is a tool by which people can 
understand their composite risk for heart disease and obesity, 
given all of these individual risk factors.
    So, the answer is yes, sir, we're working very hard at it.
    Senator Cochran. I know one other area that you're familiar 
with is the Jackson Heart Study, based in Jackson, Mississippi, 
named for the city, to try to improve our screening and 
knowledge of heart disease and things that can be done--
societal changes, diet, exercise, the like--to more 
successfully deal with that problem. What is the status of that 
project, and is there a continuing need for funding for this 
review that's being undertaken?
    Dr. Nabel. Well, thank you very much, Senator. I want to 
personally thank you for the time and attention that you have 
brought to the Jackson Heart Study. You know that it's a very, 
very important project to us at the National Heart, Lung, and 
Blood Institute, and we have worked collaboratively with you, 
and your office, as well as individuals at the University of 
Mississippi, Jackson State, and other institutions in 
Mississippi to bring this to fruition.
    We have a lifetime commitment to this project. We believe 
that this project is so important, in terms of understanding 
the origins and the development and the treatment of heart 
disease in African-Americans in this country--it's critically 
important to us, as a Nation, and we will stay steadfastly 
committed to it.

                       ADDITIONAL FUNDING FOR NIH

    Senator Cochran. Dr. Zerhouni, we're really pleased that 
the committee is moving to increase the appropriations for NIH, 
and I'm not going to make any predictions before we get through 
our work, but I think there is a consensus in this committee to 
do just that. What would an additional $1 billion increase do 
in terms of practical consequences at NIH in what you're able 
to accomplish?
    Dr. Zerhouni. You said $1 billion?
    Senator Cochran. Yes.
    Dr. Zerhouni. Okay. If I had my choice, the first thing I 
would do, is I would really fund and protect the next 
generation of scientists. I would create a lock box within the 
budget, and say, we need to absolutely fund the next 
generation, and it has to be that number, and come hell or high 
water, we will fund them. So, the first thing is protect that 
future of protectors, who are going to follow these clues--if 
you don't have them, you don't have a research enterprise. 
That's number one.
    The second is to address what I think are important 
resources across the entire Nation that are absolutely needed 
to conduct clinical trials, they are like what Dr. Niederhuber 
was talking about--to do, and you want to conduct research--we 
have to have the physical resources to do that, and to allow 
laboratory tests, to allow screening, for example, of millions 
of compounds, when we have a lead, or a target.
    Dr. Collins was talking about the investment we made 
through the Roadmap through chemical genomics. With the 
robotics technology that we've implemented at NIH, we can do 
1.5 million tests in a day and a half. Well, you couldn't do 
that 5 years ago. That's what I would like to expand, so that 
more people have that availability.
    The third investment that I would make is engage the 
community of scientists in more integrative science. Work 
across disciplines, fund them so that at the end of the day, 
they can coordinate their work to address problems that, as I 
said in my opening statement, tend to be very complex, and they 
require the collaboration of physicists, mathematicians, 
biologists, doctors and nurses, endopediologists--all of these 
need to be able to work together. It's not so easy to do when 
you don't have the dollars to sustain that infrastructure.
    So, the third point--$1 billion won't be enough, actually, 
to do all this--is absolutely continue to encourage 
innovation--breakthrough innovation. Encourage people like the 
Pioneer Award, the New Innovator Awards, and we are launching a 
new program called Transformative R01s--we are doing it, but 
it's just not enough. We absolutely need to tell people, ``It 
is the best place to do research, America is the best place to 
do research, and we will actually give you the freedom to 
explore ideas that have been knocked out through, by all of us 
here today.''
    Those three things--young investigators, infrastructure to 
conduct better research with better resources at a faster pace, 
and give the leeway, the freedom for people to explore new 
avenues that we may not be exploring today.
    Senator Cochran. Thank you very much, thank you for your 
leadership, all of you.
    Dr. Collins, best wishes to you, as you move onto other 
interests and pursuits, thank you for your service.

                 PANDEMIC INFLUENZA VACCINE DEVELOPMENT

    Senator Harkin. Thank you, Dr. Zerhouni, for that last 
answer to that question, I thought that really laid it out, 
where we ought to be headed.
    Dr. Fauci, let me pick up with you, here, on pandemic flu. 
It's sort of, you know, we've had hearings with you in the past 
on this, and talked about the threats of pandemic flu. It's 
sort of, somehow faded to the background, although things that 
I read about and keep up on indicate that the threat is still 
there, as real as it ever has been.
    We've been trying to develop vaccines, and to--develop, I 
should say, develop systems for developing vaccines--that can 
respond to whatever the strain is that might be the outbreak.
    Most of it's been egg-based in the past, we know that takes 
a long time, and then we went into cell-based, but that still 
takes a few months, several months, to develop the amount of 
vaccines that we need. I keep hearing about other kinds of ways 
of developing vaccines in a more rapid manner, I'm not--I can't 
speak about them, I don't know much about them, and so my 
question is, what's happening with--in your shop--in systems 
developments so, to respond to a pandemic flu outbreak? To get 
the vaccines made as rapidly as possible?
    Dr. Fauci. Well, thank you for that question. Just because 
Mr. Chairman, as you well know better than anybody--just 
because something is not on the front pages anymore, that 
doesn't mean that it's not an important issue.
    So, there are two parts to your question that I can answer 
very briefly and succinctly. First, where do we stand with 
regard to a potential pandemic flu? That's not gotten a lot of 
press lately.
    Number two, what about the investments that we spoke about 
at several committee hearings that you had, that I discussed 
with you at an official hearing and in private, about some of 
the systems involved, and some of our previous lack of ability 
to scale up manufacturing of vaccines, and surge, if, in fact, 
we have the unfortunate event of a transition from an endemic 
virus that still currently is in chickens. H5NI is still 
killing a lot of chickens, in Southeast Asia, and occasionally 
we see a burst of a transmission in a particular region, with 
culling of the chickens, and then it dies down.
    The numbers now, we have about 385 human cases, 243 deaths 
as of yesterday, which gives you a sense of how the threat of 
the pandemic is emerging. That means it's smoldering, it has 
not gone away.
    What have we done from a scientific standpoint? There have 
been major advances that I welcome the opportunity and thank 
you for asking the question about, with regard to some of the 
things that we set into play a year, 2, or 3 years ago. There's 
been a significant amount of movement now by several companies 
to varying proportions, away from egg-based, more toward cell-
based, vaccine manufacturing which gives a considerable degree 
of flexibility, number one.
    Number three, and I think to myself as a scientist, this is 
perhaps the most exciting--as I mentioned to you previously, 
about a year or so ago, there is great potential for the use of 
adjuvants. As you know, an adjuvant is a compound that you give 
together with the main component of a vaccine, that we call the 
immunogen, and it has the capability of doing two things.
    It allows you to get an amplification of effect with a 
lesser dose; this is critical to stockpiling.
    Number four, and we didn't know this for sure, but we've 
seen it in a number of other studies, is that it broadens the 
breadth of the response, which means, critically, that if we're 
looking at a vaccine that's circulating in Southeast Asia now, 
and we make a vaccine from that virus, there's always the 
possibility, if not the likelihood, that if it evolves to now 
become very efficient in going from human to human, if we 
stockpile that particular virus vaccine, we're going to have to 
change it--perhaps significantly--to keep up with the evolving 
strain.
    What we have found out in three or four separate studies, 
conducted either by ourselves or together with pharmaceutical 
companies, or by pharmaceutical companies alone, is that the 
use of adjuvants has now dramatically increased our capability 
of scaling up.
    So, what was formerly the famous 90 micrograms times two 
that I told you about several times, we can get down, now, to 
7.5 micrograms, or 3.75 micrograms, times two.
    And then, the final part of that is that much to our--I 
wouldn't say surprise, because I would like to have predicted--
but much to our gratification, the response to a strain that's 
an Indonesian strain, when you vaccinate you get cross 
reactivity now, to some of the evolving strains. So, this 
really is very good news for the ability to scale up, and in 
fact, have a stockpile that would be more than just a stop-gap, 
but would actually, might afford this broader cross-protection.
    So, again, though it hasn't been highly publicized, I think 
the news is all gradually heading in the right direction.

               MOLECULAR ADVANCES IN VACCINE DEVELOPMENT

    Senator Harkin. Is there something besides cell-based 
developments that's going on?
    Dr. Fauci. There's the whole issue of the molecular-
biological approach, because the standard vaccinology is, you 
get the virus itself, whether you grow it in eggs, or you grow 
it in cells, it's still the virus itself, and then you purify 
it, spin it down, get the right components of it. That's 
standard, classical vaccinology.
    We're moving to what we call the 21st century vaccinology, 
which means you can, for example, take DNA, and insert into 
that the coding elements for a particular, specific protein, in 
this case with influenza, it would be the hemagglutinin, or the 
neuraminidase, or the M-Protein, and if successful, you can 
make an unlimited amount by the production using what we know 
from decades of experience with molecular biology, and 
recombinant DNA technology. We're starting to see that, right 
now, evolve and replace the standard vaccinology.
    Dr. Zerhouni reminded me of a question that you didn't ask, 
but you've asked me in the past, is where we are with the 
universal vaccine, namely are we making headway in that? Some 
of the animal studies, again, are looking promising. This is 
one of those real tough nuts to crack, but I hope that at a 
future hearing, we'll be able to come to you with some real 
hard data that we've actually made progress in getting a 
product that could actually handle the drifting strains as they 
evolve from one year to another.

                         AIDS VACCINE RESEARCH

    Senator Harkin. To go from that kind of good news, and 
hopeful outlook, I now go to the AIDS vaccine.
    Dr. Fauci. Yes.
    Senator Harkin. All of the years and the money that's been 
spent on that, and the depressing news that we received 
recently, that not only is the AIDS vaccine not working, it may 
actually increase the susceptibility to AIDS. So, where are we? 
Where are we heading?
    Dr. Fauci. Well, where we're heading is a bit more back to 
the fundamental basics of asking and answering some of the 
questions that I mentioned to you and this committee years ago, 
related to the fact that HIV is really very different. In 
vaccinology, in general, when we make a vaccine, the standard 
paradigm is to make a vaccine that mimics natural infection. 
Because when all is said and done, when you're dealing with 
smallpox, when you're dealing with influenza, when you're 
dealing with polio, the body ultimately induces successfully an 
immune response, and although people get sick, and some die, at 
the end of the day, that virus, that microbe induces a response 
that completely eradicates the particular microbe from the 
body.
    So, nature is smarter than we are, so when we want to make 
a vaccine, we want to mimic natural infection.
    Senator Harkin. Yeah, I understand.
    Dr. Fauci. The problem with HIV is that the body, to our 
great dismay, does not make an adequate immune response against 
the virus, such that there are essentially no examples of a 
person who gets infected, has an established infection, and 
then eliminate the virus from the body.
    The reason is the way the virus presents itself: the body 
doesn't recognize it in the way that it induces a protective 
response. So, the failures that you've been hearing about, were 
that we were hoping that with the balance between empiricism, 
and fundamental scientific concept questions, we would be 
fortunate enough to have a situation where it would work.
    It's becoming very, very clear now, that we need to go back 
and try and make ourselves smarter than the body, namely by 
developing whatever it is that--we call it an epitope, which is 
a component of the virus--and present it to the body in a way 
that would have it induce neutralizing antibodies that would 
ultimately protect.
    So, you heard about the disappointing Merck study, it was 
called the STEP study, we were partners in that. And right now, 
we're going to very carefully go ahead and raise the bar a bit 
higher, before we go ahead into a big clinical trial, and turn 
the knob more toward asking and answering some of those 
fundamental questions.
    We actually had a very successful summit in March of this 
past year, and we gathered all of the players, and even some 
people not involved in HIV vaccines, to plot the way over the 
next several years, and that's what we're trying to do.

                      CANCER AND THE IMMUNE SYSTEM

    Senator Harkin. Thank you very much.
    Well, thank you very much, Dr. Fauci, for bringing us up on 
that.
    I have a couple of things I wanted to bring up with Dr. 
Niederhuber on cancer research.
    I wanted to get your thoughts on a researcher, you may not 
be familiar with, but I hope you will look into this. There's a 
researcher at Wake Forest that I met a few weeks ago and then 
have had some correspondence with--he recently presented a 
paper at UCLA that I heard about, his name is Jiang Cui, C-U-I, 
Dr. Jiang Cui.
    He came to my attention because it was told to me that he'd 
been bringing mice with certain immune cells that were 
resistant to cancer. That no matter how much cancer cells were 
injected into the mice, the mice never got cancer.
    Then he was taking some of these immune cells from these 
mice and putting them into other mice, and when he did that, 
those mice didn't get cancer. Well, this kind of intrigued me, 
so I met with him, he had quite an interesting laptop display 
that he showed me on this. These immune cells--he called them 
granulocytes, which I've never even heard of before.
    Now, again, this is in mice--I understand mice are 
different than humans--but as someone once said, we're about 90 
percent rat ourselves, close to that, anyway. It doesn't matter 
to just politicians, I mean all of us.
    So it's very close. So, again, it raises the possibility 
that you can use the immune system cells to boost a cancer 
patient's resistance, an ability to fight the disease. Are you 
aware of his research at all? I asked him if he'd had an NIH 
grant, he said he did, once, some time ago, but he doesn't now. 
I just wondered if you were at all familiar with his research, 
at all, at Wake Forest. If not, that's fine. I just encourage 
you to take a look at it.
    Dr. Niederhuber. I'm a little bit familiar with it, 
Senator, he has had grants--two grants, I believe, in the 
past--an R01, and then an R55 that was converted to an R01. 
Both of those lapsed and he did not come back in for additional 
funding. Both of those were in areas that weren't quite related 
to what you're describing. He does have an IND which allows him 
to do research in this area, neither using these granulocytes 
that he harvests from patients nor in mouse models.
    I would only say that I think that, as you're very much 
aware, we have probably at the NCI, and also with our 
colleagues at the NIAID, some of the best immunologists in the 
world, that are working not only on infectious disease and 
inflammation, but also on the relationship of cancer to the 
immune system.
    I know that you are very familiar with the similar work in 
what we call cell-based therapy, of Steve Rosenberg. I think 
this is probably the most exciting work in the country, or 
maybe even in the world, right now, in terms of using cells 
from our immune system, tricking them or arming them in a way 
that they can specifically attack cancer.
    So, we've very excited about the progress that Dr. 
Rosenberg has made. I think he is out in front as one of the 
real leaders in this--what I would call--cell-based therapy. 
There are certainly other workers across the country, some 
funded, some not funded, that are doing some similar things, 
but I don't think any of them at quite the sophistication of 
Dr. Rosenberg.

              CONFLICT OF INTEREST IN EXTRAMURAL RESEARCH

    Senator Harkin. I'm obviously familiar with Dr. Rosenberg's 
history and what he's been doing, but it seems to me that 
that's the area that he's sort of been involved in for a long 
time, that is, the immune system and how that relates to our 
ability to fight off cancer cells. I thought of that when I met 
Dr. Cui, I thought of Dr. Rosenberg and all the work that he'd 
done in the past on this.
    But, I would appreciate it if you'd take a look at that and 
see if there's anything different there, that what Dr. Cui is 
doing at Wake Forest.
    [The information follows:]

           Department of Health and Human Services,
  National Institutes of Health, National Cancer Institute,
                               Bethesda, Maryland, August 11, 2008.
The Honorable Tom Harkin,
United States Senate, Washington, DC.
    Dear Senator Harkin: At the, July 16 hearing to consider 
Appropriations for the National Institutes of Health (NIH), you asked 
me to look into research done by Dr. Zheng Cui at Wake Forest 
University. Several scientists at the National Cancer Institute (NCI) 
have had the opportunity to examine Dr. Cui's work which is indeed very 
interesting. In the course of routine experimentation, Dr. Cui 
discovered a single male mouse that did not develop cancer despite 
repeated infusions with increasing numbers of cancer cells known to 
cause cancer in other mice. When he bred this mouse, he found that 40 
percent of its progeny also proved resistant to cancer suggesting that 
there was an inherited genetic element to the observed resistance. 
Further experimentation has demonstrated that the immunity displayed in 
these mice is mediated by cellular elements of the immune system, 
called, as indicated at the hearing, granulocytes. The cellular 
immunity has proven to be effective against multiple types of cancer 
and has proved transferable. Injection of previously susceptible mice 
with granulocytes from resistant mice has conferred cancer resistance 
to the recipients. If the recipients already had cancer, the tumors 
regressed. Dr. Cui has not however been able to isolate the genes in 
the resistant mice responsible for this characteristic, postulating 
that this may be due to the fact that they are mobile genetic elements, 
genes that do not have a fixed location on a chromosome.
    It is unclear what experiments were done with human granulocytes to 
determine that they too displayed the cancer resistance found in the 
mice. Perhaps an in vitro assay of the ability of these immune cells to 
kill a variety cancer cells would be informative. While in vitro 
experiments might be encouraging, there is not yet reason to believe 
that granulocyte infusion from a donor would have in vivo anti-tumor 
activity and no evidence to suggest that the infused granulocytes will 
traffic to tumor sites. An additional concern is the potential risk of 
graft versus host disease which is not a concern in the experimental 
mice, but would certainly be in humans. Dr. Cui's planned trial will 
attempt to determine the risk of this complication in which donor cells 
(lymphocytes) attack healthy cells in the recipient, leading to serious 
health problems. While the trial design only calls for the infusion of 
granulocytes, there is no guarantee that all lymphocyte contamination 
would be removed.
    This approach differs somewhat from that of Dr. Steve Rosenberg. In 
Dr. Rosenberg's case, the transferred cells are lymphocytes which have 
been proven to have anti-tumor activity in vivo. In addition, Dr. 
Rosenberg's research now involves the use of the patient's own cells in 
the treatment of cancer rather than donor cells. The patient's cells 
are genetically modified outside of the body in order to increase their 
anti-tumor activity and are then infused back into the patient.
    Dr. Cui's approach, while interesting does make certain leaps of 
faith with regard to the similarities between the mouse and the human. 
The upcoming clinical trial will determine whether these leaps were 
warranted. I appreciate your interest in cancer research and am pleased 
to have the opportunity to provide this information to you.
            Sincerely,
                                 John E. Niederhuber, M.D.,
                               Director, National Cancer Institute.

    Senator Harkin. I just have one other area that I really 
wanted to cover here, Dr. Zerhouni, conflict of interest. You 
led the way on changing the rules for NIH employees. I know you 
share my concerns about conflicts of interest among extramural 
investigators, as well. We have to maintain the public's trust 
in NIH, and eliminating conflict of interest is an important 
part of that.
    I know you supported the amendment I offered in last 
month's Appropriations Committee markup to require HHS to issue 
``an advanced notice of proposed rulemaking,'' which will start 
the formal process of revising the current HHS guidelines.
    Clearly, NIH and academic institutions will have to work 
together to end the problems that we've been reading about. 
There's obviously been some correspondence from other Senators 
in this regard and some of this has made its way into the 
press.
    The HHS Inspector General recently found several problems 
with the way NIH is currently overseeing grantee institutions. 
For example, NIH couldn't provide an accurate count of the 
number of conflict of interest reports it had received. More 
importantly, the AIG found many Institutes basically take 
grantee institutions at their word, that they're following the 
regulations, rather than doing any oversight of their own.
    Again, in your opinion, what should NIH be doing to improve 
its oversight of the extramural research that's being done, and 
any problems of conflict of interest in that extramural 
activity?
    Dr. Zerhouni. As you know, the issue of conflict of 
interest has sort of grown in importance over the past 15 
years, much more so than ever in our history, simply because of 
the intertwining of industry and academia, in terms of 
marketing and understanding the proper use of drugs.
    We also need to state that there is good value to good 
interactions that are well-managed, between industry, academia, 
and Government that create public good. Many of the discoveries 
and the products that we make, come from that interaction.
    So, the real challenge, Senator, is how do you balance, the 
good--the public good--that comes in from proper, fully 
disclosed, fully understood interactions that do not--do not--
present a risk to either individuals, human subjects, or the 
risk to the objectivity of the science?
    So, we need to work together, NIH, the institutions, 
Congress, to find exactly how this needs to be put in place. 
Given the fact that the world has changed, and given the fact 
that I think our number one priority is to make sure that the 
American public who funds this research is ensured that we have 
systems in place, common standards in place, that are 
transparent that allow us to also stratify the risk.
    I don't believe there is the same degree of risk in terms 
of conflict of interest when you're talking about very early 
discovery or genetic research that doesn't have a human 
application, as opposed to a clinical trial. As opposed to 
teaching, giving opinions that are not evidence-based, or using 
scientific prestige to promote private interests.
    That gradient, if you will, that stratification, needs to 
occur. So, what I'm hoping for is that, and something I've said 
all along, is that we need to come up with a consensus about 
common standards that all institutions need to use. If you 
really look at the Inspector General report, our own analysis, 
you'll find that institutions have not yet converged toward one 
common, coherent set that we can all implement, that's number 
one.
    Number two, I think it's important to stratify the risk. I 
think it's different when you're talking about risking the life 
of someone, or imposing treatments that are not evidence-based 
on thousands of individuals, as opposed to doing good research 
that may discover the next cure for a disease.
    I think we need to understand that better, and I think the 
advanced notice of rulemaking will establish that debate, so 
that we understand that.
    Third, I believe that there is a cultural responsibility 
that is absolutely necessary for that. The first thing that has 
to happen is sunshine. So, I think I support the concept of 
sunshine in disclosing these relationships, first and foremost.
    The second step after sunshine, is to understand how you 
manage those things to, guarantee the integrity of the process. 
You can't do that, really, in my opinion, without some third 
party that will be the arbiter of this between institutions and 
the NIH.
    So, we need to think about some independent way of really 
being proactive, if you will, a sort of quality control over 
the process. It's really hard for NIH to, essentially, check 
300,000 scientists out there, We don't have to rely on some 
degree of self-regulation, self-reporting, and I think that is 
the challenge that we all face.
    We all want the same thing, which is let's not discourage 
innovation, but not at the expense of either individuals, or 
the integrity of the scientific process.

                      AAMC AND AAU RECOMMENDATIONS

    Senator Harkin. I'm assuming, Dr. Zerhouni, you would 
support the AAMC and the AAU recommendation that investigators 
should have to report all of their financial interests? 
Regardless of the amount, regardless of whether it might appear 
to be affected by their research? That's the idea of just 
sunshine, are you supporting that?
    Dr. Zerhouni. I think so. I think we need to do that and 
actually when we looked at the issue at the NIH, one of the 
problems was lack of disclosure. I mean, you can't manage 
something you don't know about, right? I mean, how do you start 
managing something when there is no disclosure requirement? I 
think that's the number one step.
    I think we also need to be very careful not to go too far 
and damage innovation by having very strict rules that are one-
size-fits-all. I'd be willing to be very, very strict when it 
comes to risk to patients, risk to populations, and risk to the 
integrity of science. That's different than someone who has a 
patent, a discovery, a new device or a brilliant idea--I don't 
think we want to stub that, so reaching the balance is the key 
concept here, while preserving public trust.

                         FOOD ALLERGY RESEARCH

    Senator Harkin. I keep shifting back and forth, but I 
forgot to ask Dr. Fauci another question.
    In my other capacity as chairman of the Agriculture 
Committee, which has to do with a lot of food programs, and 
feeding programs, next year we have the reauthorization of the 
child nutrition bill, which provides funds for school lunch 
programs, school breakfast programs. Through all of this, I 
think maybe we've talked about this in the past, and I'm sure 
I've asking you about this at other hearings--the seemingly 
explosion of food allergies among kids.
    Dr. Fauci. Right.
    Senator Harkin. I'm hearing back from school that are 
having problems, because of all of the food allergies that kids 
have. So, what's happening out there, and what's your Institute 
doing to look at this, seemingly, explosion of food allergies?
    Dr. Fauci. Yes, that's a very, very important issue, in 
fact, you recall we had a hearing just on this particular 
subject. A lot is happening now, I think that there really is a 
full realization that this a serious problem. As you know, 6 to 
8 percent of children less than 4 years old have a food 
allergy, and 4 percent of adults have a food allergy. There are 
30,000 anaphylactic reactions a year, and about 150 to 250 
deaths.
    So, we really need to, actually--and this is what I believe 
we're on the way to being more successful than we were in the 
past--of rejuvenating the field along the lines that Dr. 
Zerhouni and Dr. Collins and everyone was talking about about 
getting people in the field who are interested, who are 
motivated to get involved, bring some of the more sophisticated 
science to try and understand what is the pathophysiological 
mechanism of why this is occurring, asking whether some of the 
old assumptions that we have about food allergies, including 
things like peanut allergy should we be exposing early or 
avoiding? Things like that.
    Senator Harkin. Which I asked you about at that hearing, 
remember? I mentioned to you----
    Dr. Fauci. Exactly, exactly.
    Senator Harkin. That, why China--they eat all those peanuts 
in China, and they don't have allergies?
    Dr. Fauci. Exactly--they boil them, we roast them.
    Senator Harkin. There's something going on.
    Dr. Fauci. In Israel, they give infants and children 
peanuts as a little snack, we don't.
    So, there are so many fundamental questions and I'm so 
pleased, we had a hearing with Senator Dodd a few months ago, 
about what's going on in food allergy, and we're very pleased 
that we have a program of a new investigators. We are trying to 
ask some fundamental concept questions, hoping to bring new 
people into the field. We have committed about $5 million over 
2 years and we're just now in the process of awarding those 
grants. To my great satisfaction, I think 11 out of 12, or 
maybe even 12 out of 12 of the investigators are actually 
people new to the field. That's very important when you think 
in terms of the things that Dr. Zerhouni said, about getting 
new, fresh, young ideas.
    So, we have--in a very limited budget, I have to say--we've 
increased our food allergy allocations from a pittance of just 
less than $2 million to close to $13 million, but we really 
need to do much more, but in an arena of fiscal constraint, 
it's very difficult to do. So, we're really trying to jumpstart 
that system. But, I'm very pleased that you, and Senator Dodd, 
have brought that up, because it is now really focusing on the 
importance of the problem.
    Dr. Zerhouni. If I may, Senator, also as part of the 
National Children's Study, there is a component of the 
Children's Study that is going to look carefully at this from 
the moment of conception, all the way to 21 years of age, 
trying to capture, in fact, the food exposures, if you will, 
that we have and the emergence of allergy, trying to understand 
a little bit better what happens in early life. Dr. Dwayne 
Alexander is not here, but I'm sure he would have mentioned 
that and I think we've updated your office on that.

                        HEART ATTACK PREVENTION

    Senator Harkin. I'm going to reassure you that we are going 
to continue to fund the Children's Study. We're not going to 
let that one drop, either. We're going to continue to fund 
that.
    I was, Dr. Nabel, I haven't asked you a question and I 
wanted to get to one thing. Since Tim Russert's death, we get a 
lot of people asking about, what are we doing to really prevent 
heart attacks? It seems like kind of random, and they happen, 
I'm just getting a lot of input into my office about that, 
they're going to their doctors, are they a risk for heart 
attack--what kind of research is being done in preventing heart 
attacks?
    Dr. Nabel. Well, that's a very important and delicate 
question. Mr. Russert's death was a great tragic loss for our 
country and many of us have mourned his death.
    We have now referred to this as the Russert Effect, you've 
probably seen stories in the newspaper, on television, of 
middle-aged men--a story in the Times a week ago, a middle-aged 
man, age 50, on a bike ride on a Saturday morning, didn't feel 
well, a little fatigued, a little short of breath, his partners 
had to leave him behind. He called his wife, ``I'm not well,'' 
he went home, laid down, and thought, ``Tim Russert.'' He drove 
himself to the hospital and he was having a heart attack.
    It is true that we know a lot about the risk factors for 
heart disease and we're doing all we can to help individuals 
identify their risks very early in life and modify those risks.
    Yet, at the end of the day, despite all of our best 
abilities to modify those risks, we know that at some time, a 
little bit of the blockage in the heart artery can break off, 
and that blockage might only be a 5 or a 10 percent blockage, 
might break off, leading to a blood clot and a heart attack.
    That doesn't stop us from doing everything we can to help 
individuals understand their risk, and to help them to do all 
they can to modify their risk. As you know, we've had a very 
active program over the past 5 years for women and heart 
disease to have women identify the risk.
    I think, quite honestly in all of our efforts to focus on 
women, we've left the men behind. Now we need to catch up, and 
help men remember that they're at great risk, as well.
    It's really a public education, it's a campaign that we 
work on arduously, every day, with our partners, the American 
Heart Association, to help people understand their risk, and to 
take action.

                         STATINS AND MORTALITY

    Senator Harkin. Is there any evidence, at all, any medical 
evidence at all that the use of statins has reduced mortality--
    Dr. Nabel. We know that the use of statins lowers your risk 
for having a heart event--by that I mean, a heart attack, or 
dying of a heart attack.
    Senator Harkin. Because I've been informed that there 
really is no medical evidence that statins has reduced either 
morbidity or mortality from heart attacks.
    Dr. Nabel. For people who have known heart disease, the 
answer is yes, statins clearly reduce the risk for having a 
second heart attack, or for dying from heart disease.
    Senator Harkin. Which raises the question, should so many 
people be taking statins, who have never had any incidents of 
heart disease at all?
    Dr. Nabel. That's exactly the question that needs to be 
asked, and that's the study that we would love to do. If we had 
incremental money in our budget.
    Senator Harkin. But we're spending billions of dollars a 
year taking statins----
    Dr. Nabel. We are.
    Senator Harkin. There's a lot of counter-evidence that they 
really--unless you've had an incident----
    Dr. Nabel. Yes.
    Senator Harkin. That it really doesn't prevent.
    Dr. Nabel. You're right, Senator. What we're really doing, 
is we're hedging our bet. Because what we don't know, is that 
for individuals who are at low, or even moderate, risk for 
heart disease, does starting taking a statin--age 20, age 30, 
age 40, age 50, or even in childhood--make a difference? We 
don't know the answer to that question.
    We know that if you're at a very high risk for heart 
disease, then you've got very high LDL cholesterol, and you've 
got two, three, four other risk factors, then yes, in that 
group, taking a statin does help.
    But, the majority of people really taking statins in our 
country today are people who are hedging their bets. A little 
bit of an increase in blood pressure, a little bit of an 
increase in cholesterol, figure lowering your statin may be 
helpful. It's common judgment, it may be helpful, but we don't 
know the answer.
    The study that we would like to do, is a longitudinal study 
of primary prevention. Does taking a statin when you start, 
say, in your 30s or 40s, when you might have one or two risk 
factors for heart disease, does that lower your risk, or 
prevent you from getting a heart attack in your 50s, 60s or 
70s, or dying from heart disease? We would love to do that 
study, if we had the money.
    Senator Harkin. Why don't you do that study?
    Dr. Nabel. We would love to, it's an expensive study.
    Senator Harkin. Well, tell me how much.
    Dr. Nabel. We're estimating that----
    Senator Harkin. I mean, if not today, I mean, at least----
    Dr. Nabel. Yes, it's in the estimate of hundreds of 
millions of dollars. Because you would need to enroll people 
very early in life, you would need to follow them carefully 
over decades--we could certainly do that study. We've done an 
equivalent in the Framingham Heart Study, we're doing it in the 
Jackson Heart Study.
    But, at this point, to dedicate that size of sum of money 
from our budget, which is limited, it's just tough to do.

                         CARDIOVASCULAR DISEASE

    Dr. Zerhouni. If I may, from the overall standpoint, not 
looking specifically at this--if you look at the total 
mortality and morbidity for cardiovascular disease and stroke, 
it has dropped by 60, 70 percent. The real question is how do 
you and what do you attribute that drop to? Is it cessation of 
smoking? Is it taking aspirin? Is it taking, having good diets? 
There's controlling blood pressure, taking statins.
    So, when you look at the policy aspect of this, how do you 
really start demonstrating whether or not something works or 
doesn't work? Well, you have to take the high-risk group. In 
this case, in statins, it's clear that if you take patients who 
have had a heart attack, therefore, absolute proof-positive 
that they have an underlying cardiovascular disease, the 
evidence is clear that statins do help reduce the number of 
second events, and so on.
    The same thing is true when you're looking at the issue of 
secondary prevention, versus primary prevention, which is the 
topic that Dr. Nabel talks about. As a country, we're going to 
have to make that decision, why? Because there are many things 
we do, for example, in diabetes. Diabetes, we have oral drugs 
that reduce glycemia. We have, also, studies that NIDDK has 
done that show that if you use them as a pre-diabetic patient, 
when you're not diabetic, you will reduce the risk of the 
disease emerging.
    What is the key to all of this? The key, Senator, is can we 
predict in the millions of people who take statins, those who 
have a real risk, as opposed to those who do not have a real 
risk? That's where the predictive nature of the genomic 
research and the personalized medicine research that Dr. 
Francis Collins has been talking about comes in. As long as we 
don't have that knowledge, you know we will have to do very 
long trials where we follow people over many years, which are 
very costly.

                 BIOLOGY OF AGING AND THE AGING PROCESS

    Senator Harkin. Speaking of long years, Dr. Zerhouni, I 
want to talk about the biology of aging. Diseases like 
Alzheimer's, you mentioned diabetes, heart failure, stroke--
operate in different ways, but the one thing that they all have 
in common, they tend to strike older people.
    Traditionally, our research in these diseases has 
approached them separately, one at a time, we look at these 
diseases, and we investigate them. Now, we're learning more 
about the basic biology of aging, that suggests there may be 
ways to postpone all of these diseases, by slowing down the 
human aging process.
    If we could add 5 to 7 years of healthy, vital life to 
millions of people, it would have an enormous impact on 
healthcare spending. Plus, the fact that we know that most of 
the spending on medical care in this country goes in the last 
couple of years of life.
    Someone once said to me, a long time ago, that one of the 
primary goals of biomedical research was to enable to die 
young, as late in life as possible. I've always remembered 
that. So, what are you doing, what are you looking at in terms 
of this whole biology of aging and the aging process, as it 
might impact all of these different--heart diseases, strokes, 
diabetes, and everything else?
    Dr. Zerhouni. Right.
    Senator Harkin. I imagine that must spill over into Dr. 
Collins' area, too, big-time.
    Dr. Zerhouni. I will start and then he'll tell you what the 
future is like.
    Clearly, when you look at the aging process, and you 
started by saying, there are multiple conditions that affect 
people at the same time.
    Senator Harkin. Yes.
    Dr. Zerhouni. So, there are really two questions, there 
are--do we age the same way? Does our population age in the 
same way, or do we have clusters? People age one way and then 
others age another way?
    So, the first thing is, is there a heterogeneity in aging, 
do we all age in the same fashion? We know, today, that the 
aging process over the past 30, 40 years--people are living 
longer and healthier, so the disability rates for seniors have 
dropped. So, we know that there are things you can do that seem 
to improve your aging process.
    Second, we also know, as Dr. Nabel was just mentioning, and 
she's saying something very important--we've done one disease 
at a time, now we need to integrate the factors, and it's very 
clear that if you look at the aging process, some of us age 
faster, and seem to present a collated set of diseases--
diabetes, high blood pressure, the metabolic sort of--low 
exercise levels, obesity, Alzheimer's disease that relates, 
now, as we know, to diabetes in some ways, and cardiovascular 
disease. You look at the genetic spectrum of these diseases, 
one subgroup seems to be affected more than other subgroups, 
and we are honing down on those discoveries.
    So, that's one aspect of the aging process. Are we 
accelerating unhealthy aging in certain members of our 
population, what is the evidence that that's the case, and what 
can we do about it? So, that's one way to approach the problem, 
Senator.
    The second problem is we also have evidence that you can, 
in fact, slow down the aging process. So, we have found a 
molecule--there's a famous molecule now, retro, which comes 
from red wine, which seems to be, in fact, having this effect.
    The other remarkable finding is that if you have caloric 
restrictions--if you just reduce the number of calories in an 
experiment in animals, you can lengthen life expectancy by 30, 
40 percent.
    Our researchers at the NIA are doing another experiment 
where they're saying, what if you have one day of fasting and 
another day where you don't fast? So, intermittent fasting? 
They see the same results, even without loss of weight.
    So, there's fundamental research on one end that shows that 
there are mechanisms that complex network of molecules that 
say, there is a way of good, graceful, healthy aging. There's 
also this body of research that shows that, in fact, chronic 
diseases seem to start in a combinatorial way where you seem to 
have everything at once and then you have to take 12 drugs to 
live your life and those are not the exact same processes.
    Well, now I'll turn it over to Francis, who's done a lot of 
work with NIA about how do we, then, see the future in these 
two directions?

                           GENETICS OF AGING

    Dr. Collins. So, despite all of the exciting research 
that's going on, I think you're right, Senator, that the goal 
ought to be to try to give each of us the chance to die young, 
but at a very old age.
    The death rate will probably continue to be one per person, 
at least that's my prediction in the current climate.
    But I'd like to see that death rate extended out, to a full 
four score and ten or more for all of us.
    So, how are we going to get there? Obviously a great area 
of interest is what is the program that's basically built into 
our system that is supposed to be responsible for the fact that 
we don't live forever? In evolutionary terms, there needs to be 
such a program, otherwise, nothing could ever really progress, 
so lifespan has to be limited so future generations can have 
the resources, and let the older generations fade away.
    But, obviously, we've learned a lot about the way in which 
different individuals seem to age at different rates, simply by 
observing them--what's going on there?
    There are studies now underway looking specifically at 
individuals who have reached the age of 100 or more, to ask the 
question, do they have some genetic susceptibility to very long 
lives? This is not a susceptibility to disease, this is the 
opposite side of that, the flip side of the coin.
    In fact, there are, in the last couple of months, 
discoveries of exactly those kinds of genetic factors--based on 
the same strategy that Dr. Zerhouni talked about in his opening 
statement, that led to all of those banners on the chromosomes 
for various diseases--there are also genes that are good for 
you, apparently, and that are capable of giving you this kind 
of opportunity to live a long and healthy life.
    If we understood how those worked a little bit better, then 
perhaps by modifying diet, lifestyle, we would contribute those 
same opportunities to people who don't have the inheritance--
the genetic endowment--that they wish they did.
    Another area that's of great interest, is studying nature's 
surprise experiments of individuals who have a very rapid aging 
process. Dr. Nabel and I, in our own research laboratories, are 
working on a disease called progeria, which is the most 
dramatic form of premature aging. These kids appear normal at 
birth, but by about a year of age, they stop growing, and then 
their hair falls out and their skin gets old and leathery, and 
they die, generally, at age 12 or 13, of a heart attack or a 
stroke. So, they're aging at about seven times the normal rate.
    My laboratory identified the genetic glitch in progeria 5 
years ago, and it turns out to be in a gene that codes for a 
protein that had some fair amount of cell biology work already 
done on it. In just 5 years, we have gone from a complete 
enigma of what this rare disease was all about, to a clinical 
trial of a drug which appears to work quite well in an animal 
model. This trial being conducted in Boston, and now already a 
year along, with about 30 kids with this rare disease being 
treated.
    That is breathtakingly quick, and it, again, is a 
testimonial to the richness of the research environment that's 
being created by NIH investments.
    Is that disease anything like normal aging? Well, obviously 
it's dramatically accelerated, but we have now very strong 
evidence that that same pathway is just a little bit tweaked as 
we get older, and maybe part of the time clock that we're all 
living with, hearing that ticking in the background, coming 
from this same pathway.
    Therefore, studying the rare disease may teach us something 
about the common, universal feature of aging, which is a very 
exciting series of observations we can expect to make in the 
next few years.
    Senator Harkin. Well, that's very provocative.
    Dr. Collins. Indeed.
    Senator Harkin. In a good way.
    Dr. Collins. Yes.

                    PROMISE OF PERSONALIZED MEDICINE

    Senator Harkin. Is there anything anybody else wanted to 
bring up here, that wasn't probed, or asked or anything? Any of 
you want to make any other--Dr. Collins?
    Dr. Collins. If I could, again, because it's my last 
chance, I think it has been mentioned by Dr. Zerhouni and 
others about personalized medicine, and I just wanted to say a 
word about that, in terms of the promise that this provides for 
where we may be able to go, in terms of clinical care.
    We are learning, as you saw in the course of the last 
couple of hours, a remarkable amount about hereditary risk 
factors for disease. We've known they were there, we largely 
guessed at them by family history, everybody has a family 
history of something, and generally that gives us a clue about 
our own risks, and it's been the best clue we've had.

                         HERDITARY RISK FACTORS

    But, we're unraveling--especially in the last 2 years--the 
molecular basis of those hereditary factors, at a prodigious 
pace. It's no accident that Science magazine called this the 
breakthrough of the year in 2007, in all of science was this 
understanding of human heredity and how it plays a role in 
common disease.
    That really does position us, relatively soon, to be able 
to offer to anybody who wants the information, a chance to find 
out, in a much more precise way, what their risk factors are--
while they're still healthy--and then to design a plan of 
prevention that is the one-size-fits-all approach, not anymore 
it's focused on what that person most needs to pay attention 
to. That's pre-emptive, that's personalized, it's all of the 
things that Dr. Zerhouni is talking about in terms of where we 
need to go. It focuses on prevention, and spending our 
healthcare dollars keeping people well, instead of waiting 
until they're in the ICU for something that we might have been 
able to prevent.

                            PHARMACOGENOMICS

    On top of that, we're learning a prodigious amount about 
the way in which drug responses also vary from person to 
person, allowing us--in the not too distant future--to do a 
more evidence-based assessment of which drug should that person 
get, and at what dose.
    Senator Specter, who courageously is going through this 
experience with Hodgkin's disease--if we had just a bit more 
information, and we desperately need to get that--to pick 
exactly the right kind of combination of chemotherapies for his 
particular situation, as opposed to a larger group of people, 
we could have an even better shot at reducing the likelihood of 
side effects, and improving the outcome, and we need to really 
push on that. But we're getting there at a pretty fast rate.

                          THERAPEUTIC TARGETS

    Then, the therapeutics that we have to offer which, in many 
ways, we have been sticking with drugs that work pretty well, 
for decades, but we've really needed this breakthrough in an 
idea about new targets--that's what the genome has given us. 
For most of the pharmaceutical industry's history, they've been 
limited, pretty much, to working with 500 or 600 targets--the 
things that we knew something about. The human genome breaks 
that wide open, and all of these discoveries about genes for 
common disease are pointing us much more precisely toward 
targets that are not secondary in the problem, they're the 
primary place that you would want to go to apply your 
therapeutics.
    We can see that happening for common diseases, and the drug 
industry is jumping on that appropriately, and for rare 
diseases, NIH has the chance to step in, and for neglected 
diseases of the developing world, as well, as we've recently 
seen done for some of those diseases like schistosomiasis.
    So, I think, when we put that all together, we have a 
pretty exciting shift in the paradigm from waiting until 
illness strikes and hoping you have something to do for it, to 
focusing on prevention in an individualized way--which I think 
will motivate people a lot more to actually act on the 
prevention opportunities, because it's about them--it's not 
some sort of generic prescription--and the opportunity to 
change our therapeutic agenda in a direction that's much more 
rational and evidence based.
    But we can't get there without the support of this 
wonderful Congress, and this subcommittee that you've so ably 
led. I think we all come here today in hopes that the difficult 
times of the last few years may be about to turn a corner, and 
that we can bring back into the fold, investigators who are on 
the edge of departing, and not returning. That's our hope. We 
don't want to see all of this done in Singapore. It would be 
great if a lot of it got done right here in the United States 
of America.
    Senator Harkin. Your remarks remind me, number one, that's 
why it is so important to pass the Genetic Information 
Nondiscrimination Act.
    Dr. Collins. Absolutely.

                       INDIVIDUAL GENOME MAPPING

    Senator Harkin. Second, are we going to be able to afford--
where do we get the price of mapping each of our own genes, 
like Dr. Watson did, and others, I mean, now what is it--
$100,000 or something, and they wanted to get it down to just a 
few hundred dollars per person, is that really going to happen?
    Dr. Collins. Oh, absolutely. We are on that pathway at a 
remarkable rate. In the last 2 years, two very new strategies 
for doing DNA sequencing have found there way, really, into the 
mainstream of this research arena, and one can now sequence a 
genome--which originally cost us, as you reported, somewhere in 
the neighborhood of $300 million for that first one. It can now 
be done for about $100,000, and the trajectory we're on, I 
would predict, will get us to the $1,000 genome in the next 6 
or 7 years.
    Already, now, one can--if you don't want the whole 
sequence, if you want to focus on, say, 1 million places in 
your genome where we know there are variations that might play 
a role in disease--you can do that, now, for about $1,000, in 
fact, there are companies out there that are marketing that 
directly to the public, which is an exciting thing, although 
some of us are a little worried about whether we're jumping the 
gun, here, in terms of knowing exactly what people should do 
with that information, but it's coming very fast.
    The technology, the cost, are not going to be rate-
limiting, what's going to be rate-limiting is to do the 
research to know what to do with that information so that 
people, once they have it, can be given good recommendations 
about how to reduce that risk and stay healthy, and that's a 
huge agenda for NIH right now, but those are--as you've heard--
expensive, longer-term clinical studies--we should be doing 
them now, and not putting that off.
    Senator Harkin. I'm hopeful that sometime in the near 
future that we're going to find some--a dedicated source of 
revenue for NIH. I've got some thoughts on that, in fact, 
Senator Mark Hatfield and I had proposed that back in 1994.
    Dr. Collins. I just remembered that, Senator.
    Senator Harkin. 1994 we proposed that, of course everything 
came crashing down, but maybe we'll revive that again, to get a 
dedicated source of revenue.
    Well, it was very simple. It was everyone's health 
insurance policy would take a certain--and it was only just a 
few pennies, it wasn't very much--that would go for basic 
medial research to enhance prevention.
    Well, I have never given up on that.
    But, Dr. Zerhouni?

                    DR. ZERHOUNI'S FAREWELL REMARKS

    Dr. Zerhouni. I'd like to just say two things--one is, 
1,000 years from now, when people look back at 2007-2008, one 
of the things they'll remember is the impact of the human 
genome on the history of mankind. When $1,000 genome, or $100 
genome--whatever it is--people will remember that as a defining 
event of the first decade of the 21st century.
    The second is that, as they look back and they wonder about 
where were the Seven Wonders of the World then? As we do today 
with the pyramids and Taj Mahal, and I would say that they will 
remember that of the seven most wonderful institutions of that 
time, NIH was part of it.
    As part that, I have a great privilege to have been, to be 
the Director of NIH, and to have been working with great 
colleagues.
    So, I'd like to add my voice to both the appreciation we 
have for you, and for the members of the subcommittee and for 
your continuous understanding and support, and I'd like to take 
this opportunity to also add my voice and those of my 
colleagues at NIH to really wish Dr. Collins the greatest 
possible future. He's been an enormous asset to our country, 
and to NIH, and I don't know if protocol allows, but I think we 
owe him a round of applause.
    Senator Harkin. Well, I join with you, Dr. Zerhouni.
    Dr. Collins, you know the high esteem that I personally 
have for you, and I know that all of the members of the 
subcommittee--I know I can speak for my great friend Arlen 
Specter, too--we have the highest esteem for you. We thank you 
for all of your dedication to health, to research, and to the 
goals of research, which is to help us live healthier lives.
    So, we wish you the best in whatever endeavors you're going 
to pursue and don't get too far away, we're going to need to 
call on you every once in a while, you know, to tell me things 
which I might understand 5 percent of, okay?
    Dr. Collins. Call me anytime.
    Senator Harkin. I appreciate that.
    Well, thank you all, very much.
    Dr. Zerhouni, thank you for your great leadership, Dr. 
Fauci, Dr. Nabel, Dr. Niederhuber, all of you. Through you, to 
all of the other Institutes. Like I said, only because of time, 
and I had a farm bill that I had to get through this year that 
just kept going on and on and on and on, and other things, and 
we just weren't able to have the kind of hearings that I like 
to have with NIH.
    But, I can assure you that--even if I'm not chairman next 
year Senator Specter will allow me to do that next year. We're 
going to have more at-length hearings with all of the 
Institutes next year.
    But, again, thank you all very much for being here, thank 
you all for your great leadership in so many areas. We 
appreciate it.

                     ADDITIONAL COMMITTEE QUESTIONS

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

               Questions Submitted by Senator Tom Harkin
                               K30 AWARDS

    Question. Dr. Zerhouni, thank you for your continued leadership in 
supporting the transformation of clinical research and clinical 
research training through the establishment of the Clinical and 
Translational Science Awards (CTSA) initiative. As the NIH transitions 
to the CTSA program, there is the potential for an institution which 
has not yet been awarded a CTSA grant to also have its K30 Clinical 
Research Curriculum Award phased out. Because not every K30 award 
recipient institution will receive a CTSA grant, it seems to make sense 
to continue the K30 mechanism for those institutions which have not 
received a CTSA grant. Does the NIH and the NCRR have a plan for the 
continuation of K30 awards to those institutions not receiving a CTSA 
grant?
    Answer. The K30 program supports curriculum development and has 
proven to be an extremely effective career development activity. The 
program was initiated in fiscal year 1999 following recommendations 
from an NIH panel on clinical research and expanded to 43 awards in 
fiscal year 2000. The program was re-competed in fiscal year 2005, when 
the average grant cost was increased from $200,000 to $300,000, and 51 
K30 grants were awarded. The last year of funding for these grants is 
fiscal year 2009. Curriculum development is a core feature of the CTSA 
program, so 31 of the K30 awards have already merged into the currently 
funded CTSA sites. For the remaining 20 institutions with K30 awards, 
most are well positioned to succeed with CTSA applications.

                             VACCINE SAFETY

    Question. Dr. Fauci, given the increased rates of refusal for 
immunization, the hesitancy of parents who do allow their children to 
be immunized, and the increased, but fortunately small, outbreaks of 
vaccine preventable diseases such as measles, please tell us: What 
resources of the NIH have been allocated to address increasing public 
concerns about the safety of the U.S. childhood immunization program?
    Answer. The NIH has three broad goals in vaccine research: (1) to 
identify new vaccine candidates to prevent diseases for which no 
vaccines currently exist; (2) to improve the safety and efficacy of 
existing vaccines; and (3) to design novel generic vaccine approaches, 
such as new vectors and adjuvants. To carry out these goals, the NIH 
supports basic and applied research at 18 Institutes in fields such as 
immunology, microbiology and disease pathology. Scientific knowledge 
gained through this basic research provides the foundation to develop 
new or improved vaccines, treatments, or diagnostics.
    NIH does not categorize vaccine safety research funding separately 
from vaccine research and development funding. Rather, NIH considers 
vaccine safety to be an integral component of all vaccine research and 
development. NIH spent just over $1.3 billion on vaccine related 
research in fiscal year 2007 and estimates $1.3 billion for spending in 
subsequent years. Federal regulations require that vaccines undergo 
extensive testing before they can be licensed and distributed. At the 
NIH, the evaluation of vaccine safety is an essential part of every 
vaccine clinical trial that we sponsor. Study participants are closely 
monitored for any adverse effects of the vaccinations they receive. In 
addition to research on new vaccines, the NIH devotes substantial 
resources to developing improved vaccines that are more effective and 
have fewer side effects than currently licensed vaccines. The NIH also 
pursues research to address specific vaccine safety research hypotheses 
as they arise. For example, several years ago the NIH supported several 
studies to find out more about the effects of thimerosal (ethyl 
mercury) exposure and how it compares with published data on methyl 
mercury exposure.
    Question. Please provide information on resource levels for the 
past 3 years and for 2009 as proposed, and separate out those funds for 
smallpox and bioterrorism-related vaccines?
    Answer. The NIH has provided the total funding levels for 
bioterrorism vaccines for fiscal years 2006-2009 in the table below. 
The NIH does not have funding available for small pox vaccines; 
however, the NIAID conducts Category A Pathogen Vaccine research which 
includes the microbes that cause smallpox, anthrax, plague and others. 
The funding levels for Category A Pathogen Vaccine research for fiscal 
years 2006-2009 for NIAID only are provided in the table below.

                                            [In millions of dollars]
----------------------------------------------------------------------------------------------------------------
                                                                          Fiscal year
                   Disease                   -------------------------------------------------------------------
                                                    2006             2007         2008 (est.)      2009 (est.)
----------------------------------------------------------------------------------------------------------------
Bioterrorism Vaccines, NIH..................            481.1            417.2            408.7            415.9
NIAID Category A Pathogen Vaccine Research..            258              200              196              200
----------------------------------------------------------------------------------------------------------------

    Question. Also, is there an entity within NIH that looks across 
Institutes to assure that research is directed at the safety of 
vaccines? If so, who is responsible for determining priorities in this 
effort?
    Answer. NIH considers vaccine safety to be an integral component of 
all vaccine research and development, there is no specific entity 
within NIH that looks across Institutes to assure that research is 
directed at the safety of vaccines. There are coordinating groups that 
collaborate on a regular basis to discuss vaccine safety and other 
related issues in the context of specific diseases or disorders. For 
example, the NIH Autism Coordinating Committee considers potential 
underlying mechanisms or triggers for autism-spectrum disorders (ASD), 
including vaccines. Recently, several NIH institutes developed a 
Program Announcement (PA) which was released August 2008 to broadly 
address important scientific questions relating to vaccine safety.
    Once in use, vaccines are monitored for safety and efficacy by the 
Food and Drug Administration (FDA) and Centers for Disease Control and 
Prevention (CDC). The Federal Government has numerous checks and 
balances in place to monitor the safety and efficacy of vaccines and to 
ensure that recommendations about immunization practices and procedures 
reflect the best available science. It is also important to note the 
key role of the National Vaccine Program Office (NVPO) within the 
Department of Health and Human Services, which has responsibility for 
coordinating and ensuring collaboration among the many Federal agencies 
involved in vaccine and immunization activities, including NIH, CDC, 
FDA, and the Department of Defense, among others. Vaccine safety is and 
will remain a top priority for the NIH.
                                 ______
                                 
            Questions Submitted by Senator Daniel K. Inouye

                            WEICKER BUILDING

    Question. Dr. Zerhouni, at my request the Congress named the NIH 
building 36 after the former Senator Lowell P. Weicker. Driving by NIH 
almost daily, I am reminded that the Lowell P. Weicker building was 
torn down. I am aware that the building was demolished to facilitate 
the Master Plan for the Bethesda campus. As the Master Plan is 
developed, is there a plan to name another NIH building after Senator 
Weicker?
    Answer. Building 36, which bore Senator Weicker's name, has been 
demolished to make way for a new research building. NIH is currently 
reviewing the status of existing facilities on our campus, including 
the naming of buildings. In light of your interest, I will keep you 
informed as we proceed with our review.

                          BEHAVIORAL RESEARCH

    Question. Dr. Zerhouni, last fiscal year, the committee included 
report language on the subject of basic behavioral research that 
stated: ``It is therefore requested that the Director submit a report 
to the committee by December 1, 2007, indicating the scientific 
leadership structure for this field within the appropriate grant-making 
Institute.'' NIH responded in April 2008 with a report titled 
``Scientific Leadership Structure for Basic Behavioral Research'' which 
reported that 12 of the Institutes fund basic behavioral research 
totaling approximately $1 billion annually. While many in the field 
dispute the accuracy of these numbers, the NIH report seems to further 
strengthen the rationale of the committee's repeated recommendations to 
NIH that scientific leadership be provided for this important area of 
research at a grant-making Institute.
    While the NIH report of April 2008 provided the committee with a 
description of the status quo, it failed to address the central 
question of the need for scientific leadership in the field at the 
appropriate grant-making Institute. At minimum and as a first step, 
would NIH agree to create a senior advisory position within NIGMS, 
which would be filled by a person with appropriate scientific 
credentials and who would provide leadership and coordination for this 
important field?
    Answer. The NIH created the Office of Behavioral and Social 
Sciences Research (OBSSR) within the NIH Office of the Director to 
provide senior advisory leadership and coordination of NIH efforts in 
these fields. Having a senior advisory position in the Office of the 
Director allows NIH to fully utilize and coordinate resources across 
all the Institutes rather than limiting it to one IC. NIGMS is actively 
supporting basic behavioral research and training. For example, NIGMS 
has recently hired an individual with a Ph.D. in sociology to help 
oversee behavioral research and training within NIGMS and coordinate 
this research with the OBSSR. NIGMS has developed a new predoctoral 
training program directed toward the interface between basic behavioral 
and biomedical research and has funded a number of new training grants 
in this area. Furthermore, NIGMS has taken the lead in supporting 
social science research on the impact of interventions in developing 
research careers; specifically, NIGMS has spearheaded two initiatives--
one directed to understanding interventions that help underrepresented 
group participate in research careers and the second (just released) 
regarding women. See http://grants1.nih.gov/grants/guide/rfa-files/RFA-
GM-09-011.html, http://www.nigms.nih.gov/Minority/Interventions.htm and 
http://www.nih.gov/news/health/jul2008/od-14.htm). Several NIGMS staff 
members are involved in these programs including the recently hired 
individual with a Ph.D. in sociology.
    Question. The Institute's statutory mandate includes basic 
behavioral research and training, and the committee has repeatedly 
stated its belief that NIGMS has a scientific mandate in this area 
because of the clear relevance of fundamental behavioral factors to a 
variety of diseases and health conditions. Will the NIH work with the 
committee to address the need for scientific leadership of this field 
at NIGMS?
    Answer. NIH will work with the committee as these basic behavioral 
research and training activities continue to develop within NIGMS and 
across NIH. NIGMS is playing an increasingly important leadership role 
in supporting basic behavioral research. For example, they have 
initiated a new predoctoral training program directed toward the basic 
behavioral-biomedical research interface and are taking the lead in 
stimulating and supporting research to include key aspects of human 
behavior in computer models of how infectious diseases spread through 
populations. They have also taken the lead in supporting social science 
research directed toward understanding the efficacy of interventions in 
promoting research careers. They are also continuing their support of 
behavioral genetics in model organisms.

                    TRANSLATION OF RESEARCH FINDINGS

    Question. Dr. Nabel, you emphasize the importance of the 
translation of research findings to the clinic and the community. What 
is NHLBI doing to help communities and physicians adopt interventions 
that have been shown to be effective, such as the Diabetes Prevention 
Program, which demonstrated the effectiveness of moderate diet and 
exercise interventions on preventing development of diabetes?
    Answer. The NHLBI translates and disseminates research findings to 
health professionals, patients, and the public in a number of ways. To 
ensure that clinicians and patients can avail themselves of the latest 
scientific knowledge in making health-care decisions, we convene expert 
panels, which include representatives from other relevant departments 
and HHS agencies including the CDC, to develop evidence-based clinical 
guidelines. Updated guidelines for asthma management and control and 
new guidelines for the diagnosis, evaluation, and management of von 
Willebrand disease, an inherited bleeding disorder, were released in 
fiscal year 2007, and the Institute is currently developing the first-
ever integrated cardiovascular risk-reduction guidelines for adults and 
children as well as updating its specific guidelines on adult 
hypertension, high blood cholesterol, and overweight/obesity.
    We also communicate research findings through community education 
programs. For example, We Can!TM promotes maintenance of a 
healthy weight in children through partnerships and media outreach 
operating in more than 500 community sites in 46 States, the District 
of Columbia, and 7 foreign countries. The sites include hospitals, 
schools, clinics, faith-based organizations, parks and recreation 
departments, extension services, YMCAs, and State health departments. 
The Institute also mounts public awareness campaigns such as The Heart 
Truth for women and heart disease, the leading cause of death among 
American women, and Learn More, Breathe Better for chronic obstructive 
pulmonary disease, the fourth most common cause of death in the United 
States.
    The NHLBI supports effectiveness studies to test interventions 
designed for easy and effective adoption in real-world settings. For 
instance, in 2006 we funded three clinical trials of strategies to 
reduce cardiovascular disease risk in obese patients who also have 
hypertension or metabolic syndrome. Although the primary emphasis is on 
developing and evaluating weight-loss programs that are effective in 
routine clinical practice, an important secondary focus is on improving 
application of evidence-based guidelines to reduce other CVD risk 
factors.
                                 ______
                                 
              Questions Submitted by Senator Patty Murray

                         NEUROLOGICAL DISEASES

    Question. Dr. Zerhouni, neurological diseases, disorders, and 
injuries affect as many as 100 million Americans--1 out of 3. In 
addition to the pain that they cause, not just to those suffering but 
to their families as well, the annual economic burden of neurological 
illness is over $1 trillion. I will look forward to working with you 
and your staff to ensure that NIH has the resources it needs to fully 
explore these important avenues of research. Would you agree that 
comprehensive, coordinated neurotechnology research should be a top 
priority for NIH?
    Answer. Finding treatments and cures for neurological diseases, 
disorders, and injuries are high priority for NIH. The NIH budget 
strongly supports neuroscience research, and programs already underway 
at NIH ensure a comprehensive, coordinated approach to developing tools 
and technologies to combat problems that affect the nervous system.
    The neuroprosthesis program, which began more than 35 years ago at 
NINDS, led to the development of cochlear implants, the first practical 
neuroprosthetic devices, which the FDA first approved in the 1980s and 
is now used by more than 100,000 people worldwide. Among its many other 
contributions, this program also made significant contributions to the 
development of deep brain stimulation (DBS), which the FDA approved for 
essential tremor and Parkinson's disease in the 1990s, and is 
continuing to improve DBS technology and expand its application to 
other diseases. More recently, advanced neuroprosthetics, including 
those directly controlled by signals from the brain, are emerging from 
this research. The NIH neuroprosthesis program, like other NIH 
neurotechnology programs, coordinates research across several NIH 
Institutes, including the newest, the National Institute of Biomedical 
Imaging and Bioengineering.
    The Neuroscience Blueprint, begun in 2004, is a cooperative 
framework among the 16 NIH Institutes, Centers and Offices that support 
neuroscience research. By pooling resources and expertise, the 
Blueprint develops tools, training opportunities, and resources to 
assist neuroscientists in both basic and clinical research. For 
example, the Blueprint currently supports the development of 
genetically manipulated mouse models and their use to map gene 
expression in the brain and to better understand brain development and 
functioning; neuroimaging studies of normal brain development and 
neuroinformatics tools to improve brain imaging techniques; and 
resources and repositories for genetic material as well as neural cell 
and tissue samples.
    Another trans-NIH mechanism, the NIH Common Fund, also supports the 
development of tools and technologies to benefit all biomedical 
research, including neuroscience. For example, NIH Roadmap initiatives 
on bioinformatics and computational biology, on interdisciplinary 
research, and on ``molecular libraries'' each support extensive 
research related to neurological problems.
    Finally, I would also like to emphasize that NIH coordinates 
neurotechnology-related activities with other Federal agencies. The 
development of neural prosthetics and better treatments for traumatic 
brain injury are two examples that are particularly important now, 
because of the injuries to people serving our country in Iraq and 
Afghanistan. In both these examples, we coordinate extensively not just 
within NIH but also with the Department of Defense, the Department of 
Veterans Affairs and other agencies through formal and informal 
contacts, interagency conferences, review panels, planning meetings, 
and support of extramural investigators for related projects.

                           PANCREATIC CANCER

    Question. Dr. John Niederhuber, given the fact that pancreatic 
cancer deaths are increasing, what concrete steps will you take to make 
this field of study a higher priority?
    Answer. NCI continues to fund research to understand the molecular 
pathways and genomic changes associated with many cancers. Similar 
genetic changes are seen in several tumor types. For example, Ras is a 
protein that under normal conditions regulates cell growth. When 
mutated it can cause uncontrollable cell growth or cancer to occur. Ras 
is associated with prostate, breast, colon, and pancreatic cancer among 
others. Further understanding Ras will help identify targets for new 
drugs and therapies for pancreatic cancer.
    In addition, NCI will continue to invest specifically in pancreatic 
cancer research. For example, NCI's major new initiatives--including 
the NCI Alliance for Nanotechnology in Cancer and the Cancer Biomedical 
Informatics Grid (caBIG)--hold a great deal of promise for improving 
and extending the lives of pancreatic cancer patients.
    These efforts have resulted in a strong infrastructure and cutting-
edge scientific research program to study all aspects of pancreatic 
cancer including prevention, early diagnosis, and therapy. It is 
expected that NCI's support of pancreatic cancer research and resulting 
science advances will continue to increase.
    Question. We've seen how important early detection tests have been 
in reducing mortality for other cancers. How far away are we from 
finding an early detection test for pancreatic cancer?
    Answer. While it is very difficult to estimate how far we are from 
a new diagnostic test, the peer-reviewed NCI-supported projects listed 
below are part of multiple NCI activities that are relevant to reaching 
that goal.
  --Commonly used imaging methods, such as endoscopic ultrasound, 
        abdominal CT scan, or MRI, are inadequate for the detection of 
        early stage pancreatic cancer. This has led to NCI's investment 
        in a portfolio that includes multiple relevant early biomarker 
        detection research projects. Sixteen early detection biomarkers 
        for pancreatic cancer are in pre-validation studies with others 
        rapidly being added to the validation pipeline.
  --CA 19-9 is presently the most widely used serum marker for 
        pancreatic cancer, but as a screening test in an asymptomatic 
        population, its positive predictive value is below 1 percent. 
        Early Detection Research Network (EDRN) investigators are 
        actively exploring both genomic and proteomic markers to 
        improve the ability to detect early stage pancreatic cancers.
  --Scientists at the University of Texas M.D. Anderson Cancer Center 
        are also taking a targeted approach to identify biomarkers for 
        early detection of pancreatic cancer by focusing on abnormal 
        genetic pathways. They have identified a number of genes that 
        are consistently differentially expressed in pancreatic cancer 
        and are examining these genes as candidate biomarkers.
    Question. How much funding would you need to find a pancreatic 
cancer early detection test?
    Answer. NCI will continue to make progress in the understanding 
pancreatic cancer and finding ways to diagnosis the disease early. The 
development of advanced technologies, new research projects, and a 
cadre of expert scientists working on the problem are critical to this 
effort. As noted above, NCI is supporting a number of early detection 
research initiatives and promising results have been realized. While it 
is impossible to say how much funding is needed to develop an early 
detection test for pancreatic cancer, investment in cancer research has 
never been more critical or more needed.
    Question. How is the NCI prioritizing this effort given that 
pancreatic cancer is one of the deadliest forms of cancer and is 
currently the fourth leading cancer killer?
    Answer. NCI recognizes the importance of pancreatic cancer research 
efforts. For example, a pancreas state-of-the-science meeting was held 
at NCI in December of 2007 to bring together investigators and other 
stakeholders to develop a research agenda for adenocarcinoma of the 
pancreas over the next 3-5 years. Based on input from the meeting, the 
Gastrointestinal Scientific Steering Committee of the NCI Clinical 
Trials Working Group (CTWG), working with cooperative groups and other 
groups that are active in pancreatic cancer clinical research, are 
developing strategic priorities for future clinical trials. Their 
recommendations will be disseminated to the relevant oncology, imaging 
and translational research communities.
    In addition, the Pancreatic Cancer Research Map (http://
www.cancermap.org/pancreatic/index.jsp) was recently developed as a 
tool for tracking pancreatic cancer research, clinical trials, and 
investigators. The map is a collaborative project between NCI, the 
Pancreatic Cancer Action Network (PanCAN), and the Lustgarten 
Foundation for Pancreatic Cancer Research. The map is designed to 
facilitate and expedite collaborations among researchers in the 
pancreatic cancer research community by helping them find related 
projects in pancreatic cancer research and network with other 
researchers, and also to identify funding opportunities specific to 
pancreatic cancer research.
    As mentioned above, NCI is also supporting major new initiatives--
including the NCI Alliance for Nanotechnology in Cancer, PanScan, and 
the Cancer Biomedical Informatics Grid (caBIG)--which have great 
potential for advancing pancreatic research.
                                 ______
                                 
              Questions Submitted by Senator Arlen Specter

                              NIH FUNDING

    Question. Dr. Zerhouni, on May 23, 2008, I wrote to you asking 
``how much would it cost to cure cancer or at least make a major 
frontal attack on the many strains of cancer?'' You responded with an 
estimate of $5.2 billion ($1.2 billion for NCI and $4 billion for the 
rest of NIH). Could you please elaborate on the need for this funding 
with respect to finding cures for cancer and other diseases?
    Answer. Despite the extraordinary progress made across all fields 
of biomedical sciences funded by the NIH in the past 50 years, we still 
do not know much of the basic biology that is needed to cure the more 
than 200 types and subtypes of cancers our patients battle daily. Much 
more work is needed to speed progress.
    As the NIH Director, I have witnessed a great acceleration in the 
pace of discoveries, many derived from the completion of the Human 
Genome Project in 2003. These discoveries provide unprecedented 
research opportunities across all disease areas. The National Cancer 
Institute (NCI) and the National Human Genome Research Institute 
(NHGRI) are currently collaborating in a Cancer Genome initiative. In 
July 2008, a pilot study by NCI and NHGRI produced new clues of genetic 
factors that play an important role in one of the most aggressive forms 
of brain cancer. Similarly, a landmark study identified new genes, and 
therefore, new leads in understanding autism, a disease of growing and 
grave concern to all of us. These are examples of the almost weekly 
reports I received of the discovery of novel factors in many diseases, 
as opposed to a few reports per year at the beginning of my tenure in 
2002.
    Given the nature of scientific discovery, any estimates about exact 
costs and timing of breakthroughs in any disease are uncertain. 
Moreover, we have seen progress in one disease often comes from 
unrelated areas of investigation, thus, we must support a wide range of 
approaches across all fields of science.
    Question. Why do you feel that the success rate for grant proposals 
should be 30 percent instead of the 18 percent currently projected?
    Answer. The success rate of 30 percent for grant proposals would 
contribute to scientific progress. We estimate the success rate of 
research applications could be 18 percent in fiscal year 2009. Young 
investigators too often become discouraged and opt for other careers, 
depleting the ranks of the next general of scientists and depriving the 
Nation of important new talent and ideas that could exploit the 
unprecedented opportunities NIH research has made possible and help 
keep our Nation competitive in this strategic area.
    Question. For all witnesses: Senator Harkin and I have introduced 
legislation providing an additional $5.2 billion to the NIH. What 
activities would you emphasize with additional funds?
    Answer. Efforts to prevent, detect, and treat disease require 
better understanding of the dynamic complexity of the many biological 
systems of the human body and their interactions with our environment 
at several scales--from atoms, molecules, cells and organs, to body and 
mind. As the questions become more complex, and even as knowledge 
grows, research itself becomes more multi-faceted. With additional 
resources above the $29.5 billion requested in the President's budget 
for NIH as proposed in your legislation, much work could be done to 
speed progress.
    These funds would allow NIH to leverage scientific opportunities in 
areas like:
  --Research Pipeline.--Additional funds will provide NIH with the 
        ability to increase its focus on the troubling trends in 
        training and research career support, which will affect the 
        pipeline of researchers for many years in the future. Examples 
        include: Training programs for pediatric diabetes researchers; 
        increased career development awards; increased trainees; 
        opportunities to train new clinical researchers; more support 
        for Malaria research training programs; increased training in 
        informatics; and expanded women's health training programs.
  --Repositories.--Additional funds would allow NIH the ability to 
        expand critical data and tissue repositories. Examples include: 
        expand tissue repositories for breast and prostate cancer; 
        expanded Human Genetics Repository; expanded support for in-
        depth analysis of data collected from whole genome association 
        studies; support for research related to the Genome-wide 
        Association Studies (GWAS) findings; and increased 
        applications/utilization of GWAS data.
  --Clinical Trials.--Additional funds would provide NIH the ability to 
        expand in the area of clinical trials research. Examples 
        include: expand the special program of translational research 
        in Acute Stroke centers; launch a study to treat children with 
        critical asthma; fund more studies in certain minority 
        populations, including Asian Americans and Native Americans; 
        support an initiative in Noise-Induced Hearing Loss; increased 
        support for the Bipolar Trials Network; and increased support 
        for Phase III trials in medications development.
  --Technologies.--Additional funds would provide NIH the ability to 
        pursue next-generation technologies that will facilitate 
        research progress. Examples include: work to increase non-
        invasive functional monitoring to improve clinical studies in 
        kidney diseases; increase investment in projects related to the 
        Brain-Computer Interface; ensure steady program in research to 
        develop the $1,000 genome; and increase NIH's ability to pursue 
        opportunities in advanced imaging and delivery technologies.
    In addition to the examples provided above, NIH could support 
nearly 1-in-3 of every application received, for a success rate of 30 
percent.
    Question. Have the flat funding levels provided to the NIH over the 
past 5 years seriously harmed the United States research enterprise?
    Answer. Within resources available, currently $29.5 billion in 
fiscal year 2008, NIH has supported the highest priority research. 
Recent budgets have reduced overall purchasing power for the biomedical 
research community and have required NIH to make tough decisions on how 
resources are allocated. The success rate for applicants receiving 
awards has declined from 30 percent in fiscal 2003 to 21 percent in 
fiscal year 2007 and an estimated 18 percent in fiscal year 2009, 
though the rapid rise in the number of applications submitted has also 
been a major factor.
    Some of the ways in which NIH has managed current resources across 
the Institutes and Centers include: reducing/delaying support for 
clinical trials; scaling back certain research training programs; data 
and tissue repositories have not been expanded as initially planned or 
have been deferred; and slowing or deferring the planning for 
developing specific computer interface, non-invasive monitoring, and 
advanced imaging and delivery technologies.
    The fiscal year 2009 request will, however, continue to move 
science forward. We will continue to invest in the best science and 
work with the community to use the resources provided to develop and 
translate scientific advances into therapies, cures, and diagnostics.
    Question. Is our international scientific pre-eminence in jeopardy 
due to these flat budgets?
    Answer. The United States is now the pre-eminent force in 
biomedical research. Our Nation continues to lead the highly 
competitive biotechnology and pharmaceutical sectors. Yet, we are also 
the focus of increasing competition from growing research in Europe and 
Asia. We must continually sustain the momentum of U.S. biomedical 
research. The table below reflects the increased rate of global 
competition.


                               STEM CELLS

    Question. Dr. Zerhouni, you have publicly stated that it is time 
for scientists to have access to more embryonic stem cell lines. Under 
your leadership, NIH funding for stem cell research has slowly but 
steadily grown and the work of the NIH stem cell unit to characterize 
the available stem cell lines has been excellent. When the ban on 
funding for additional lines is rescinded, how would you suggest the 
NIH work to realize the full potential of embryonic stem cells as 
quickly and efficiently as possible?
    Answer. NIH keeps abreast of the current policies that guide 
Federal funding of human embryonic stem cell (hESC) research. We will 
modify these policies and the eligibility criteria for Federal funding, 
including the rapid development of Guidelines, as necessary, taking 
into consideration all the information currently available. In 
addition, NIH continues to rapidly assess research needs and 
opportunities in stem cell biology and develop initiatives that meet 
those needs to capitalize on these opportunities, consistent with 
existing policies.
    Question. Dr. Nabel, a recent report in the journal Nature 
described how a laboratory was able to turn human embryonic stem cells 
into heart progenitor cells and sort them from the non-heart cells. 
Please explain why this advance is important and how stem cells may one 
day be used to treat heart disease or test prospective heart drugs.
    Answer. The investigators reporting in the journal Nature 
successfully used human embryonic stem cells to produce cardiovascular 
progenitor cells that, in turn, were able to differentiate into the 
three cell types needed to form the human heart--cardiomyocytes (to 
make the heart muscle), smooth muscle cells, and endothelial cells (to 
make blood vessels). This is an important step toward development of 
new strategies to regenerate damaged hearts.
    Heart progenitor cells have great potential for the repair of heart 
muscle injured by myocardial infarction or other cardiac diseases. 
Researchers hope that injection of the cells into patients early after 
a heart attack, either through the coronary arteries or directly into 
the muscle, could help to restore heart function and prevent the 
development of heart failure. In patients with chronic heart disease 
who have already developed heart failure, the cardiac progenitor cells 
may be able to restore the heart's ability to pump effectively.

                                 LP(A)

    Question. Dr. Nabel, is there anything new that you can tell me 
about the status of research toward a medication that lowers LPa?
    Answer. There is little evidence that lowering Lipoprotein (a) 
(Lp(a)) with specific drugs reduces cardiovascular risk. In fact, based 
on the current scientific evidence, Lp(a) measurement is not 
recommended as a screening tool for cardiovascular disease (CVD) risk 
in the general population, but only for individuals with a personal or 
family history of early-onset heart disease. At present, if an 
individual is found to have elevated levels of Lp(a), the recommended 
treatment strategy, which is supported by clinical trial evidence, is 
to aggressively lower the individual's LDL cholesterol with statins to 
decrease overall CVD risk.
    The Institute will continue to review the scientific evidence 
related to emerging CVD risk factors such as Lp(a). We are currently in 
the process of updating the Adult Treatment Panel (ATP) guidelines of 
the National Cholesterol Education Program, an evidence-based set of 
guidelines on cholesterol management published in 2001. As part of that 
effort, the expert panel developing ATP IV will evaluate the evidence 
that Lp(a) confers risk for CVD and will consider the evidence 
regarding whether Lp(a) lowering is warranted.

                            HIV/AIDS VACCINE

    Question. Dr. Fauci, you recently called for a re-evaluation of our 
efforts toward finding an HIV/AIDS vaccine. Why have we had so many 
false starts toward HIV/AIDS vaccines and how should we approach the 
problem in the future?
    Answer. There is rarely a clear pathway to developing a vaccine, 
and it is not unusual for investigational vaccines to fail. It took 
decades to develop currently licensed vaccines to combat typhoid, 
pertussis, polio, and measles. Science is iterative, and from each 
product that fails in clinical trials, we learn something that informs 
the next clinical trial.
    HIV vaccine development has been challenging for a number of 
reasons, including the fact that the virus mutates rapidly, hides from 
the immune system, and targets and destroys the immune system cells 
that are successful in fighting and clearing most other viruses from 
the body. With HIV we will have to do better than nature if we are to 
develop a vaccine, unlike the situation with other viral diseases such 
as measles and influenza, where we have succeeded in inducing 
protective responses with vaccines by mimicking the response to natural 
infection. And because of safety concerns, vaccine approaches commonly 
used to fight other infectious diseases, such as the live attenuated 
(weakened) or killed viruses used in other vaccines, are not tenable in 
HIV vaccine development.
    The failure of the Merck HIV vaccine candidate used in the STEP 
clinical trial prompted NIAID to re-evaluate our HIV vaccine research 
efforts. We initiated numerous consultative meetings with scientific 
experts and various stakeholders on how best to reinvigorate and 
advance HIV vaccine research in the wake of the STEP trial, culminating 
in an HIV vaccine summit on March 25, 2008. Those discussions revealed 
widespread consensus that the development of a safe and effective HIV 
vaccine will require significant advances in our understanding of the 
virus and an increased emphasis on basic vaccine discovery research to 
learn more about immune responses and better identify potential vaccine 
candidates while simultaneously advancing the most promising vaccine 
candidates into human clinical trials when appropriate.
    NIAID has already taken a number of steps designed to achieve a 
more appropriate balance between vaccine discovery and clinical 
development. In May 2008, we supported a new program to study the 
response of B-cells to HIV infection--a departure from previous 
efforts, which had focused on T-cell response. NIAID also began two new 
major initiatives designed to support investigator-initiated grants for 
discovery research on HIV vaccines and tactics to interrupt HIV 
transmission. We are also expanding non-human primate research to 
support HIV vaccine discovery, and improved animal models are being 
developed for use in the pre-clinical evaluation of vaccine candidates 
and to identify correlates of immunity. Lastly, NIAID created a Vaccine 
Discovery Branch in the Vaccine Research Program within the Division of 
AIDS to help build bridges between basic researchers and HIV vaccine 
designers, identify gaps in knowledge needed to develop an HIV vaccine, 
and promote research to fill those gaps.

                           GENETICS RESEARCH

    Question. Dr. Collins, the Human Genome Project was completed in 
2003. What is left to do in the area of genetics research?
    Answer. After leading the Human Genome Project to the successful 
completion of its extraordinary goal of sequencing the entire human 
genome in 2003, NHGRI expanded its mission to encompass a broad range 
of studies aimed at understanding the structure and function of the 
human genome and its role in health and disease. To that end, NHGRI 
supports the development of resources and technology that will 
accelerate genomic research and its application to human health, thus 
enabling truly pre-emptive, predictive, personalized, and participatory 
health care.
    Question. What practical medical benefits have been achieved and 
what will soon be available?
    Answer. The Human Genome Project has led to important discoveries 
related to genetic predisposition to some of the most common causes of 
morbidity and mortality in the United States today. These discoveries 
can lead to improved diagnostic, therapeutic, and pre-emptive 
approaches. Examples are listed below.
  --Type 2 Diabetes.--Nearly 20 new genetic markers have been 
        discovered to be associated with type 2 diabetes. For example, 
        homozygosity--that is, having two identical forms of a gene--or 
        TCF7L2 gene mutations has been shown to convey a 140 percent 
        increased risk of type 2 diabetes.
  --Heart Disease.--Multiple new markers associated with coronary heart 
        disease have been discovered. For example, homozygosity for a 
        variant on chromosome 9p21--as occurs in approximately 25 
        percent of people of European ancestry--increases risk for 
        coronary artery disease by an estimated 60 percent.
  --Breast Cancer.--A number of genetic markers are now known to affect 
        risk for developing breast cancer. Recently-discovered 
        variations in the FGFR2 and CASP8 genes are associated with a 
        13-26 percent increase in risk of developing breast cancer.
  --Prostate Cancer.--Variations in several genes on chromosome 8 have 
        been shown to be associated with 30-50 percent increase in the 
        risk of prostate cancer.
  --Age-Related Macular Degeneration (AMD).--Five genes have been found 
        to account for over 70 percent of the incidence of age-related 
        macular degeneration, which is the leading cause of severe 
        vision loss in older Americans. Each of these genes is 
        associated with a 30-160 percent increased risk of AMD.
    The Human Genome Project has led to improved diagnostic testing, 
with diagnostics now available for more than 1,300 genetic disorders, 
and also to improved prognostic testing, such as microarray-based 
assays like MammaPrint and Oncotype DX that predict breast cancer 
recurrence and guide treatment options.
    The HGP has also led to the rapid development of pharmacogenomics, 
giving physicians the ability to prescribe a wide range of medications 
more safely. For example, a recent study has shown that HLA-B*5701 
testing effectively predicts potentially severe adverse reactions to 
the HIV medicine abacavir.
    Susceptibility to disease is only part of the picture. The HGP has 
also enabled development of many new drugs targeted at diseases such as 
age-related macular degeneration, myocardial infarction, and melanoma. 
In addition, the NIH Roadmap project on Molecular Libraries enables 
direct translation from gene discovery to treatment by finding new uses 
for pre-existing drugs and identifying small molecule, drug-like 
compounds that can serve as starting points for new treatments. For 
example, this approach was recently used by the NIH Chemical Genomics 
Center (NCGC) to identify a potential new treatment against the 
parasitic disease, schistosomiasis, which affects upwards of 200 
million people in the developing world, causing an estimated 280,000 
deaths annually.

                                 CANCER

    Question. Dr. Niederhuber, what is your projection on when cancer--
or many cancers--will be treatable or curable? Also, in a response to a 
question from me, the cancer community has indicated that $335 billion 
over the next 15 years is necessary to make real progress toward cancer 
cures. What do you think is necessary in terms of time, funding, and 
research breakthroughs to make a real difference in curing cancer?
    Answer. Cancer, as you know, is not just one disease. It is perhaps 
as many as 1,000 different diseases, and as such it is a very complex 
and dynamic process. Unfortunately, I can't give you a timeframe for 
how long it will take to cure cancer or make it much more than a 
chronic set of diseases that we can prevent or live with. However, 
we're learning and understanding more and more every day, and we are 
gaining vital new knowledge that will get us closer to our goal.
    As the leader of the National Cancer Program, NCI is, today, 
building on its history of research success and wisely spending every 
dollar it receives, in a continual effort to foster the best research 
and to connect the public, private, and academic sectors for effective 
translation of these discoveries. If NCI were to receive the increase 
of $1.2 billion identified in the fiscal year 2009 by-pass budget, then 
NCI could better lead these collaborations and connectivity--to shorten 
the path from an innovative discovery in the laboratory to making an 
effective difference with a patient in the clinic. Listed below are 
some potential investments:
  --Increase the number of new investigators;
  --Expand research training opportunities;
  --Rebuild scientific infrastructure;
  --Expand caBIG;
  --Raise RPG success rate and average cost per grant;
  --Expand Cancer Centers program;
  --Invest in intramural program;
  --Expand The Cancer Genome Atlas;
  --Increase Drug Development;
  --Re-engineer Clinical Trials;
  --Fund early phase pharmacodynamic studies;
  --Create a U.S. oncology tissue bank;
  --Establish certified centralized tumor characterization labs;
  --Enhance technological efforts around nanoparticles and proteins;
  --Enhance technology development in clinical proteomics;
  --Invest in systems biology;
  --Increase biomedical computing capabilities; and
  --Develop imaging tools.
    To effectively operationalize this plan would require that we build 
scientific capacity. We must maximize our efforts to recruit and 
sustain the very best and brightest to work on cancer. As in the past, 
an investment in understanding the complex systems involved in cancer 
initiation and growth will continue to impact our understanding and 
treatment of all diseases--acute and chronic.

                         CONCLUSION OF HEARINGS

    Senator Harkin. So, thank you all very much, that concludes 
our hearings.
    [Whereupon, at 11:56 a.m., Wednesday, July 16, the hearings 
were concluded, and the subcommittee was recessed, to 
reconvenue subject to the call of the Chair.]
