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[Senate Hearing 111-271]
[From the U.S. Government Publishing Office]

                                                        S. Hrg. 111-271

              CANCER RESEARCH: FUNDING INNOVATIVE RESEARCH

=======================================================================

                                HEARING

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                     ONE HUNDRED ELEVENTH CONGRESS

                             FIRST SESSION

                               __________

                            SPECIAL HEARING

                     JULY 6, 2009--PHILADELPHIA, PA

                               __________

         Printed for the use of the Committee on Appropriations

  Available via the World Wide Web: http://www.gpoaccess.gov/congress/
                               index.html
                               __________

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                      COMMITTEE ON APPROPRIATIONS

                   DANIEL K. INOUYE, Hawaii, Chairman
ROBERT C. BYRD, West Virginia        THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont            CHRISTOPHER S. BOND, Missouri
TOM HARKIN, Iowa                     MITCH McCONNELL, Kentucky
BARBARA A. MIKULSKI, Maryland        RICHARD C. SHELBY, Alabama
HERB KOHL, Wisconsin                 JUDD GREGG, New Hampshire
PATTY MURRAY, Washington             ROBERT F. BENNETT, Utah
BYRON L. DORGAN, North Dakota        KAY BAILEY HUTCHISON, Texas
DIANNE FEINSTEIN, California         SAM BROWNBACK, Kansas
RICHARD J. DURBIN, Illinois          LAMAR ALEXANDER, Tennessee
TIM JOHNSON, South Dakota            SUSAN COLLINS, Maine
MARY L. LANDRIEU, Louisiana          GEORGE V. VOINOVICH, Ohio
JACK REED, Rhode Island              LISA MURKOWSKI, Alaska
FRANK R. LAUTENBERG, New Jersey
BEN NELSON, Nebraska
MARK PRYOR, Arkansas
JON TESTER, Montana
ARLEN SPECTER, Pennsylvania

                    Charles J. Houy, Staff Director
                  Bruce Evans, Minority Staff Director
                                 ------                                

   Subcommittee on Departments of Labor, Health and Human Services, 
                    Education, and Related Agencies

                       TOM HARKIN, Iowa, Chairman
DANIEL K. INOUYE, Hawaii             THAD COCHRAN, Mississippi
HERB KOHL, Wisconsin                 JUDD GREGG, New Hampshire
PATTY MURRAY, Washington             KAY BAILEY HUTCHISON, Texas
MARY L. LANDRIEU, Louisiana          RICHARD C. SHELBY, Alabama
RICHARD J. DURBIN, Illinois          LAMAR ALEXANDER, Tennessee
JACK REED, Rhode Island
MARK PRYOR, Arkansas
ARLEN SPECTER, Pennsylvania
                           Professional Staff

                              Ellen Murray
                              Erik Fatemi
                              Mark Laisch
                            Adrienne Hallett
                             Lisa Bernhardt
                       Bettilou Taylor (Minority)
                        Dale Cabaniss (Minority)
                      Sara Love Swaney (Minority)

                         Administrative Support

                              Teri Curtin
                         Jeff Kratz (Minority)

                            C O N T E N T S

                              ----------                              
                                                                   Page

Opening Statement of Senator Arlen Specter.......................     1
Statement of Dr. Lawrence A. Tabak, D.D.S, Ph.D., Acting 
  Principal Deputy Director, National Institutes of Health, 
  Bethesda, Maryland.............................................     3
    Prepared Statement of........................................     4
Statement of Dr. Richard G. Pestell, M.D., Ph.D., Director, 
  Kimmel Cancer Center, Thomas Jefferson University, 
  Philadelphia, Pennsylvania.....................................    10
    Prepared Statement of........................................    12
Statement of Dr. Michael V. Seiden, President and CEO, Fox Chase 
  Cancer Center, Philadelphia, Pennsylvania......................    14
    Prepared Statement of........................................    16
Statement of Dr. Craig B. Thompson, M.D., Director, Abramson 
  Cancer Center, University of Pennsylvania, Philadelphia, 
  Pennsylvania...................................................    17
    Prepared Statement of........................................    19
Statement of Dr. Eileen K. Jaffe, Adjunct Professor, University 
  of Pennsylvania, Fox Chase Cancer Center, Philadelphia, 
  Pennsylvania...................................................    20
    Prepared Statement of........................................    22
Statement of Dr. Thomas Curran, Ph.D., Deputy Scientific 
  Director, Stokes Research Institute, Children's Hospital of 
  Philadelphia, Phialdelphia, Pennsylvania.......................    24
    Prepared Statement of........................................    25
Statement of Dr. Russel E. Kaufman, President and CEO, The Wistar 
  Institute, Philadelphia, Pennsylvania..........................    27
    Prepared Statement of........................................    29

 
              CANCER RESEARCH: FUNDING INNOVATIVE RESEARCH

                              ----------                              

                          MONDAY, JULY 6, 2009

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                  Philadelphia, PA.
    The subcommittee met at 9:30 a.m., in the Kirby Auditorium, 
National Constitution Center, 6th and Arch Streets, 
Philadelphia, Pennsylvania, Hon. Arlen Specter, presiding.
    Present: Senator Specter.

               opening statement of senator arlen specter

    Senator Specter. Good morning. Ladies and gentlemen, the 
time of 9:30 a.m. having arrived, the Subcommittee on Labor, 
Health and Human Services, and Education, and related agencies 
will now proceed.
    I'll begin by thanking Chairman Inouye of the full 
committee and Senator Harkin, chairman of the subcommittee, for 
authorizing this hearing.
    The purpose is to explore the standards used by the 
National Institutes of Health (NIH) for awarding grants.
    NIH has been described as the crown jewel of the Federal 
Government and some say it is the only jewel of the Federal 
Government.
    NIH has produced some remarkable scientific advances. 
Really, with the research techniques available and the 
availability now of stem cells; especially embryonic stem 
cells, which can replace disease cells, it's practically the 
Fountain of Youth.
    The funding for NIH has increased dramatically in the 
course of the past two decades.
    When I chaired the subcommittee for a decade with the 
concurrence of Senator Harkin, who was then ranking minority 
member, the funding was increased from $12 to $30 million; on 
the stimulus package enacted earlier this year, on my 
amendment, an additional $10 billion was added to the funding.
    In sub-years during the 1990's, and the early part of the 
2000 decade, funding increased as much as $3 to $3.5 million 
and there was a great upsurge in the allocated grants.
    That had slowed, with the budget crunch, and across the 
board, and failure to have cost-of-living adjustments, which 
had met a decline in recent years of some $5 billion.
    The $10 billion allocation from the stimulus package has 
created a wave of excitement with the availability of 15,000 
grants. It's a real job producer; 70,000 high-paying jobs in a 
2-year period.
    The administration's proposal, this year, is to have an 
increase in NIH funding of $443 million, which is totally 
insufficient. Doesn't even keep up with the cost-of-living 
increase and some of that minimal funding has been attributed 
to the stimulus package, but the stimulus package was not 
designed to substitute for annual funding.
    Today's hearing is partially in response to an article in 
the New York Times, 1 week ago, yesterday; which raises very 
significant questions about the grants which were allocated, 
whether they are on-target. Comments which were made by a 
distinguished oncologist, Dr. Robert Young, the Chancellor at 
the Fox Chase Cancer Center in Philadelphia, pointed out that 
the grants are very conservative, only likely to produce 
incremental progress, and with this kind of an approach, there 
may be a major difference in cancer prevention and treatment 
when transformational kind of grants are crowded out.
    The comments go on to illustrate quite a number of 
situations where grants with really great potential for 
innovation have been rejected, because they are uncertain.
    The point is made that if they could be proved and 
established you wouldn't have to have the grants.
    One of the applicants is a distinguished research scientist 
from Fox Chase, Dr. Ellen Jaffe, who has published research; a 
respected established researcher, but when she had some ideas 
for a very dramatic kind of research they were rejected out of 
the conservative approach of the National Institutes of Health.
    We have a very, very distinguished panel today; experts 
from major cancer institutes in this area.
    You couldn't find a better place to hold a hearing of this 
sort then in Philadelphia with the pre-eminent scientists and 
oncologists in the field.
    One of our witnesses today is Dr. Craig Thompson from the 
hospital of the University of Pennsylvania. Dr. Thompson is the 
Director of the University of Pennsylvania's Abramson Cancer 
Center and he is the John H. Glick Professor of Medicine and 
Biology.
    These Chairs are named for renowned people and just a 
personal comment about Dr. Glick; he's my doctor.
    As is known, I've had a couple of bouts with Hodgkin's, and 
have had a couple of responses with chemotherapy. A pretty 
tough regimen and Dr. Glick has been my doctor. So, it's 
interesting to see a Chair named after your doctor. I think 
that would be done some time in the distant future when he was 
no longer on the scene, but Dr. Glick has moved upstairs, and 
still treats a great many patients. Has a very remarkable 
practice.
    One attribute, that I shall mention, is the way he answers 
the phone. He carries his cell phone with him. Something I 
could never manage to do and on the first ring, John Glick. I 
make a fair number of calls. I've never heard such prompt 
responses. It isn't average. It isn't 5 out of 6 or 19 out of 
20. He seldom misses.
    I had a very deep concern about NIH long before I had my 
own personal problems, but as you might have imagined, they 
have been intensified when it is personal.
    We now turn to our first witness, Dr. Lawrence Tabak. He is 
the Acting Principal Deputy Director at NIH, as well as the 
Director of the NIH Institute of Dental Research. He has an 
undergraduate degree from the City College of New York, a 
Doctor of Dental Science degree from Columbia, and a Ph.D. from 
the State University of New York.
    We appreciate you coming from Washington today, Dr. Tabak.
    In accordance with the subcommittee rules, we ask that your 
testimony be limited to 5 minutes.
    Please proceed.
STATEMENT OF DR. LAWRENCE A. TABAK, D.D.S, Ph.D., 
            ACTING PRINCIPAL DEPUTY DIRECTOR, NATIONAL 
            INSTITUTES OF HEALTH, BETHESDA, MARYLAND
    Dr. Tabak. Good morning Mr. Chairman. It's my pleasure to 
testify before you today on NIH's efforts to fund additional 
innovative research.
    I've submitted my testimony for the record and I'll use 
this allotted time to just summarize key points.
    Senator Specter. Thank you.
    Dr. Tabak. Innovation, transformation, and impact are 
notoriously more difficult to recognize prospectively, then 
retrospectively. Still these challenges do not reduce our 
responsibility to aggressively engage the issue of supporting 
research that has the greatest potential impact. With this in 
mind, I'd like to highlight several areas that NIH is engaged 
in to strengthen our support for a more innovative and high-
impact research.
    In 2007, NIH launched a comprehensive effort to enhance our 
peer-review system and make it more sensitive to both the 
impact and the innovation of the proposed work. After receiving 
extensive national input, we worked to implement cost 
strategies that emerged and, in fact, reviewers for the 
applications of the recent Challenge Grant and Grant 
Opportunity Programs, to be funded by the American Recovery and 
Reinvestment Act, have used a new review process that emerged 
with a scoring system that emphasizes the potential impact and 
risk of the proposed projects.
    Another effort to support innovation comes from the NIH 
Road Map for Medical Research and the Common Fund. It supports 
transformative high-impact research that expands beyond the 
traditional boundaries and holds significant promise for 
improving the public's health. Road Map acts as an incubator 
space for these new ideas and approaches and though it is still 
relatively new, it has produced initial results so promising 
that the Congress provided a legal foundation for an NIH Common 
Fund supporting these efforts through the passage of the 2006 
Reform Act.
    Though the Common Fund has many facets, let me focus on 
three programs designed, specifically, to support innovation 
and its researchers and projects.
    The first are the NIH Director's Pioneer Award Program. 
This is a high-risk research initiative that supports 
individual scientists of exceptional creativity, who propose 
pioneering and possibly, transforming work.
    Second, The New Innovator Award Program, which targets 
similarly creative investigators, but are at an earlier stage 
in their career, and then third, and complimenting these 
programs is the Transformative RO1 Research Program, the so-
called ``T-RO1,'' which will support transformative projects 
proposed by individual scientists or collaborative teams.
    Given your particular interest in cancer research, let me 
highlight a couple of the many highly innovative programs 
supported by the National Cancer Institute (NCI).
    Forthcoming, are new physical science oncology centers 
where physicists, chemists, mathematicians, and biologists will 
work collaboratively to form new perspectives on the physical 
forces involved in cancer.
    Twenty years ago, many questioned the decision to make so 
vast an investment in the Human Genome Project, an effort that 
could not guarantee that its knowledge would lead to immediate 
medical applications; however, recent Genome Wide Association 
Studies are helping to reveal the genetic roots of a rapidly 
expanding of array of diseases, such as cancer.
    The NIH has examined and strengthened its support for 
innovation amongst scientists across all career stages and for 
scientific projects from laboratory to clinic to community. We 
have sought ways to remove the roadblocks that have hindered 
into disciplinary cooperation and the exploration of 
unconventional leads.
    From the Common Fund in its program through initiative 
taken by NIH institutes and centers, and from our enhanced 
approach to peer review, we are already discovering unexpected 
connections between and among disciplines, diseases, and 
biological processes.

                           prepared statement

    To conclude, in our support for innovation, we must not 
lose sight of the importance of what Thomas Kuhn, who 
popularized the concept of ``paradigm shifts,'' termed 
``normal'' science. He emphasized that both normal or 
evolutionary research and revolutionary research are essential 
to improve our efforts to improve human health.
    This concludes my testimony, Mr. Chairman, and I would be 
pleased to answer any questions you may have.
    Senator Specter. Well, Doctor, your full statement will be 
made a part of the record.
    [The statement follows:]
                Prepared Statement of Lawrence A. Tabak
    Good morning, Mr. Chairman. I am Dr. Lawrence Tabak, Acting Deputy 
Director of the National Institutes of Health (NIH), and Director of 
NIH's National Institute of Dental and Craniofacial Research. It is my 
pleasure to testify before you today on the NIH's efforts to fund 
innovative research, in biomedicine generally and in cancer research 
particularly.
    Shortly after WWII, the cornerstones of NIH--its peer-review 
process and its scientific and public advisory structure--were set in 
place. Our current grants program, refined through an ongoing iterative 
process that reflects the changing demands of science and society, 
continues to rest on this foundation. Much admired and often imitated 
throughout the world, the NIH peer-review process has produced 
impressive results. These results have been widely documented, most 
recently by Kenneth Manton and his colleagues in their study of the 
longitudinal correlation of investment in NIH research with a 
significant decline in mortality in four major chronic diseases. The 
NIH's grant process has allowed the Agency to fulfill its mission of 
seeking scientific knowledge to improve the public's health.
    Given the rapidity of scientific progress and the remarkable 
technology that we have available, we know that we must continue to 
enhance our support for potentially innovative, high-impact research. 
There is a tension inherent in our grant-making process. Given finite 
resources, how do we balance support for projects that promise more 
certain results with those that are riskier, but hold the possibility 
of greater reward? ``Innovation'', ``transformation'', and ``impact'' 
are notoriously more difficult to recognize prospectively than 
retrospectively. These challenges do not reduce our responsibility to 
aggressively engage the issue of supporting the research that has the 
greatest potential impact.
              current nih support for innovative research
    Let me highlight several areas that NIH is engaged in to strengthen 
our support for more innovative and high impact research. In June 2007, 
NIH launched a comprehensive effort to enhance our peer-review system 
and make it more sensitive to both the impact and innovation of the 
proposed work. Extensive input was sought and received from a wide 
range of stakeholders across the country, which led to a comprehensive 
report released in February 2008 detailing the challenges facing our 
current system, and proposals for improvement. Four interrelated core 
strategies emerged to enhance our system of peer review: (1) engage the 
best reviewers; (2) improve the quality and transparency of reviews 
with a greater focus on scientific impact; (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.
    A new review process and a new scoring system has been implemented 
and was employed for the recent Challenge Grant and Grand Opportunity 
ARRA programs. Reviewers will provide an overall impact score to 
reflect their assessment of the likelihood for the project to exert a 
sustained, powerful influence on the research field(s) involved, in 
consideration of five core review criteria: significance, 
investigator(s), innovation, approach, and environment. Under the 
approach criterion, specific consideration is given to the level of 
risk. The scoring system will be changed completely to modify previous 
patterns of review.
    The NIH Roadmap for Medical Research was introduced by former NIH 
Director, Dr. Elias Zerhouni in 2003. The intent of the Roadmap was to 
support transformative, high-impact research that expands beyond the 
boundaries of any single NIH Institute or Center and holds significant 
promise for improving the public's health. Congress provided a legal 
authority for an NIH Common Fund, which institutionalized the Roadmap 
concept within the NIH Reform Act of 2006 (Public Law 109-482). The 
Common Fund acts as an incubator space in which new ideas and 
approaches can be tested, developed, and, ultimately, moved out of the 
Common Fund and into the larger biomedical research community.
    Though the Common Fund has many facets, I will focus on three of 
its programs that specifically support innovative researchers and 
projects. The NIH Director's Pioneer Award Program, first announced in 
2004, is a high-risk research initiative designed to support individual 
scientists of exceptional creativity who propose pioneering--and 
possibly transforming--approaches to major challenges in biomedical and 
behavioral research. To date, there have been 47 awardees; and already, 
their work is producing impressive, potentially transformative, 
results. For example, in what has turned out to be quite timely 
research, a Pioneer awardee is employing antigenic cartography to map 
differences in seasonal influenza strains worldwide. This knowledge 
should significantly improve our ability to track the influenza virus 
and select proper strains for vaccine preparation. The New Innovator 
Award Program is targeted to highly creative investigators who are 
earlier in their careers and who have the potential to produce 
solutions for broad, important problems in biomedical and behavioral 
research.
    Complementing the Pioneer and New Innovator Programs is the 
Transformative R01 Research Projects Program (T-R01), which will 
provide support for transformative projects that individual scientists 
or collaborative investigative teams propose. The program is 
specifically designed to support exceptionally innovative, high risk, 
original and/or unconventional research with the potential to create 
new or challenge existing scientific paradigms. Applications for this 
new program were recently reviewed with a two-stage process. About 100 
of 700 of the applications received met the threshold for 
transformation potential to be considered further for support. 
Applications making this initial cut where then carefully reviewed by a 
very experienced panel of scientific notables and final funding 
decisions are to be made during this fiscal year.
                           cancer initiatives
    Given your particular interest in cancer research, I will highlight 
several of many highly innovative programs supported by the National 
Cancer Institute (NCI). Forthcoming are new Physical Science-Oncology 
Centers where physicists, chemists, mathematicians and biologists will 
work collaboratively to develop new perspectives on the physical forces 
involved in cancer. Initial competing awards will be funded with fiscal 
year 2009 appropriated funds; the plan is to fund administrative 
supplements to the parent grant with ARRA dollars. Remarkably, 7 Nobel 
laureates either applied for or participated in the review of this 
exciting new program, together with 24 members of the National Academy 
of Sciences and 9 National Academy of Engineering members who were 
included among the groups that applied for this opportunity. This is 
clearly not business as usual.
    Many questioned the decision to invest so many international 
resources in the human genome project--an effort that could not 
guarantee that its knowledge would lead to immediate medical 
applications. Recently, however, Genome Wide Association Studies are 
helping to reveal the genetic roots of a rapidly expanding array of 
diseases. NCI's Cancer Genome Atlas Project recently announced 
(September 2008) the first results of its large-scale, comprehensive 
study of the most common form of brain cancer, glioblastoma. The team 
discovered new genetic mutations and other types of DNA alterations 
with potential implications for the diagnosis and treatment of 
glioblastoma.
    NCI also has invested in innovative research into biomarkers--
molecules found in the body that can signal an abnormal process or 
disease, and can be meaningful in understanding the presence of disease 
or response to treatment. In 2006, NCI, the U.S. Food and Drug 
Administration (FDA), and the Centers for Medicare and Medicaid 
Services collaborated to form the Oncology Biomarkers Qualification 
Initiative (OBQI). OBQI was designed to qualify biomarkers for use in 
clinical trials and, ultimately, to speed better agents to cancer 
patients. For example, researchers are assessing the use of positron 
emission tomography (PET) to detect fluorodeoxyglucose (FDG), a 
potential biomarker in nonsmall cell lung cancer and non-Hodgkin's 
lymphoma clinical trials. FDG-PET is an imaging test that uses a 
radioactive sugar molecule to produce images that show the metabolic 
activity of tissues. In FDG-PET scanning, the high consumption of the 
sugar by cancer cells--as compared to the lower consumption by normal 
surrounding tissues--identifies these cells as cancer. FDG's presence 
can be detected by PET imaging in tumors as small as one centimeter. 
FDG-PET clinical trials could have significant impact on patient 
management by validating a tool that can identify response to treatment 
and help facilitate new drug development.
                               conclusion
    Thomas Kuhn, the pioneering American intellectual who popularized 
the concept of ``paradigm shifts,'' underscored the importance of what 
he called ``normal'' science in determining the consequences of 
revolutionary discoveries. Both revolutionary and evolutionary research 
is essential in our efforts to improve human health. Not long ago, 
vaccines against cancer seemed an unlikely development. Then, 
scientists at the NCI 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 that cause the 
majority of cervical cancers in women. The vaccine, made by Merck & 
Co., Inc., is based on laboratory research and technology developed at 
the NCI. NCI played a pivotal role in what holds promise to be a major 
public health success story. Worldwide use of this vaccine could save 
the lives of 200,000 women each year.
    NIH has examined, and strengthened, its support for innovation: 
among scientists across all career stages; and for scientific research 
projects from laboratory to clinic to community. We have sought out 
ways to remove the roadblocks that have hindered interdisciplinary 
cooperation and the exploration of unconventional leads. Through the 
Common Fund and its programs; through initiatives undertaken by NIH 
Institutes and Centers; and, as early studies suggest, from our 
enhanced approach to peer review, we are already discovering unexpected 
connections between disciplines, diseases, and biological processes.
    NIH continues to enhance its ability to identify and support 
innovative and high-impact research through the creation of 
experimental spaces for testing new ideas; the introduction of novel 
programs; and the invention of new approaches to assess results. 
Supporting innovative research and pioneering researchers is a top NIH 
priority. If NIH is to continue along this path, NIH's stakeholders--
the whole of the Nation, and researchers around the world--must 
themselves embrace a new paradigm. If we agree to accept more risk, we 
must also accept more risk of failure. To do otherwise is to hinder 
innovation. As Elias Zerhouni often noted, ``The best way to ensure 
failure in science is to try to ensure success.'' Therefore, we must 
identify the amount of risk that is acceptable and in that context 
balance NIH's research portfolio to support an optimal balance of 
innovative and evolutionary research.
    This concludes my statement, Mr. Chairman. I will be happy to 
answer any questions you may have.

    Senator Specter. You talk about undertaking high-risk 
projects. The information in the New York Times article pointed 
out that on the category of Pioneer Awards only 3 to 5 percent 
of the applicants get funded. The fund set aside for 
Transformative R01 Grants was only $25 million. Are those 
figures accurate?
    Dr. Tabak. The success rate of Pioneer Awards is low by 
design. Only the most transformative projects meet the high bar 
that is required.
    Senator Specter. When you say that ``Only the most 
transformative projects,'' what do you mean by that?
    Dr. Tabak. These are projects that have the potential of 
changing existing paradigm within science. These are not 
projects that will add to a previously existing paradigm. These 
are projects that will take us into an entirely new direction.
    Senator Specter. Is it true that only $25 million has been 
allocated for the RO1 item?
    Dr. Tabak. In fiscal year 2009, the transformative RO1's 
were allocated through the Common Fund of up to $35 million.
    In fiscal year 2010, this is scheduled to double. This is 
up to, again, depending upon the quality of the applications 
received.
    Senator Specter. What percentage is that of $30 billion?
    Dr. Tabak. Well, obviously, a very small percentage, 
Senator.
    Senator Specter. Well, isn't that really unreasonably low 
when you are looking for innovative approaches?
    Dr. Tabak. In any application to the NIH there are, as you 
know, sir, three components. There is the application itself 
submitted by the applicant. There is the peer-review process 
that the application must go through, and finally, there is 
staff considerations taking into account and inform by the 
peer-review process. So, all three of these parts would be 
required to come to agreement that, in fact, something is 
transformative or innovative in nature.
    Senator Specter. Well, Dr. Tabak, aside from the criteria, 
if you only have $35 million, that doesn't go very far when 
you're looking at allocation by the Congress of $30 billion, 
plus $10 billion more.
    Dr. Richard Klausner, a very distinguished former director 
of the National Cancer Institute said this, ``There is no 
conversation that I have ever had about the grant system that 
doesn't have an incredible sense of consensus that it is not 
working. That is a terrible wasted opportunity of scientists, 
patients, and nations and the world.''
    Do you disagree with that?
    Dr. Tabak. Sir, we do not have a set amount of research 
that we intend to fund that comes under the Innovative or 
Transformative heading. Investigators are surely encouraged to 
submit their most innovative and creative proposals. I think 
that part of the understanding that came with the review of the 
peer-review process is that elements of it demonstrated a 
conservative aspect, if you will. This is why in the changes 
that we have proposed and have begun implementing in the peer-
review process, we think that we will be able to ensure that a 
higher emphasis is placed on things like impact, rather than 
the fine methodological detail that, perhaps, dominated the 
review process in the past.
    Senator Specter. Dr. Tabak, that sounds great, but isn't it 
really a matter of how many dollars are allocated to these high 
risk transformative processes?
    This is what Dr. Robert Young, Chancellor at Fox Chase 
said. ``The grants that are made are only likely to produce 
incremental progress, the ones which are crowded out or 
applications that could make a major difference in cancer 
prevention and treatment.''
    Do you disagree with that?
    Dr. Tabak. The process that we use, sir, which, you well 
know, is peer review and so if in the judgment of the peers a 
particular work is or is not transformative, this plays a major 
role in determining whether or not NIH will support an 
application.
    Senator Specter. But what are the standards used by the 
peers?
    Dr. Tabak. So in the past, as you know, sir, there was a 
series of criterion which, unfortunately, did not in our view, 
and in the view of many that we spoke to around the country, 
appropriately emphasize things like the overall potential 
impact of the proposed work. This is why we have enhanced the 
peer-review system to include this very important principle. 
What we have found in past programs such as the Pioneer Award 
and, subsequently, with the New Innovator Award are upon 
release of these new types of programs. It takes a bit of time 
for the community; that is, both applicants and reviewers 
alike, to re-equilibrate to a new standard of excellence.
    Senator Specter. Well, is there an effort made to a new 
standard?
    Dr. Tabak. Indeed, and so this is why you will see that the 
number of Pioneer Awards have increased each year since the 
inception of the program. That's why we hope that we will be 
able to increase significantly the number of Transformative 
RO1's, because as the community, both applicants and reviewers 
alike, adjust to what is expected it allows for us to support 
applications of this type.
    Senator Specter. Dr. Tabak, there is a view that the 
Congress had not become involved in the decisions made by the 
National Institutes of Health on a scientific basis. There is a 
concern about politicizing the process. Members of the House 
and Senate are really not equipped to do that, and we're about 
to hear from very distinguished research scientists on this 
subject. The reality is that you are on the spot a little bit 
in responding to the New York Times article and you're a 
volunteer, and you're not responsible for setting this policy. 
But I know you will listen closely to what the witnesses will 
say and it's my request on behalf of the Appropriations 
Committee for you to go back and take a look at what you will 
hear today, because I think you are going to find some very 
strong criticism of the NIH policy.
    We are searching for cures. My own instinct is that most of 
the maladies of the world can be cured if we put sufficient 
resources into the National Institutes of Health and that it is 
scandalous that more has not been done since war was declared 
on cancer in 1970.
    The subcommittee has asked NIH for a projection for what it 
would cost to cure cancer. When I say, ``cure cancer,'' I'm 
going to ask you what the realty is considering the many 
strains of cancer. Be able to figure, $335 billion over 15 
years and at a time when we're considering comprehensive health 
reform, this is a front-burner subject, which is the reason why 
we moved as fast as we did to have this hearing.
    We expect to take up comprehensive health review this week 
and for the balance of the month. So, it is very timely to make 
an evaluation as to what we're dealing with here.
    When a comment is made about curing cancer, is that 
realistic Dr. Tabak?
    Dr. Tabak. I can't predict when all cancers can be cured, 
sir. As you surely know, cancer is not a single-disease entity, 
but in fact, many disease entities. I would really not be able 
to make that type of prediction.
    Senator Specter. Well, how about a prediction on Hodgkin's?
    Dr. Tabak. Sir, again----
    Senator Specter. Too personal?
    Dr. Tabak. Again, sir, part of the reason that it is so 
difficult to predict is as we learn more and more about human 
biology, we never know where the next breakthrough comes. It 
sometimes comes from places that we never would have 
anticipated.
    Senator Specter. Do you think there is the capacity with 
our research ingenuity to pretty much eradicate the radical 
maladies of the world, with sufficient dollars for research?
    Dr. Tabak. I think with appropriate time, yes, sir, because 
we have already enjoyed so much success in eradicating a subset 
of diseases and conditions.
    Senator Specter. Well, let me ask you to undertake the very 
difficult question of a judgment on how much time and how much 
money it would take? Because at a time when we are looking at 
comprehensive health reform, you couldn't find a better time to 
come to the Congress and say, this is what we might do on 
cancer, what we might do on heart disease, on autism, on 
Parkinson's, on juvenile diabetes, on Alzheimer's.
    Dr. Tabak, I would appreciate it if you would stay for our 
panel because we may have some follow-up questions as a result 
of what they testify to.
    Dr. Tabak. My pleasure, sir.
    Senator Specter. Thank you again for coming from 
Washington.
    We will now call our panel of Dr. Pestell, Dr. Jaffe, Dr. 
Thompson, Dr. Curran, Dr. Kaufman, and Dr. Seiden.
    Thank you all for joining us.
    I have some reluctance to see cancer treatment slowed up by 
the presence of you six distinguished scientists here this 
morning, so I will try not to keep you too long. But I do think 
it is very important to hear your views and try to give us some 
guidance as to what we ought to be doing.
    We appreciate what you have done and Congress is very 
anxious to support you and make the most generous allocations 
that we can to the National Institutes of Health, and to the 
extent that we can realistically, hold out the prospect of 
curing these maladies. There is a lot of interest in doing so.
    Our first witness is going to be Dr. Richard Pestell, 
Director of the Kimmel Center at Jefferson. He is the principal 
investigator of the Institute and designated cancer center, 
M.D. and Ph.D. from the University of Melbourne in Australia.
    Thank you for joining us Dr. Pestell and the floor is 
yours.
STATEMENT OF DR. RICHARD G. PESTELL, M.D., PH.D., 
            DIRECTOR, KIMMEL CANCER CENTER, THOMAS 
            JEFFERSON UNIVERSITY, PHILADELPHIA, 
            PENNSYLVANIA
    Dr. Pestell. Good morning Senator Specter and again it is a 
privilege to be here to provide testimony, and I'm very 
grateful for the opportunity.
    Senator Specter. You didn't have to put in your curriculum 
vitae that you were from Australia, we could have told that 
right away.
    Dr. Pestell. Being Australian all the way through, is that 
okay?
    Senator Specter. Yep.
    Dr. Pestell. If I may, I thought I'd start with a couple of 
personal comments and then read----
    Senator Specter. Pull the microphone a little closer. Those 
television cameras will reach a great many more people then the 
number who are present in the audience.
    Dr. Pestell. Is that louder now? Okay. If I may, I'd like 
to start with a couple of personal comments and then read part 
of my testimony, and then summarize a couple of thoughts of 
action steps moving forward.
    Senator Specter. All of the written statements will be made 
a part of the permanent record.
    Dr. Pestell. In brief, I came to the country almost 20 
years ago because I thought this was the place where many 
different types of cancer would be cured.
    I absolutely believe that cancer is understandable, it's 
treatable and it's beatable. I believe that the combination of 
the process of funding this type of destination will inevitably 
lead to a continuing number of cancers that are cured and that 
will happen in this country. Again, I believe it's very much a 
part of a team effort that will make that possible. I'll read 
part of my testimony now, if I may, in the response to the 
concern that innovative ideas and projects were said to often 
struggle to secure the necessary financial backing to proceed, 
which was the key questions raised by the editorial. I do 
believe it warrants further analysis.
    I'm a long-term cancer researcher and the current director 
of the Kimmel Cancer Center at Thomas Jefferson University, and 
I suggest an alternative view and suggest an approach to 
examining further these conclusions using more quantitative 
metrics.
    I think extraordinary progress has been made in the 
understanding and treatment of many different types of cancers 
and through NCI-supported research tremendous progress has been 
made.
    I think highlights include the revolution in thinking based 
on the discovery of oncogenes, the use of molecular genetics to 
determine therapy and disease outcome, and that has certainly 
improved the quality of care for our patients.
    NCI-supported research has lead to a continuing revolution 
in the way that cancer, its diagnosis and its treatment are 
approached. I think of considerable importance is that NCI has 
supported a very cost-effective biomedical research 
infrastructure, which are these NCI-designated cancer centers, 
because the fundamental discoveries that are required to cure 
the various diseases that are cancer requires sustain, support 
and in a constant environment.
    The Kimmel Cancer Center was established in 1991 as an NCI-
designated cancer center and it conducts basic clinical 
research and has an education mission.
    There has been a substantial rise in the number of 
scientific publications that have occurred in the last 3 or 4 
years, since I have had the privilege of taking over the cancer 
center, and I wanted to give a couple of examples of major 
discoveries that have been supported by NIH, and that have, 
importantly, impacted the quality of care and cure of several 
diseases.
    Recent fundamental discoveries of transformation content 
include the discovery that colon cancer is maintained by a 
paracrine mechanism involving a secreted factor. This really 
changes the way of thinking about colon cancer.
    Both of my parents died of colon cancer and we have been 
very focused and interested in changing the paradigm of how we 
treat these diseases, which affect so many individuals.
    If we think differently about the way that cancers are 
caused and these secreted factors and we can develop antibodies 
to those secreted factors, we can intervene in a very real way.
    The second discovery, which has taken place at the Kimmel 
Cancer Center, is the discovery of a ``commandeering tumor 
suppressor model.'' This changes, completely, the paradigm of 
thinking. Its research has been supported by the NIH and it 
changes the paradigm from the idea that tumor suppressor's work 
within a cell, to the idea that tumor suppressors commandeer 
the local tissue environment and that there are many factors 
within the local area of the tumor, and these maintain and 
sustain the tumor. This change in thinking has lead to the 
development of a new treatment which involves an antibody, and 
we have shown in mice, using this new understanding that we can 
completely block breast cancer metastasis in mouse models. So, 
again, a complete paradigm shift and this research have been 
supported by NIH.
    The third paradigm shifting, NIH funded research, that I 
would like to mention today is some work done on a gene called 
Caveolin1 and this research has changed the fundamental 
thinking on breast cancer, and has led to a new classification 
or proposed new classification of this disease. Looking at the 
fibroblasts within the tumor, rather than the epithelial cell, 
this subtle but very important change, has led to a completely 
different marker for prognosis in patients who are treated with 
breast cancer.
    So, I would like to suggest a couple of practical thoughts 
moving forward, if I may. These are to enable us to determine, 
quantitatively, the outcome of some of the research. How do we 
know this research is innovative? How do we know it will 
succeed? It's obviously an important balance between these two 
questions.
    So, I think it is important for us to develop surrogate 
measures of the impact of the researcher's work. There are a 
number of surrogate measures that exist. One of them is the 
citations of an individual investigator's work over a certain 
period of time. The second is the H-index, which is predictor 
of an individual investigator's scientific impact; the number 
of times there work is quoted.
    The third is the G-index, which looks at--if you like 
stocks on the rise, the relative effectiveness of----
    Senator Specter. Dr. Pestell, about how much more time will 
you require?
    Dr. Pestell. About 35 seconds.
    Senator Specter. Okay.
    Dr. Pestell. All right.
    Another idea, of course, is to look at the number of 
publications that appear from team research in an organization.

                           PREPARED STATEMENT

    So, if I could in closing, just recommend that this is an 
opportunity to look for better surrogate measures for 
determining the innovative impact. We can subtlty turn the 
direction of the NIH criterion to include the emphasis on 
innovation.
    I know that a new scoring has been developed which 
emphasizes innovation within NIH funded Arrow One Grants. I 
think it's important for us to develop new metrics to determine 
the potential of innovative research and, finally, I think it 
is important to set aside a larger pool of funds to support, 
specifically, high-risk innovative grants, and the 
identification of that subset of new funding warrants further 
attention.
    [The statement follows:]
                 Prepared Statement of Richard Pestell
    I have been asked to respond to a recent New York Times article. 
This article highlighted that the National Cancer Institute (NCI), 
which awards billions in Federal funding for research grants, ``tends 
to choose projects that are not likely to result in groundbreaking 
discoveries related to treating and curing cancer''. Innovative ideas 
and projects were said to ``often struggle to secure the necessary 
financial backing to proceed''. The questions raised by this editorial 
warrant further analysis.
    As a long-term cancer researcher and the current Director of the 
Kimmel Cancer Center at Thomas Jefferson University, I would suggest an 
alternative view and suggest an approach to further examining these 
conclusions using more quantitative metrics. Extraordinary progress has 
been made in the understanding and treatment of cancer, through NCI-
supported research. Highlights include the revolution in thinking based 
on the discovery of oncogenes, and the use of molecular genetics to 
determine therapy and disease outcome. NCI-supported research has lead 
to a continuing revolution in the way that cancer, its diagnosis and 
its treatment are approached. Of considerable importance the NCI has 
supported a cost-effective biomedical research infrastructure required 
to conduct collaborative team-based groundbreaking discoveries, in 
particular through the support of NCI-designated Cancer Centers.
    The Kimmel Cancer Center, established in 1991, is an NCI-designated 
center conducting basic and clinical research and an education mission. 
The Kimmel Cancer Center currently has several hundred active members 
in both the clinical and basic sciences. The Cancer Center is funded by 
$19.7 million per year of NCI peer-reviewed funding and $46.8 million 
in peer-reviewed cancer funding. The NCI peer-reviewed funding has 
increased since 2005 from $11.4 million to $19.7 million and peer-
reviewed cancer funding has increased from $31.8 million to $46.8 
million. As indicated below, the research supported by this funding has 
led to a dramatic increase in the number of scientific publications per 
year by basic and clinical scientists in the Cancer Center. I will 
herein use an NCI-designated Cancer Center to illustrate their 
importance.
    The Kimmel Cancer Center has a long track record of fundamental 
transformational research discovery supported by NCI grant funding. 
These basic molecular genetic studies have been translated into 
clinical research and clinical care. These discoveries include the 
identification and characterization of the genes encoding the mismatch 
repair enzymes involved in repairing the damaged DNA which contributes 
to colon cancer onset and progression.
    Recent fundamental discoveries of transformational content include:
  --The discovery that colon cancer is maintained by a paracrine 
        mechanism via a secreted factor GCC (guanylyl cyclase c). These 
        studies provide a potential alternative model for colon cancer 
        treatment--envisaging the disease as a disease of hormonal 
        imbalance. These studies are paradigm shifting as they provide 
        a secreted factor as a tractable target for intervention.
  --The discovery of the ``commandeering tumor suppressor model''. In 
        this model one gene commands the local tissue microenvironment, 
        and very importantly cancer stem cells, to affect the different 
        cell types that conspire in the progression of cancer. The 
        first evidence was the discovery that a cell fate determination 
        factor, Dachshund, blocks breast cancer metastasis in vivo and 
        the identification of the mechanism promoting metastasis via a 
        secreted factor. Further, these studies demonstrated antibodies 
        to this secreted factor abrogated the breast cancer metastasis 
        to the lungs in animals. The demonstration of a similar 
        situation in humans could lead to treatments to limit the 
        spread of breast cancer cells in patients and thereby reduce 
        the lethality of breast cancer.
  --Very recent studies by the Kimmel Cancer Center have shown that 
        breast cancer disease outcome is predicted by levels of a 
        specific protein called Caveolin1 in the breast fibroblasts. 
        These discoveries have lead to a new prognostic indicator for 
        therapeutic response and provide a fundamental new mechanism by 
        which breast cancer onset and progression occurs. Further, 
        these studies provide the basis for a proposed new 
        classification of breast cancer. It is anticipated that these 
        discoveries will have a major impact in increasing the targeted 
        efficacy of breast cancer treatment in the coming years, 
        focusing particular treatment regimes to those who would be 
        responsive and sparing others from difficult treatment to which 
        they would not respond.
    The key questions raised by the New York Times article are whether 
the established NCI/NIH funding mechanisms limit the funding of truly 
transformative research and how can we determine the relative 
effectiveness and impact or medical research conducted by NCI-funded 
investigators? Several surrogate measures are currently used at this 
Cancer Center to determine the impact of an investigator's research on 
the biomedical community:
  --The number of citations for the individual investigators work.
  --The H-index which is based on the set of the scientist's most cited 
        papers and the number of citations they have received in other 
        people's publications. A value of 45 or higher is frequently 
        associated with membership in the highly prestigious and 
        selective United States National Academy of Sciences; and a 
        value of 18 is frequently associated with promotion to a full 
        professorship.
  --The third index, the G-index, is used for quantifying scientific 
        productivity of physicists and scientists based on publication 
        record. It is often difficult to predict the impact or 
        transformational nature of specific research. However, we 
        believe these surrogate measures represent useful quantitative 
        aspects. For example, approximately 15 percent of the Kimmel 
        Cancer Center members, supported by our major National Cancer 
        Institute funding mechanism have an H-index of over 30, and 
        approximately 10 percent have an H-index over 45. Such data 
        strongly indicate that the NCI support for research by our 
        Cancer Center members translates into research of high impact 
        on the biomedical community.
  --Another reflection of the significant activity of the researchers 
        in the Kimmel Cancer Center is the number of publications by 
        Cancer Center members in scientific journals, and the increase 
        in publications per year by clinical and basic scientists in 
        the Cancer Center. For example, over the past 3 years, the 
        number of publications per year by Cancer Center members in 
        scientific journals has increased by more than 40 percent, 
        reaching a level of almost 400 publications per year in the 
        past year.
  --An additional important surrogate measure of the effectiveness of 
        NCI in supporting translational and transformational research 
        include patents submitted and/or issued and what companies 
        developed from those new scientific discoveries, in other words 
        how do laboratory discoveries get translated into the realm of 
        public availability. The Kimmel Cancer Center, has been issued 
        80 patents and has 61 patents pending.
    Several important questions remain to be formally addressed:
  --What are the superior quantitative measures of the impact of new 
        research supported by NCI? Ambitious goals of the clinical 
        translational science awards include improving the health of 
        regions and or populations. NCI-designated Cancer Centers have 
        developed metrics to improve equitable access to cancer 
        patients. Metrics related to the quality of life of patients 
        with cancer, in addition to mortality, represent important 
        priorities related to treating cancer.
  --Are there additional surrogate measures of the research vitality in 
        the United States reflected by NCI investment. One possibility 
        includes the influx of qualified researchers for positions in 
        the United States, which may reflect a perceived unique 
        opportunity to conduct high impact medical research by the 
        global academic community. A formal comparison of scientific 
        impact by NCI-funded research with other cancer funding 
        agencies may be warranted and would be required to formally 
        establish.
  --How can the current research culture promote ``groundbreaking 
        discoveries related to treating and curing cancer''. Promoting 
        transdisciplinary research (biology/nanotechnology/physics/
        material sciences/stem cells) with an RFA intention of 
        groundbreaking discoveries may be helpful. Emphasis by broad 
        think tank input on areas of research that are most likely to 
        provide groundbreaking results, such as stem cell research. 
        Emphasis within journal publications, promotion and tenure 
        committees, coupled to the surrogate measures above may enhance 
        the focus on all important transformational discoveries. 
        Collectively this report emphasizes that this is an excellent 
        time to evaluate researchers funded by NCI or other cancer 
        agencies for their impact using the currently available 
        surrogate measures.

    Senator Specter. Thank you very much Dr. Pestell.
    We now turn to Dr. Michael V. Seiden, President and CEO of 
Fox Chase Cancer Center; principal investigator of the Fox 
Chase University of Pennsylvania, NCI Grant, undergraduate 
degree at Oberlin, M.D. and Ph.D. at Washington University 
Medical School.
    Thank you for joining us Dr. Seiden and we look forward to 
your testimony.
STATEMENT OF DR. MICHAEL V. SEIDEN, PRESIDENT AND CEO, 
            FOX CHASE CANCER CENTER, PHILADELPHIA, 
            PENNSYLVANIA
    Dr. Seiden. Thank you Senator.
    The critique of federally funded cancer research in the New 
York Times recently was, in my opinion, largely on target. 
While the current review process for proposals does a good job 
of ruling out bad research, we do have difficulty identifying 
and perhaps, more importantly, funding the kind of truly 
innovative research that might lead to dramatic paradigm shifts 
and fundamentally change the management of the cancer patient 
and the cancer problem.
    Having said that, I don't want to insinuate that the 
current funding strategies don't work, they do work. We've made 
significant progress in cancer in recent years.
    Cancer statistics are improving slowly. I also applaud the 
NIH effort of introspection on its peer-review process, and I 
do believe that new changes require careful review, since they 
do offer the potential to change the way we refund research. 
However, the peer-review process, as currently structured, does 
have some important blind spots. For perfectly understandable 
reasons the process tends to support the status quo and 
encourage a systematic cautiousness that has the unintended 
consequence of discarding the highest risk, most innovative, 
and in some cases, what might ultimately prove to be the most 
promising research proposals.
    I'll suggest three specific strategies to continue to 
challenge NCI and all scientists to shift toward more 
innovative research.
    First suggestion is focused on supporting theme based as 
compared to what I might call specific aim-based science.
    At Fox Chase Cancer Center, for example, we launched an 
initiative we called the Keystone Programs of Collaborative 
Research, designed to bring the power of team-based science to 
bear on some of the most important cancer problems.
    The scientific theme for each Keystone Program was 
conceived by a self-organized group of scientists and 
clinicians, and aimed to integrate and focus their joint 
expertise on a significant cancer problem. Beginning with more 
than a dozen proposals we conducted competitive external peer 
reviews of the team, their core competencies, prior 
accomplishments and long-term goals. Importantly, the 
applications did not include any specific aims or any specific 
details about scientific approach. The Center eventually 
awarded four Keystone Programs; $5 million in support from 
philanthropy and other internal sources. I want to emphasize 
that the Keystones articulated important themes, but not 
specific aims or experiments, given the investigators dramatic 
latitude to pursue ideas they found exciting and potentially at 
high risk.
    So, on this first example, the NCI might place a much 
larger portion of its budget into funding high-quality, multi-
functional teams that have a theme. I would encourage these 
applications to be designed in a way that emphasize specific 
gains and scientific approaches. The support should be 
structured with maximal flexibility so the teams could go where 
the science leads them.
    The funding period for these grants might be as long as 7 
to 10 years to give the scientist time to explore high-risk 
avenues of investigation without the pressure to switch focus 
or tactics to ensure incremental advances to prove to the NCI 
that they were being productive and hence, deserve refunding.
    Midterm reviews could be considered, but the metric for 
success should be evidence of creativity, not evidence of 
productivity. The initial peer review and the midterm review 
would clearly require a major shift from the current review 
process that typically looks for the number of publications and 
follow on grants, instead of really big discoveries. Indeed, 
the current grant process often rewards the proof of something 
you've already suspected or had already partially proven.
    A second strategy to boost creative science would be to 
invest in grant programs that relied less on preliminary 
findings in the review process, but instead focused on big, new 
ideas.
    A third strategy might be to build review teams that would 
not be--consciously not be laden with content experts, because 
these individuals, almost by definition, are the same people 
who have defined the current field and hence, might be least 
likely to embrace applications that espouse whole new paradigms 
or theories around an area of science.
    Importantly, I do not mean to suggest that we discard our 
current grant programs and that they are proven to produce real 
results. However, we should build new granting mechanisms that 
strongly encourage higher-risk science.

                           PREPARED STATEMENT

    In closing, it is likely apparent, but nevertheless should 
be emphasized, that building new programs will threaten the 
solvency of the existing programs, unless there is ongoing 
increases in the NCI budget.
    The cancer community greatly appreciates your efforts, 
Senator, in building a stronger NCI and wishes you continued 
success in expanding funds to this important institution.
    Thank you for your time.
    [The statement follows:]
                Prepared Statement of Michael V. Seiden
    I want to begin by thanking you for the opportunity you've given 
this group today to share its thoughts about how we can make cancer 
research smarter and more productive in countering this terrible 
disease. The city of Philadelphia was, in many ways, the birthplace of 
American medicine more than two centuries ago, and the caliber of the 
stellar institutions represented by the leaders present here today 
suggests that this great city will also help define the future of 
medicine--particularly cancer medicine.
    The critique of federally funded cancer research in The New York 
Times recently was largely on target. While the current review process 
for proposals does a good job of ruling out bad research, we do have 
difficulty identifying and funding the kind of truly innovative 
research that might fundamentally change our view on the cancer 
problem.
    Having said that, we should stop short of a flat statement that 
current funding strategies don't work--they do work. Significant 
progress has been made against cancer in recent years. More people are 
surviving longer than ever before, and the number of new drugs on the 
market and in clinical testing--many in entirely new categories of 
action--is climbing every year. And like our peers at other research 
organizations, including those represented here today, Fox Chase 
scientists have been generally well funded to pursue vital 
investigations that are making a difference against cancer.
    The peer-review process as currently structured does have important 
blind spots, however. For some perfectly understandable reasons, the 
process tends to support the status quo and encourage a systemic 
cautiousness that has the untended consequence of discarding some of 
the most promising research proposals being offered up by some of our 
most creative scientists.
    So the question before us today is this: What can be done to change 
this unfortunate reality? What can be done to intelligently identify 
and support potentially game-changing new ideas in the fight against 
cancer?
    One thing we might do is look to the National Cancer Institute 
(NCI) cancer centers to see what local solutions some of them have come 
up with to spur and develop the most innovative ideas from their own 
research faculties. Might some of these offer models for change at the 
Federal level?
    At Fox Chase Cancer Center, for example, we last year launched an 
initiative we call the Keystone Programs for Collaborative Research, 
designed to bring the power of team-based science to bear on some of 
the most important cancer problems today. The scientific theme for each 
Keystone program was conceived by a self-organized group of scientists, 
clinicians, and other research professionals at Fox Chase seeking to 
integrate and focus their joint expertise on a significant cancer 
question identified by the group. There are currently five of these 
research programs at Fox Chase. Beginning with more than a dozen 
proposals, we conducted a competitive external peer-review, eventually 
awarding each Keystone program at least $5 million in support from 
philanthropy and other internal sources over 5 years. These efforts 
articulated themes but not specific aims or experiments that would be 
conducted by the group. Early indicators suggest that these programs 
are bringing people together in entirely new collaborative combinations 
that are bridging disciplines and silos across Fox Chase and 
encouraging a new level of creativity among our already terrific 
scientists.
    So one solution to the problem at hand might be for the NCI to 
place a much larger portion of its budget into funding high-quality, 
multi-functional teams that have a theme but not necessarily specific 
aims. This support should be structured with maximum flexibility so 
that the teams could go where the science leads them. The funding 
period for these grants should be long--7 to 10 years--to give the 
scientist time to explore high-risk avenues of investigation without 
the pressure to switch focus to making more sure incremental advances 
to prove to the NCI that they are being productive and hence deserving 
of refunding. Mid-term reviews should be considered, but the metric for 
success should be evidence of creativity not evidence of productivity. 
This would clearly be a major shift in the review process, which 
typically looks for the number of publications and follow-on grants 
instead of really big discoveries. Indeed, the current grant process 
often rewards the proof of something one already suspected or had 
already partially proven prior to submitting the grant. Ideally, these 
teams should be required to include junior faculty, who will also 
receive sustained funding.
    In parallel with the availability of this new funding, the research 
universities would need to enter into a more robust dialogue about 
rewarding biomedical scientists for this kind of team play as opposed 
to encouraging primarily the pursuit of individual grants.
    Another move the NCI could make to boost the most creative science 
would be to invest in grant programs that eliminated the use of 
preliminary findings in the review process, substituting instead an 
assessment of prior accomplishments by the investigator. Currently, 
even for grants where preliminary data is called optional, there is a 
bias to fund those grants with the largest amount of this not-so-
optional preliminary data.
    Another strategy that would help identify the most innovative 
cancer research for funding would be to build multi-disciplinary and 
perhaps multi-agency review teams. These review teams would consciously 
not be laden with content experts, because these individuals, almost by 
definition, are the same people who have defined the current field and 
hence might be least likely to see whole new paradigms.
    These are only a few of the approaches that might be taken at the 
Federal level to do a better job of identifying and supporting truly 
groundbreaking research into cancer. And we must act. The need, as 
everyone in this room understands, is compelling. The NCI cancer 
centers were not designed to be grant-getting machines. They were 
created as a way to focus our energies and talents as a nation on 
eliminating cancer for our patients. If we can refocus the research 
process to adopt some of the ideas put forth here today, I know we can 
do even more to find needed answers for the patients we serve every 
day.
    Thank you very much for your kind attention.

    Senator Specter. Thank you very much Dr. Seiden.
    We will now turn to Dr. Craig Thompson, director of the 
University of Pennsylvania, Abramson Cancer Center, which is a 
NCI-designated cancer center. Dr. Thompson is a Dartmouth grad 
and has a medical degree from the University of Pennsylvania.
    Before your clock starts to run, Dr. Thompson, how does 
somebody get a Chair name for him while he's still on the 
faculty, like Dr. Glick has?
    Dr. Thompson. It's possible only when one has an 
inspirational leader such as Dr. Glick, who you mentioned 
earlier, Senator. We were able to create a Chair in his name 
because of the dramatic benefit he has provided to the patients 
here in the Delaware Valley in cancer, and as a result, Dr. 
Glick has gone back, as you said, to patient care, and I have 
taken over his duties in administration with the support of his 
Chair.
    Senator Specter. Is it common to have a Chair named during 
a person's lifetime----
    Dr. Thompson. It is----
    Senator Specter [continuing]. And still well practice?
    Dr. Thompson [continuing]. Possible, but extraordinarily 
rare.
    Senator Specter. So how do your feet feel in those big 
shoes?
    Dr. Thompson. They're very big shoes and I'm still trying 
to fit them, sir.
    Senator Specter. All right, on to the subject matter.
STATEMENT OF DR. CRAIG B. THOMPSON, M.D., DIRECTOR, 
            ABRAMSON CANCER CENTER, UNIVERSITY OF 
            PENNSYLVANIA, PHILADELPHIA, PENNSYLVANIA
    Dr. Thompson. Well, I'm pleased to comment on the recent 
concerns about the progress in cancer research and treatments. 
I think it's important for us to remember what really has been 
accomplished in the last two decades.
    Over this decade cancer death rates have declined 
progressively for both men and women. Since 1990, the death 
rate from cancer has declined 10 percent in women and 19 
percent in men. That's a dramatic improvement over what had 
occurred previously.
    The doubling of the NIH budget from 1998 to 2004 brought 
forward a Bolis of new approaches for the treatment of cancer. 
These will provide benefits to cancer patients for the next 
several decades.
    Over the last 5 years, however, support for innovative 
research has declined in cancer as the national priorities in 
other areas have arisen. Funding has actually declined 12 
percent in terms of cancer research support. This has raised 
concerns by the community that innovative new ideas are not 
being funded. Only 1 in 10 new applications to the NIH are 
funded and research has increasingly shifted; as research into 
cancer is a complex disease, requires additional expertise to 
team-based science.
    The NIH is responding in the way that Dr. Tabak addressed 
to try and stimulate in this new era of team-based science, new 
innovative approaches and award new types of grants. But, in 
addition, this is a national effort.
    What you see here before you are the directors of the 
cancer centers that are supported in part by the National 
Institutes of Health, here in the Philadelphia area. All of us 
have responded to this challenge in our own ways to help 
support and maintain innovative research.
    The comprehensive cancer centers, like the Abramson Cancer 
Center receive funds from the NIH and other sources that we 
pull together to support pilot grants for new, young 
investigators, and developmental grants for senior 
investigators who have new ideas.
    Team-based science awards that come out of the NIH have, as 
a component, the training of our youngest and brightest new 
scientists as part of that team.
    I just want to provide two examples of what's happened at 
the Abramson Cancer Center recently.
    As part of our core grant support from the National 
Institutes of Health, we receive funding for developmental 
projects and we awarded one to a young cancer researcher who 
came up with the innovative, but unproven idea that one of the 
complications of aggressive treatment for cancer; such as, you 
yourself experience Senator Specter, is that it causes a risk 
of instability to the patients DNA or chromosomes. We know 
because of the National Genome Sequencing efforts, that these 
instabilities arise as a complication of cancer therapy, and 
she realized that the use of drugs that have been developed for 
the treatment of HIV might actually benefit cancer patients by 
preventing those instabilities of the chromosomes as cancer 
patients are treated; therefore, decreasing the rate of cancer 
in secondary cases of patients that have been treated with 
cancer. She was able to receive developmental funds directly 
from the Abramson Cancer Center to support that idea, obtain 
preliminary evidence to support that idea in animals, and now 
for the first time is a fully funded researcher from the 
National Institutes of Health funded with that opportunity.
    In one of our innovative program project grants, team-based 
science, lead by Celeste Simon, a senior, female investigator, 
she was able to fund a young junior investigator to use a new 
approach to cancer treatment using anti-malarial drugs. Drugs 
that were first developed to prevent malaria in patients that 
visit areas where malaria is endemic for the treatment of 
metastasis in cancer and prevent the most dreaded complications 
of cancer; metastasis, that young investigator, after 4 years 
of funding within the program project, now has received his own 
funding from the National Institutes of Health.
    So, what we are doing in the Nation's effort is to spur 
that innovation locally, so that it can receive recognition as 
more proof of principle is obtained for those researchers.

                           PREPARED STATEMENT

    Finally, I think though, we are all here today because 
there is no doubt that only 1 in 10 grants being funded means 
that there are new ideas that are not being supported; the 
excitement of the air, our stimulus funds and what they provide 
in terms of opportunities to fund new, innovative approaches in 
research and development in cancer care that will hopefully 
reverse this trend.
    It is no doubt that these funds will stir new scientific 
discovery and innovation. Just look at the number of grants 
that have been recognized as having been submitted in response 
to the stimulus packages. But what is needed is additional 
long-term support for cancer research of this complex disease, 
if America is to continue to lead the world's war on cancer as 
it has for the last three decades.
    Thank you Senator.
    [The statement follows:]
                Prepared Statement of Craig B. Thompson
    Good morning Senator Specter and thank you for inviting me to 
present testimony today. I am the Director of the Abramson Cancer 
Center, the Associate Vice President for Cancer Services at the 
University of Pennsylvania Health System, and the John H. Glick 
Professor of Medicine and Cancer Biology at the University of 
Pennsylvania School of Medicine here in Philadelphia. I have been an 
(National Institutes of Health) NIH-funded investigator for more than 
20 years and before that served as a medical officer in the U.S. Navy 
for 8 years. My current research focuses on studying how alterations in 
the control of cell metabolism contributes to cancer cell development 
and survival. Previously, my research has contributed to the 
development of new treatments for autoimmune diseases and leukemia.
    At Penn Medicine we are dedicated to our joint missions of medical 
education, biomedical research and excellence in patient care. Each 
year we teach over 700 students, train 1,300 residents and provide care 
associated with 80,000 inpatient stays and over 1.4 million outpatient 
visits. In 2008, we received over $390 million in funding from the NIH 
for discoveries to improve human health. Of this total, investigators 
in our National Cancer Institute (NCI) designated Comprehensive Cancer 
Center received more than $140 million in NIH funding. NIH grant 
support received by Penn Medicine has enabled innovative, cutting edge, 
and potentially revolutionary research into cancer and related 
diseases. This observation applies to bench research as well as more 
mature research involving patients. Consequently, I like others was 
puzzled by a recent New York Times article suggesting that the NIH 
funds only projects that are based on conservative science and are 
``unlikely to take significant steps towards curing cancer or other 
diseases''.
    For example, at the Abramson Family Cancer Research Institute, the 
NIH has provided funding for research into developing techniques to 
genetically modify immune cells so they selectively attack the 
patient's ovarian cancer, an exciting, but unproven technique to 
improve immunotherapy.
    In addition, investigators from the Abramson Cancer Center received 
grants to determine if the genes a patient inherits predispose him or 
her to neuroblastoma or testicular cancer, cancers that 
disproportionately affect children and young adults. These studies have 
led to dramatic breakthroughs in our understanding of the causes of 
such tumors, and challenging the dogma that these diseases result from 
mutations that arise during development.
    Penn Medicine researchers recently received funding for team 
science approaches to: (1) Develop new imaging modalities to improve 
cancer diagnosis using techniques that have not previously been used in 
medicine, and (2) study whether metabolic alterations exhibited by 
cancer cells can be exploited therapeutically. These areas of 
investigation were previously believed to be impossible to exploit by 
the cancer community.
    Finally, the NIH has continued to fund our brightest and most 
innovative junior scientists. One junior investigator received funding 
last year to develop an entirely new approach to cancer treatment 
through inhibiting a process known as autophagy, which is largely 
unexplored in cancer biology. Another junior investigator received 
funding to explore the use of anti-HIV drugs as cancer therapies.
    We, like all institutions engaged in biomedical research, have been 
greatly concerned that NIH funding has remained flat in recent years. 
From fiscal year 2003 through fiscal year 2008, we estimate that the 
purchasing power of the funds allocated to NIH actually decreased by 
12.3 percent. Consequently, we would agree that potentially worthwhile 
avenues of investigation may not have received adequate funding due to 
financial constraints. Still, the projects described above were funded 
by the NIH. Although some may view these projects as ``risky'', such 
studies have the potential to revolutionize cancer care. The strongest 
of such applications and those most likely to be translated into direct 
patient benefit have continued to be funded, and we heartily welcome 
the additional research support made available through the $10 billion 
awarded NIH through the American Recovery and Reinvestment Act.
    In closing I want to be clear that, while we support Ms. Kolata and 
the New York Times' goal of ensuring funding for research is granted to 
projects that show the most potential to produce results that further 
the goal of curing cancer, I dispute the allegations that the NIH and 
NCI have failed in this task. These agencies are continuously exploring 
the funding of new research ideas that have the potential to be 
paradigm-shifting and thus have high potential for leading to 
fundamental improvements in cancer prevention, diagnosis, and 
treatment. I again thank Senator Specter and the rest of the 
subcommittee for having me here today, and for their attention to this 
important matter.
    Thank you.

    Senator Specter. Thank you very much, Dr. Thompson.
    Our next witness is Dr. Eileen Jaffe, Professor and Senior 
Member at Fox Chase Cancer Center, where her research is in the 
field of enzymology, undergrad degree from State University of 
New York and a Ph.D. in biochemistry from the University of 
Pennsylvania.
    Thank you for joining us this morning, Dr. Jaffe, and we 
look forward to your testimony.
STATEMENT OF DR. EILEEN K. JAFFE, ADJUNCT PROFESSOR, 
            UNIVERSITY OF PENNSYLVANIA, FOX CHASE 
            CANCER CENTER, PHILADELPHIA, PENNSYLVANIA
    Dr. Jaffe. Thank you, Senator Specter,, for the opportunity 
to speak to you today and particularly for your concern about 
how we might spur scientific research.
    The peer-review process that's used by the NIH struggles to 
support innovative research. This problem is inherent to peer 
review and it's not specific to the cancer problem, and I've 
been a researcher, for more than 25 years, at the Fox Chase 
Cancer Center since 1991.
    I've served on multiple peer-review panels including study 
sections of the NIH. I have submitted proposals for review and 
I have been funded continuously by the NIH since the early 
1980's.
    So, from my perspective, peer review works. It works to 
identify the best and strongest science within the current 
paradigms.
    However, as Gina Kolata's article pointed out, peer review 
fails to support the sort of innovation that will move science 
forward rapidly. Instead peer review supports safe, incremental 
advances. This is primarily a result of human nature. It's 
exacerbated by the current level of funding. While the pool of 
money available to research grants is much larger than it was a 
few decades ago, the pool of applicants is also considerably 
larger.
    The intense competition that results from this makes 
reviewers very cautious in their selection and, as a result, 
there is an inherent bias against bolder, challenging ideas. 
The problem is rooted in human nature. True innovation is seen 
as different, and the human response to different is suspicion. 
This is often interpreted with responses like, I don't like 
this. There must be something wrong with this. I must find 
fault with this. Right now, the review process is such that two 
reviewers are asked to write a detailed review and often there 
is a third or fourth reviewer who gets to comment, read the 
proposal. If two of the assigned reviewers rate a proposal as 
outstanding, which is the highest score that you can get, but a 
third senses that human discomfort that comes from being 
presented with something different, that's enough to dismiss 
the proposal.
    Allow me to use my own research as an example.
    About 6 years ago, we discovered that proteins could move 
in a way that hadn't been previously recognized. This went 
counter to what was in the textbooks. We saw that this 
knowledge could be used for antibiotic development and could be 
applied to diseases such as cancer. In some ways, these new 
ideas could be considered ``revolutionary,'' and many grant 
reviewers appreciated this extraordinary potential, but for 
others, the newness of the ideas was uncomfortable and they 
found a variety of faults.
    Of course, at first, I too was insistent upon verification 
of our unexpected discovery, but further testing proved our 
conclusions.
    Now, with the last one, we started to present our work at 
conferences; people would come up to me and say, but proteins 
don't do that.
    I made several different grant applications, and I use as 
an example, the most recent NIH application concerning 
antibiotic development. In this case, we had substantial 
preliminary data and the application was rated as outstanding 
in all categories by two reviewers. However, the third met the 
proposal with skepticism. So, despite the two outstanding 
marks, the grant proposal was placed well outside the funding 
range. This is an example of a split score.
    The split-score phenomenon has been a common theme for all 
of the proposals that I have submitted related to the 
application of this discovery to drug development. I suggest 
that this split score might be used to identify grant 
applications that might deserve a second look. The discrepancy 
in scores, particularly if the negative score reflects a level 
of disbelief, may be an indication that something truly 
innovative is in the works.
    We, as a society, can ill-afford to let these opportunities 
pass and a second look at these grants might be warranted.
    I propose that an independent peer-review process could be 
put in place to further evaluate split scores; particularly, 
where the primary and secondary reviewers both score the grant 
as outstanding. Of course, this independent review should be 
appropriately rigorous. But these reviewers, perhaps as part of 
what's called a special emphasis panel, would be directed to 
re-evaluate selected split scores. They would be what you might 
consider emotionally mature. They would be empowered to 
actively seek out the bold, the beautiful, potentially 
frightening and truly transformative ideas that might 
accelerate scientific progress.
    The NIH does have policies in place for supporting 
innovative research. The problem is not with NIH policy; 
rather, it is in peer review.
    For truly innovative research where there is this potential 
discomfort or fear factor and where only one reviewer needs to 
experience an emotional response to the unfamiliar, the peer-
review system fails.

                           PREPARED STATEMENT

    In summary, because scientists, like all human beings, tend 
to choose the familiar as prudent, new ideas are not being 
funded. Support for innovative new ideas is essential for 
scientists to make the kinds of leaps that we could be making 
and that our patients need and deserve.
    Whether it's through the mechanism that I've proposed today 
or through a combination of tactics, this need should be 
addressed. Of course, increased funding will help ease the 
problem, but increased funding without a change in the process 
may simply fuel biomedical growth, rather than biomedical 
innovation.
    Again, I thank you for your commitment to the NIH and for 
the opportunity to speak with you today.
    [The statement follows:]
                 Prepared Statement of Eileen K. Jaffe
    Thank you for the opportunity to speak to you today and for your 
concern with how research is funded, and how we might speed scientific 
progress by funding innovative research. Today, I am sure you will hear 
from my assembled colleagues a few ideas on how to spur innovation, and 
I intend to offer one as well that could easily be integrated into the 
existing system.
    I have been a researcher in cancer and basic science for more than 
25 years. I have served on peer-review panels and study sections for 
the National Institutes of Health (NIH) and I have submitted proposals 
for review and have been funded.
    From my perspective, peer review is probably the best approach to 
selecting solid scientific ideas for support. Peer review is also 
probably the best approach to weeding out the truly silly applications, 
or those without scientific foundation.
    In other words, the system works. In fact, the ability of our 
Government to fund scientific research, particularly through the NIH, 
is the envy of the world.
    The science of cancer medicine is just one example. While we still 
have some way to go in the field, more people are living longer with 
cancer, more people are surviving cancer and more treatment options are 
becoming available.
    However, as Gina Kolata pointed out in her June 28 New York Times 
article, there is one critical flaw. The system does not encourage the 
sort of innovation that moves science forward rapidly and, instead, 
encourages slow, incremental advances.
    This is a result of both human nature and the current level of 
funding. While the pool of money available for research grants may be 
larger than it was a few decades ago, the pool of eligible applicants 
is also much larger. Currently, only about 10 percent of grant 
applications succeed, which makes the reviewers responsible for 
reviewing grants very, very cautious in their selection. As a result, 
there is an inherent bias against bold or challenging ideas.
    The problem is rooted in human nature. True innovation is seen as 
different, and the human response to ``different'' is generally a 
feeling of discomfort, often interpreted as ``I don't like this'' or 
``something is wrong with this.''
    Right now, the review process is such that two peer reviewers are 
asked to write a detailed review of a proposal, one as lead and one as 
secondary. Often, there is a third, and sometimes a fourth reviewer who 
is assigned as a ``reader.'' This person usually writes a very brief 
statement. If two of the assigned reviewers rate a proposal as 
``outstanding,'' but a third senses that human discomfort that comes 
from being presented with something different, that is enough to 
dismiss the proposal.
    Allow me to use my own research as an example.
    About 6 years ago we discovered that proteins could move in a way 
that was not previously realized. We saw that this knowledge could be 
applied to antibiotic development and to other diseases such as cancer. 
In some ways these new ideas could be considered ``revolutionary'', and 
many grant reviewers appreciated this extraordinary potential. But, for 
others, the newness of the ideas was uncomfortable and they found a 
variety of faults:

    ``. . . it's too difficult, she must be misinterpreting her data . 
. .''
    ``. . . she hasn't proven that these drugs will actually work in 
humans . . .''

    And trust me when I tell you that at first my results surprised me 
too. However, I had the data to back up my conclusions. I also have a 
solid scientific reputation, built on a long track record of funded 
grants and quality scientific publications in top tier journals.
    I made several different grant applications. One to NIH without 
preliminary results, which addressed cancer targets, was dismissed 
without a full review. One to the National Science Foundation about 
finding drug targets, some related to cancer, received a mixed score--
ranging from outstanding, excellent, and good to just Fair. Two 
attempts at the NIH Pioneer Award program failed. However, the most 
recent NIH grant application concerning antibiotic development, for 
which we had substantial preliminary data was rated as ``outstanding'' 
by two reviewers, while the third met the proposal with skepticism.
    So, despite the two outstanding marks, this grant proposal was 
placed well outside that about 10 percent region that leads to funding.
    This ``split score,'' as it is known, should be a red flag 
signaling that the grant application may deserve a second look. The 
discrepancy in scores might be an anomaly, or it might be a good 
indication that something truly innovative is in the works. We, as a 
society, can ill-afford to let these opportunities pass.
    I propose that, in each granting agency, an independent peer review 
process ought to be put into place for these split scores, however rare 
they may be, particularly where the primary and secondary reviewers 
both score the grant as outstanding. Of course, this independent review 
system should be conducted with all the due skepticism and intellectual 
rigor that forms the basis of scientific thinking. However, they should 
also be empowered to judge scientific merits based on the reputation of 
researchers and the quality of their work. In fact, this independent 
peer-review board ought to actively seek out the bold, beautiful, truly 
transformative ideas that might accelerate scientific progress. It 
ought to identify chances worth taking.
    I also want to point out that this discussion is pertinent to all 
scientific research and not just cancer. The public generally does not 
understand that supporting basic science can lead to important 
therapies for a myriad of diseases, including cancer. Basic science 
deserves as much attention and support as cancer research. In NIH, 
basic science is supported by many of the individual Institutes, but 
most often by NIGMS.
    Fox Chase's history bears this out. In 1927, Dr. Stanley Reimann 
led with the novel belief that the key to understanding cancer lay in 
the study of normal cell growth and not only in the studies of tumor 
tissues.
    In the mid-1960s, Baruch Blumberg came to Fox Chase to continue 
work he began at NIH in understanding genetic variations among 
different populations. It was, by his own admission, a fishing 
expedition: basic science with no particular goal in mind. Yet, through 
a combination of keen insight, chance and technical prowess, Blumberg 
and his team discovered Hepatitis B, and were instrumental in creating 
a vaccine for the disease, which is often linked to the formation of 
liver cancer. Millions of people have received this vaccine, preventing 
an untold number of deaths from liver cancer. For this work, he was 
awarded the Nobel Prize in 1976.
    Then, in the late 1970s, researcher Irwin Rose along with Avram 
Hershko and Aaron Ciechanover discovered the process of how proteins 
are broken down and recycled within cells. Their discoveries 
established a new paradigm in biology that formed the basis of Velcade, 
a drug approved for multiple myeloma, and they won the Nobel Prize in 
2004.
    These are just two local examples to demonstrate that innovation 
can come from smart people performing basic science, often without a 
specific clinical goal in mind. In today's climate, it is unclear that 
either Blumberg or Rose would receive funding for their work.
    In summary, the peer review process exercised by the NIH has made 
good incremental progress toward the development of therapies for 
disease treatment and prevention. But because scientists, like all 
human beings, tend to choose the familiar in their quest to be prudent, 
new approaches are not being funded as they should in order for 
scientists to make the kind of leaps that we could be making, and that 
our patients need and deserve.
    Whether it is through the mechanism I have proposed today, or 
through a combination of tactics, this need must be addressed. Of 
course, increased funding will help ease the problem. But increased 
funding, without a change in the process, may simply fuel biomedical 
growth, rather than biomedical innovation.
    Again, thank you for your commitment and for the opportunity to 
speak with you today.

    Senator Specter. Thank you very much, Dr. Jaffe.
    We now turn to Dr. Thomas Curran, Deputy Scientific 
Director of The Children's Hospital. Dr. Curran received his 
Ph.D. from the Imperial Cancer Research Fund Laboratories in 
University College in London.
    Thank you for joining us, Dr. Curran, and we look forward 
to your testimony.
STATEMENT OF DR. THOMAS CURRAN, Ph.D., DEPUTY 
            SCIENTIFIC DIRECTOR, STOKES RESEARCH 
            INSTITUTE, CHILDREN'S HOSPITAL OF 
            PHILADELPHIA, PHIALDELPHIA, PENNSYLVANIA
    Dr. Curran. Thank you very much, Senator, and I really 
appreciate this opportunity to come here and testify in front 
of you.
    Yes, I have an accent as well. Mine comes from Scotland, 
though, not Australia.
    I came to this country to pursue a career designed to come 
up with cures for cancer. It's a long-term strategy. It's a 
very hard task and the NIH made my progress possible.
    I am representing Children's Hospital of Philadelphia 
(CHOP), the Nation's leading medical research environment for 
children. We have approximately $100 million in NIH grant 
funding annually out of the total $200 million budget. We 
really want to thank you, Senator, for making our successes 
possible because your activity as an advocate, and as a leading 
light in supporting biomedical research, is what has sustained 
the current funding climate that makes our work actually 
happen.
    The best science makes the best medicine. We feel that 
science and medicine should be tightly integrated in the 
research environment.
    Winston Churchill once said that ``Democracy is the worst 
form of government, with the exception of all the other 
forms.''
    The NIH peer-review system could be described as the worst 
form of funding science except for everything else. We really 
are the envy of the world, but we can improve the system. We 
can change it and we have to, in order to stay at the very top. 
The system works best when approximately 1 in 3 grants are 
funded.
    You've heard that right now we're funding about 10 percent 
of applications. Reviewers can pretty much spot the top 10 
percent; that doesn't require any deep thought. It's the next 
level of grants that are very hard to spot. We can predict 
breakthroughs in hindsight and it's just hard to do it before 
they happen.
    I think the solution is to ensure that competitive grants 
have the opportunity to be funded at a rate of about 1 in 3 in 
the different categories that you've heard about.
    Let me give you one example.
    In 2003, I proposed a new approach for the treatment of 
children's brain tumors, of medulloblastoma;the grant was 
turned down. The reviewers thought it wouldn't work. So, I 
revised the grant. I answered the comments, came back in and 
the grant was funded. It was very successful for the next 5 
years and then I submitted a renewal recently. It was turned 
down again. I revised the grant and persistence paid off. It 
was funded. That's the way the NIH system works. You actually 
can benefit from the comments received in peer review to modify 
an application and make it even stronger.
    I'm pleased to say that that study has led to a clinical 
trial that just opened in January of this year.
    CHOP has a major focus on the childhood cancer, 
neuroblastoma, which kills 15 percent of children with cancer. 
It's a devastating disease. CHOP has invested significant 
effort in building genomic capabilities to apply the very 
latest technologies to understanding the causes and predicting 
potential treatments for neuroblastoma.
    Recently, several studies have come out from the laboratory 
of Dr. Maris, which have underscored the success of this kind 
of approach. In fact, in one case, he identified a gene 
mutation that predicted a potential therapy and that therapy 
was already in existence for treating adult disease, and so a 
clinical trial was initiated approximately 1 year after the 
initial discovery. So, these technologies can indeed accelerate 
the application of science to medicine. But, indeed, sometimes 
the ideas are risky.
    One way to leverage those resources is to utilize 
foundation support. Foundations that usually give small, 
starter grants that can allow you to test the feasibility of 
off-the-wall or innovative ideas.
    One example of this is Alex's lemonade stand. Alex Scott 
was a young neuroblastoma patient. She lived for 4 years with 
neuroblastoma; took on all sorts of different experimental 
therapies. She died at the age of 8, but she lived a very full 
life. She launched her own foundation, which has now raised $25 
million for cancer research, based on selling lemonade in 
lemonade stands. She's inspiring to all of us.

                           PREPARED STATEMENT

    The peer-review system, as I said, is the best that exists 
in the world in terms of funding science. We can modify it. The 
changes that have been suggested, which include shortening the 
application, the emphasis on ideas, the attention paid to the 
track record of investigators, can all help find tune the 
system. But the real success will come from increasing the 
amount of funds dedicated to supporting the best and the 
brightest ideas through activities like your own, in providing 
this $10 billion fund from the stimulus package.
    Thank you very much, Senator, and I encourage you to 
continue the fight.
    [The statement follows:]
                Prepared Statement of Dr. Thomas Curran
    Good morning Senator Specter. My name is Dr. Tom Curran, I am the 
Deputy Scientific Director of The Children's Hospital of Philadelphia 
(CHOP) Research Institute, the Nation's second largest recipient of 
pediatric research funding from the National Institutes of Health 
(NIH). From 1922, when our research was conducted in a single basement 
room until the present day, when we just opened the state-of-the-art 
Colket Center for Translational Research, we have grown into an world-
renowned institution conducting groundbreaking research on diabetes, 
neonatal seizures, childhood cancer, hemophilia, pediatric heart 
disease, cystic fibrosis, nutrition disorders, and numerous other 
diseases and disorders that affect children. This work is supported by 
more than $100 million in Federal grant awards out of a total annual 
budget of more than $200 million. At CHOP, we pioneer new therapies, 
integrate novel technologies, and tackle the toughest healthcare issues 
that face our patients and their families.
    We appreciate this opportunity to testify this morning because our 
success is achieved in large part with support from the NIH. You, 
Senator, have been a leading light, and a much needed, advocate for the 
NIH and this hearing provides us all with an important forum to affirm 
the pivotal role it has played in advancing the scientific discoveries 
that lead to cures.
    While work is underway to reform our Nation's healthcare delivery 
system, we must continue to make medical research a national priority. 
This will not only save money, it will also save lives. I am confident 
that with your leadership, the NIH will continue to thrive and 
contribute even more to the health and wellbeing of current and future 
generations of Americans.
    Winston Churchill once said ``Democracy is the worst form of 
government except all those other forms that have been tried''. The 
same could be said for the NIH peer-review system. It is the envy of 
the world (it even handles reviews for other countries), but of course 
it is not perfect and it can be improved.
    The system works best when approximately 1 in 3 of all applications 
are funded. Your successful efforts to add an additional $10 billion in 
funding from the American Recovery and Reinvestment Act will help 
ensure there is room for projects that have a high risk of failure or 
that seem to have flaws. However, at present, it is my understanding 
that only 1 in 10 applications are funded--and all of these are likely 
to be excellent and meritorious. Unfortunately, because it is so 
competitive, some very good projects may not be funded at the first 
attempt due to resource limitations even with this tremendous spike. 
For example, in 2003, my proposal to develop a new treatment for 
children's brain tumors, the most common solid tumors in children, was 
initially rejected because the NIH reviewers didn't think it would 
work. After addressing their concerns, I revised the application and it 
was accepted on my second attempt.
    Five years later after we demonstrated that our approach worked 
incredibly well in mice, the renewal of the grant was turned down. Once 
again persistence paid off, and a revised grant is now funded. I am 
pleased to say that this work has led to a clinical trial of a novel 
therapy for medulloblastoma that opened early this year. 
Medulloblastoma is the most common malignant primary brain tumor, 
comprising nearly 15-20 percent of newly diagnosed cases in children.
    It is important to note that sometimes ideas are so risky that it 
is best to devote modest resources to test them out until feasibility 
has been demonstrated. In this way, NIH funding synergizes with funding 
from other sources such as foundations. For example, recent work at 
CHOP identified new genes and possible treatments for neuroblastoma, 
which causes 15 percent of all childhood cancer deaths. After just 2 
years and 2 studies, we went from having little information on what 
causes neuroblastoma to now having information on why some children 
develop it and others don't. Using CHOP's highly automated gene-
analyzing technology at our Center for Applied Genomics, we were able 
to discover that variants in the gene BARD1 increase a child's 
susceptibility to a high-risk form of neuroblastoma.
    As gene studies continue to better define the genetic landscape of 
cancer, pediatric oncologists can develop more precise, targeted 
treatments to improve survival and quality of life for children with 
this complex disease. That work is being done at The Cancer Center at 
Children's Hospital, which has one of the Nation's largest research and 
clinical programs in pediatric oncology.
    The research that leads to these innovative findings was supported 
by NIH grants, but ultimately it was the result of decades of work--
some supported by CHOP and some supported by organizations such as the 
Alex's Lemonade Stand Foundation, created by young Alex Scott, a 4-
year-old neuroblastoma patient who sought to raise money to help ``her 
doctors'' find a cure for kids with cancer. She passed away at the age 
of 8, but her legacy lives on as we get closer to a cure through the 
help of thousands of lemonade stands and other fundraising events held 
across the country by children, schools, businesses, and 
organizations--having raised more than $25 million for childhood cancer 
research. Other sources have helped fund our neuroblastoma research, 
including the Evan Dunbar Foundation, the Rally Foundation, the 
Andrew's Army Foundation, the Abramson Family Cancer Research Institute 
and the Giulio D'Angio Endowed Chair. I cite this example because NIH 
funding can be leveraged by contributions from other sources to further 
accelerate important work.
    We are all good at spotting breakthroughs in retrospect; however, 
it is pretty hard to predict them before they happen. Maintaining a 
high level of multi-year funding for innovative ideas is key to the 
translation of basic science discoveries into medical advances.
    Since we do not know with certainty where the next breakthrough in 
cancer research will come from, it is important to keep an open mind 
and to make space for high-risk/high-impact studies. The recently 
adopted modifications of the NIH peer-review system are designed to do 
exactly that.
    By placing emphasis on novelty of ideas, reducing the length of 
grant applications, and by factoring in investigator's track record, I 
believe we will increase the likelihood of supporting the best 
research.
    Again, we recognize you for working tirelessly to increase the NIH 
budget so that good ideas do not languish untested. This has resulted 
in a tremendous increase in knowledge and better treatments for cancer 
patients, as evidenced in the two examples I cited. Essentially, every 
major innovation in the understanding and treatment of cancer has 
resulted directly from NIH support.
    In closing, it is my opinion that the best way to ensure the United 
States continues to lead the world in cancer research and in the 
translation of discoveries into better treatments is to continue the 
critical investments made in the NIH to ensure it can provide long-term 
continuous support for the top third of grant applications it receives.

    Senator Specter. Thank you, Dr. Curran.
    Our final witness is Dr. Russel Kaufman, President and CEO 
of the Wistar Institute, a nonprofit biomedical research center 
in Philadelphia. It is a NCI-designated cancer center.
    Dr. Kaufman received his M.D. and undergrad degrees both 
from Ohio State University.
    Thank you for being with us, Dr. Kaufman, and the floor is 
yours.
STATEMENT OF DR. RUSSEL E. KAUFMAN, PRESIDENT AND CEO, 
            THE WISTAR INSTITUTE, PHILADELPHIA, 
            PENNSYLVANIA
    Dr. Kaufman. Thank you Senator Specter and once again, like 
all of us here, we appreciate the support that you have given 
to science.
    I think that what we can provide is perspective. We can do 
that sometimes through specific examples and that's what I'm 
going to attempt to do. I'm not going to repeat what many 
people have said because I agree with most of what has been 
said here today.
    I've been taking care of cancer patients for over 30 years. 
During that time, I've seen a number of advances. Cures for 
acute leukemia, major advances in lymphoma and you raised the 
issue of Hodgkin's disease; I think it's a good example of the 
challenges that we have in cancer therapy, because for many 
years our approach to Hodgkin's disease has been based on 
giving a kind of broad-based chemotherapy that's very toxic, 
but not targeted. Advances in science have now led to a number 
of targeted therapies. But they've yet to crack the critical 
nut that affects cancer. With Hodgkin's, only in the last few 
years have we even identified what the malignant cell is in 
Hodgkin's. So, I would say that for most of my career, we 
didn't know what the malignant cell was. We couldn't even 
target that cell. We now know that we can direct therapies 
towards that cell.
    So, to further my perspective, I've served on a number of 
review panels and for the last 2 years, I chaired the counsel 
that reviews all of the peer-reviewed grants at the American 
Cancer Society. I can tell you that the scientists take peer 
review very seriously. We've got a modest honorarium for doing 
all of this and most of us participate in this process. 
However, I think it is important for everyone to realize that 
there are two levels of review; there's the primary review and 
these reviews go to a counsel, which sets the final funding. 
This is not based on--we don't call it a quality score, we call 
it a priority score. The priority integrates a lot of different 
factors in that, so innovation, creativity, impact, all of 
those and I would say that, at least, on the last 2 years that 
I have served at the ACS Counsel, we funded many highly 
innovative grants, and in my time at NIH reviewing, we also 
fund many innovative grants.
    There are some though, as Dr. Curran has said, that are 
sent back to the reviewer and said please deal with these 
issues. By persistence, many highly innovative grants can be 
funded.
    The issue you raised about the amount of money that goes 
towards that is based on the funding organization that 
determines that priority. So, as reviewers we don't.
    I feel that the review process works well in terms of 
determining the amount of money, that's an agency decision, and 
certainly not our decision.
    Now, the other important point is that highly innovative 
science can be funded by our institutions. So, at The Wistar 
Institute, we are a small place. We don't have much money, but 
we've committed about $30 million to supporting research over 
the last 7 years. Some of that is recruiting the most highly 
innovative scientists and funding their work directly.
    On the average, it takes about a million or a million-and-
a-half to fund a new investigator and the ones we recruit are 
the most highly innovative, and the most creative.
    We don't hire people who we think are going to do middle of 
the road work. So, our own institutions and funding agency's 
such as foundations can also support high-innovation, high-risk 
research.
    Now, let me talk about the research process just for a 
minute. Some of the delays are because cancer is a very complex 
disease and we don't have what the crucial nut is that we can 
crack to solve this problem. But it's our belief that we need 
persistent and adequate funding. If we don't have adequate 
funding for research, we have all kinds of problems.
    The peer-review committees will retreat to a very 
conservative position and as Dr. Curran has said, we believe 
that somewhere between 25 and 30 percent of all grants should 
be funded, and that will improve things. It will also provide 
predictability and allow scientists to sustain their programs.
    Team-based science is very important. We have to have new 
methods for how we're going to select teams and how we're going 
to support this work. So, I fully support this and at Wistar 
and that's why we're putting together teams. Many times these 
teams are across all of our institutions. So, the team members 
belong to all of our institutions. So, this creates problems.
    As you know, baseball teams, it's hard to keep a team 
together. So, these are some of the challenges that we have 
with team-based research.
    I would like to give you--if I may, have another 30 seconds 
to give you one example, though, of where we think it is 
important to fund basic research and to understand what the 
basic problem is.
    For many years, an enzyme called telomerase has been known 
to be an essential enzyme for cancer cells to divide. 
Telomerase heals the ends of chromosomes so that they don't get 
too short and the cells don't divide. We recruited a young 
scientist; Emmanuel Scordolakis, 3 years ago and he took a 
novel approach to determine the structure of telomerase, and 
also submitted a grant to NIH. Now, we funded that work because 
we believed in it. Because our scientist felt it was important. 
He has now solved the structure of telomerase and having solved 
the structure of it, we now know where the binding pocket is 
that can inhibit that enzyme. This, we think, may be a critical 
step because telomerase is essential in all cancers. It's this 
kind of work that has to be funded, which is funding basic 
research, so that we're not just doing large clinical trials 
using drugs that aren't effective.

                           PREPARED STATEMENT

    So, we believe that this is the fundamental approach. The 
peer-review process is not broken, but can be improved and NIH 
has taken those steps to do that.
    Thank you Senator.
    [The statement follows:]
              Prepared Statement of Dr. Russel E. Kaufman
    The Wistar Institute is an international leader in biomedical 
research with special expertise in cancer research and vaccine 
development. Founded in 1892 as the first independent, nonprofit, 
biomedical research institute in the country, Wistar has long held the 
Cancer Center designation from the National Cancer Institute (NCI). The 
Wistar Institute works actively to ensure that research advances move 
from the laboratory to the clinic as quickly as possible.
    The Wistar Institute is pleased to have the opportunity to address 
the subcommittee.
    The Nation has made great progress in fighting cancer since 
President Richard M. Nixon declared a war on the disease in 1971. Due 
to advances in biomedical research, a diagnosis of cancer is no longer 
a certain death sentence. Survival rates for breast, prostate, and 
colon cancers have increased dramatically for patients whose disease is 
detected and treated early. We have cured childhood leukemia and 
testicular cancer, and we have sound strategies for preventing cervical 
cancer and melanoma. More than 40 million Americans count themselves as 
cancer survivors because of progress in cancer research.
    In recent years, however, some have argued that the pace of 
discovery has been too slow and our ability to translate new knowledge 
into effective therapies for cancer patients has been compromised in 
part by the very institution charged with managing the country's 
investment in cancer research--the NCI. Critics contend the NCI's peer 
review system is flawed, that reviewers are too conservative in their 
decision-making, choosing to fund research proposals likely to deliver 
minor advances in our understanding of the disease rather than 
innovative, out-of-the-box ideas that could yield the next major 
breakthrough or cure.
    Speaking as a cancer researcher, as chief executive officer of a 
basic biomedical research institute and director of its NCI-designated 
Cancer Center, and as one who has served on several NCI study sections 
and was recently appointed to serve on the NCI committee that reviews 
Cancer Centers, I must disagree. Overall, the NCI has stewarded Federal 
cancer research funding wisely and effectively. It has fostered broad 
involvement of the academic research community in funding decisions, 
establishing a peer-review system that is highly regarded as a model 
across the globe. By its nature, peer review ensures that individuals 
who truly understand the science select the most meritorious projects 
for funding. While many of us believe the peer review process must be 
refined as research priorities change, the fundamental tenets of this 
system remain sound.
    The nature of biomedical research has undergone a monumental shift 
over the past decade. Multi-disciplinary team science is evolving as 
the research community begins to tease apart and analyze the wealth of 
information about human biology revealed by the first complete 
sequencing of the human genome in 2003. At The Wistar Institute and 
other research institutions, scientists who specialize in diverse 
disciplines come together in collaborative teams to study human biology 
at the molecular level. The fundamental discoveries they make are the 
necessary first steps to developing better treatments and cures for 
disease.
    The nexus of this paradigm shift to team science is the NCI's 
Cancer Centers Program. Across the Nation, 63 NCI-designated Cancer 
Centers are actively engaged in transdisciplinary research to reduce 
the cancer burden. Since 1972, The Wistar Institute has maintained its 
designation as one of 7 of the 63 Cancer Centers dedicated to basic 
science. The Cancer Centers are the jewels in the NCI's crown: they 
organize the Nation's cancer-focused science into a major, 
collaborative, impactful effort. They are defined by their significant 
institutional investments in shared services and technologies, and 
their culture of collaboration--both within and among cancer centers--
whereby scientists working in teams actively pursue innovative, 
leading-edge research with the common goal of eradicating cancer. The 
Cancer Centers actually increase the return on the Nation's investment 
in cancer research by leveraging their Cancer Center Site Grants and 
other NIH funding with their own institutional funding and philanthropy 
to support research critical to advancing the field. Cancer Center 
directors also have specific developmental funds for new, highly 
innovative research areas.
    In this age of scientific revolution, our governing systems must 
evolve in stride. Recognizing that the increasing complexity and 
interdisciplinary nature of modern medical research presents new 
challenges to its peer-review system, the National Institutes of Health 
(NIH) last year undertook a thorough, formal review of its grant-making 
structure and developed a plan for making improvements. Among the key 
elements are new criteria for evaluating grant proposals which give 
weight to creativity and innovation, and allocation of more funding to 
young investigators. In addition, the plan seeks to engage the most 
broad-thinking and creative reviewers and avoid bias toward more 
conservative and proven approaches at the expense of innovation and 
originality. With these new guidelines, which are being implemented in 
the current grant review cycle, the NCI has strengthened its commitment 
to funding the best science, by the best scientists, with the least 
amount of administrative burden.
    We have achieved significant progress in cancer research, but there 
are essential facts about human biology that we must learn in order to 
be able to cure cancer. A fundamental problem remains: the prevalent 
cause of death is metastasis, the spread of cancer. Most cancers are 
highly treatable, even curable if they are caught before they spread. 
With recent advances in basic cancer research we now understand why 
cancer cells metastasize, we know the features of cells and the 
cellular environment that make them likely to spread. But we still 
don't have cures for metastatic cancer. It is critical that we continue 
to explore the basic features of cancer cells that have spread, in 
order to develop effective therapies.
    A recent discovery from a Wistar Institute lab illustrates this 
point. Last year, a young investigator determined the structure of an 
enzyme, telomerase--a discovery which is transforming the field of 
cancer research. This investigator deciphered the active region of this 
enzyme, which is essential to our growth and aging, and which plays a 
major role in the development of almost every type of cancer. 
Researchers have tried for more than a decade to find drugs to 
deactivate telomerase, but they have been hampered by a lack of 
knowledge of its structure. With this new information, we can begin to 
search for other molecules that ``fit'' the structure of telomerase and 
deactivate it, literally stopping cancer in its tracks.
    While exploration of these fundamental questions of biology might 
seem like incremental or inconsequential advances to some, they are the 
critical foundation from which we will solve the cancer problem. Under 
the stewardship of the NCI, we have seen great returns on our Nation's 
investment in the cancer research enterprise, and we are poised to 
realize the promise of discovery.
    Thank you.

    Senator Specter. Thank you Dr. Kaufman.
    I would like to ask everybody on the panel to comment about 
Dr. Klausner's statement; former Director of NCI, National 
Cancer Institute.
    He said, ``There is no conversation that I've ever had 
about the grant system that doesn't have an incredible sense of 
consensus that it is not working.''
    Would you agree or disagree with that Dr. Seiden; Dr. 
Seiden, yes, no?
    Dr. Seiden. The peer-review process is imperfect and is 
frustrating. I have to say that there has been a dialogue to 
attempt to improve it and I think that process is still under 
evolution, but it is challenging to get it right.
    Senator Specter. I take that to be a qualified yes.
    Dr. Kaufman. I disagree with his point. I think Dr. 
Klausner's a brilliant scientist, a member of the National 
Academy of Science, but hasn't really ever participated in the 
peer-review process. You know, he started his work at NIH, 
stayed there and was the Director of NCI. He's a brilliant 
scientist, but I think that the peer-review process is not 
fundamentally broken.
    I believe that all of us who participate in that, we give 
it the most honest effort possible and we believe that we are 
recommending the funding of the best research.
    Senator Specter. Well, Dr. Kaufman, would you disagree with 
Dr. Young's statement that the current system at NIH is likely 
to produce only ``incremental progress,'' and it does not 
undertake research projects, which would ``make a major 
difference in cancer prevention and treatment that are all too 
often crowded out?''
    Dr. Kaufman. Well, I believe that the current process does 
create incremental progress, but incremental progress is 
essential. But we don't know where the solution lies and so 
what groups of people are going to decide where we're going to 
take the big risks?
    Senator Specter. Well, of course, you need incremental 
progress, but do you think that a focus there crowds out a more 
transformative opportunity?
    Dr. Kaufman. Right. So the point that I made earlier was 
that we need incremental progress and we need to be stable and 
consistent, and we need to have a big enough research 
enterprise to accomplish that.
    I agree with Dr. Curran that we should be funding 25 to 30 
percent of grants that are funded, because in my perspective, 
those are the ones that are high quality. However, the funding 
agencies should set aside an adequate amount of funds to fund 
those that the review committees think really are innovative.
    I think that $35 million may not be enough money for that.
    Senator Specter. Dr. Curran, funding 1 in 3 would be ideal. 
You identified now that there is a funding in 1 in 10, what 
would it cost to fund 1 in 3?
    Dr. Curran. I can certainly provide you with those numbers 
once I calculate them. I can't give you the numbers off the top 
of my head right now.
    Senator Specter. Well, let's see. If you have 10 percent 
and----
    Dr. Curran. Right.
    Senator Specter [continuing]. You want to have 35 percent; 
that's three and one-half times $30 billion.
    Dr. Curran. Right. One other complication----
    Senator Specter. Could you do the math, Dr. Curran?
    Dr. Curran. Absolutely not.
    Senator Specter. It's more than a hundred million.
    Dr. Curran. When you change the goalpost, you also change 
the number of grants coming in. So, it's a complicated 
analysis. You can certainly say well, okay, it's just going to 
cost three times more.
    Senator Specter. Change the goalpost?
    Dr. Curran. Yes.
    Senator Specter. So if you put up more money, you get more 
applications?
    Dr. Curran. You get more applications.
    Senator Specter. So funding one 1 in 3 wouldn't be limited 
to just $100 million?
    Dr. Curran. It's a moving target and so you have to work--
--
    Senator Specter. You're moving very fast Dr. Curran.
    Dr. Curran. Very fast. You start with exactly the number 
you said.
    Senator Specter. Dr. Thompson, do you think that the 
current NIH standards are too cautious?
    Dr. Thompson. I think Tom Curran actually said it earlier. 
Tom and I talk about this a lot, since the Children's Hospital 
of Philadelphia and the Hospital of the University of 
Pennsylvania are the two entities spanned by the Abramson 
Cancer Center. We spend a lot of time talking about how you 
would improve research.
    I think the NIH system of peer review is the best in the 
world and I think that it continues to foster innovation----
    Senator Specter. The best in the world, but is it good 
enough?
    Dr. Thompson [continuing]. But I think half of that 
innovation comes from the American public itself, which is that 
if you take our best and brightest students and you put them 
into funding that exists through the channels that we've all 
discussed, they will question the discrepancies. They will come 
up with the innovative new ideas. It's that system, the 
constant challenging of new investigators brought into the 
system, against the existing principles that have given us and 
led America to be the innovation leader in research of all 
aspects, particularly in medical research over the last three 
decades.
    I think the system needs to be tweaked. We've talked about 
various ways to understand better the track record of 
individuals so that the senior scientists that can best train 
and foster people get better funding. We can talk shorter grant 
applications so more time is spent on innovative ideas, but in 
the end, the peer-review process is working and it works with 
the American young that are coming up, and with new ideas, and 
challenging existing paradigms. That's how we're going to get 
better cancer treatments and cures, Senator.
    Senator Specter. Dr. Jaffe, I'll be very specific in your 
situation. I'm going to read you part of the New York Times 
article, which praises you and points out some of the problems 
that you've had.
    It says:

    ``For 25 years, Dr. Eileen K. Jaffe received Federal grants 
to run her lab. As a senior scientist at the Fox Chase Cancer 
Center, with a long list of published papers in prestigious 
journals, she is a respected, established researcher.
    ``Then Dr. Jaffe stumbled upon results that went against 
textbook explanations, suggesting that it might be possible to 
find an entirely new class of drugs that could disable proteins 
that fuel cancer cells. Now, she wants to find chemicals that 
might be developed into such drugs.
    ``But her grant proposal was rejected out of hand by the 
Institutes of Health, not even discussed by a review panel. She 
had no preliminary data showing that the idea was likely to 
work, something reviewers always want to see, and the idea was 
just too unprecedented.
    ``Dr. Jaffe epitomizes the scientist who realizes that if 
she was single-mindedly pursuing her own unorthodox career, her 
`career may be ruined in the process,' in the words of Dr. 
Brawley of the American Cancer Society.''

    Do you think the NIH approach ought to give more latitude 
to the kind of innovative application you made?
    Dr. Jaffe. Well, we're talking about--I used as an example 
a grant that was revised, actually. It went in several times 
and the one that I talked about earlier this morning, and this 
is another application that Gina Kolata was talking about, 
which was dismissed out-of-hand for lack of preliminary data.
    These are two very different kinds of applications. To some 
extent, the work that was dismissed out-of-hand for lack of 
preliminary data, falls in that category of grants that doesn't 
require preliminary data. As opposed to the more routine RO1-
type support that I've had for the last 20, 30 years. As I 
said, the process works for funding established paradigms. The 
process fails when one sees a truly new direction that 
challenges old ideas.
    I would tell you that when we first stumbled upon our 
discovery it was disturbing. It suggested that we had to go 
back and look at the results of our laboratory for the last 25 
years, results that were published in prestigious journals, and 
potentially re-evaluate that data. Nobody wants to do that.
    Senator Specter. Thank you Dr. Jaffe.
    Dr. Pestell, let me shift gears just a little. There has 
been identified as a so-called ``Valley of Death,'' between the 
bench of the laboratory and the bedside, in terms of clinical 
application of the great research achievements of the National 
Institutes of Health scientists.
    At the suggestion of one of my former chiefs of staff, a 
young man named Craig Snyder, I've introduced legislation which 
is called, ``Cures Accelerated Network,'' which seeks to 
establish a separate but affiliated entity to NIH with 
additional funding to try and supplement clinical application.
    What do you think of that idea?
    Dr. Pestell. I think that there has never been a time in 
history where we've known so much about cancer. We have a large 
number of drugs that are available to be tested, and I think 
that streamlining that process is absolutely critical, and it's 
no doubt, the most cost-effective way of making immediate 
impact on the lives of patients with cancer.
    There is a second process, which I think, is complimentary 
to it and that's the construction of clinical translational 
sides institutes, in which the ability to increase the 
efficiency of us of clinical infrastructure that already 
exists, which can be deployed regionally will, I think, 
advantage that initiative. The time from discovery to placing 
drugs in patients is way too long. There are all sorts of 
inefficiencies which exist within the current infrastructure of 
clinical trials, deployment. We have a responsibility to ensure 
appropriate regulatory oversight, but it can be dramatically 
enhanced in the efficiency of moving these fundamental 
discoveries to the bedside.
    Senator Specter. Dr. Tabak, would you come sit next to me? 
I want to bring you back to the panel for just a minute or two.
    Dr. Seiden, in seeking to have a separate agency for cures 
acceleration to approach the ``Valley of Death,'' it's a very 
tough job to get a new entity. Did you think that there was any 
appropriate role for NIH to make grants to cover the so-called 
``Valley of Death,'' to find that the practical application to 
assist here in regulating the research achievements to the 
bedside?
    Dr. Seiden. The ``Valley of Death,'' I think is very real 
and getting wider. I think that funds particularly targeted to 
crossing ideas into the area where they can help the public are 
incredibly important.
    Whether this Agency should be part or separate from the 
NIH, I think is, at least in my mind, a little more 
complicated. One of the challenges for it to be effective it 
has to be relatively nimble and it has to figure out how to 
work with industry in a way that sometimes has been a little 
challenging for the NIH; that said, it would be important if we 
built a new government agency to do this, that it not replicate 
some of the challenges that the current Government agencies 
have with working with industry. I see that as one of the 
really big challenges.
    Senator Specter. Well, if NIH were to undertake that, the 
object is to promote health and if all of the eggs are in the 
research basket, you have the ``Valley of Death,'' and there's 
not a practical application.
    One of the factors on my mind is that NIH doesn't like to 
divert any of its funds from research and I don't blame NIH. 
NIH would like to have more money and I would like NIH to have 
more money.
    I think Dr. Curran and Dr. Kaufman are modest in just 
wanting three and one-half-times the $30 billion. I think the 
yield would be greater.
    What do you think Dr. Kaufman? Would it be realistic to ask 
NIH to do some of this work in the clinical application?
    Dr. Kaufman. Sir, I have a little bit of experience in this 
area. I'm Chair of BioAdvance, which is the Greenhouse of 
Pennsylvania, for southeastern Pennsylvania of which you're 
probably familiar with. This funds early stage biotechnology 
and there is this ``Valley of Death'' between what we do as 
academic researchers, and to get to that point, there is a 
great need for proof of concept funds.
    The SBIR process is a little bit beyond the proof of 
concept funds, so there is a gap there. But there is an 
entirely different mindset for people who fund that kind of 
research; typically, it's under economic development rather 
than NIH.
    So, in Pennsylvania, the Greenhouse, the BioAdvance, is 
under the Department of Economic Development, not under the 
Department of Health, because the ideas that need to go into 
that have to be people from the biotech industry looking back, 
and commercialization interest looking back, as much as it is 
science looking forward.
    Senator Specter. Dr. Thompson, the University of the 
Pennsylvania hospital has the benefactors of Leonard and 
Madeline Abramson, who have done so very much on supporting 
cancer research.
    Do funds from a source like that enable you to take more 
research on the innovative projects as opposed to looking to 
NIH for the peer review, which may be somewhat more 
restrictive?
    Dr. Thompson. It certainly is true that funds that have 
benefited the Abramson Cancer Center from the Abramson family 
and have allowed us to undertake innovative research that 
couldn't be funded on the scale that we do for translation. 
Because translation really requires a scale of funding that 
exceeds what we can get from standard grants as the others have 
said.
    One thing that the Abramson Institute, which is funded by 
the Abramson Family Foundation, has allowed us to do is to 
explore new ways to harness the immune system to fight cancer 
and to do real innovative clinical trials at the level of cost 
that those trials invoke, and that's been a transformative 
principle for us in the Abramson Cancer Center. So, yes, sir, 
those funds really do allow us for innovation and some way of 
receiving that kind of funds in a public-private partnership 
would greatly facilitate traversing this ``Valley of Death,'' 
as you described it.
    Senator Specter. Dr. Pestell, Jefferson has the benefactor 
of Kimmel, Sydney Kimmel, and a very generous allocation of 
personal funds.
    Does that help you more with an innovative branch, as 
opposed to being limited by what NIH will approve on grants?
    Dr. Pestell. Yes, although relatively modest by standards, 
the endowment from the gifts of Sydney Kimmel has allowed us to 
provide funds for pilot projects, which are characteristically 
out-of-the-box transformational ideas. We followed up those 
studies and many of those have led to subsequent peer-review 
funding by NIH; so, absolutely, sir.
    Senator Specter. Dr. Kaufman, you commented about $30 
million you have, is that from private funding so that you 
don't have to go through the peer-review process on that?
    Dr. Kaufman. That's right.
    Senator Specter. It's the Kaufman review process?
    Dr. Kaufman. It's the Kaufman and close associates. So, 
it's basically the program leaders within our cancer center 
that make those decisions of how we allocate those funds. But 
we can fund highly innovative research, but that money comes 
from gifts and it also comes from what we bring in from tech 
transfer, from our technology transfer; in other words, 
royalties that we get from our work. We put all of that back in 
to fund--we try to fund the most highly innovative research.
    Senator Specter. To what extent, Dr. Kaufman, do those 
royalties--how big a factor are the royalties?
    Dr. Kaufman. Well, for us they are very big. We don't have 
grateful patients, we have very ungrateful mice who don't want 
to donate anything and we don't have eventual graduates, so 
we're not a teaching institution. So, we only get our money 
from two sources. We either get it from royalties or we get it 
in discretionary dollars. We get it from royalties or we get it 
from gifts, but NIH, consistently, is the biggest source of 
funding for our research.
    Senator Specter. Dr. Seiden, how does Fox Chase do on Dr. 
Seiden: We generate a couple of million dollars a year in 
royalties, but most of our discretionary research dollars come 
from philanthropy and/or monies we make on the clinical portion 
of the business.
    Senator Specter. How about at the Hospital of the 
University of Pennsylvania, Dr. Thompson, on the royalty line?
    Dr. Thompson. I think that we, like the other institutions, 
receive royalties for a number of innovations. We receive 
royalties for the drug discovery that was described in the New 
York Times article, Herceptin, because the first antibody was 
actually made by investigators who are now on faculty at the 
University of Pennsylvania. But we also rely, equally, on 
funding from philanthropy and from grateful patients.
    Senator Specter. And Children's Hospital, Dr. Curran?
    Dr. Curran. Yes. We actually sold a royal to rights to the 
Rodatech, rotavirus vaccine for $180 million. If I may clarify 
my previous comment, I was not arguing for tripling the NIH 
budget, only the portion devoted to the competitive grant-
review process, which is a much smaller percentage than $30 
billion.
    Senator Specter. Well, Dr. Tabak, you have a fair amount of 
gris to the mill here.
    There have been some courageous statements made by a group 
of research scientists who have to come to the National 
Institutes of Health. There might be some motivation not to be 
too critical, but I think the experts here have been candid, 
somewhat critical.
    What do you have to take back to Washington on the 12 
o'clock or----
    Dr. Tabak. Thank you Senator Specter.
    First, I want to thank you for this hearing and for the 
opportunity to listen to your colleagues.
    Much of what I heard reinforces views that were expressed 
during the peer-review process, which we held regionally around 
the country and I think, in some instances, reinforces the view 
that we are on the right track on some things. But as you have 
pointed out, sir, there is more work to be done.
    I will take back the comments made by the panelists to 
discuss with my colleagues so that together, this is a 
partnership, we continue to refine things to the very best 
possible end result.
    Senator Specter. Well, thank you all.
    My own sense is having been in the field and having the 
experts from the National Institutes of Health, it is an 
enormously impressive hearing. A big U-shape 25, approximately, 
directors of the NIH come in.
    The question which I would like to pose is how long would 
it take and how much would it cost to cure Parkinson's or to 
cure juvenile diabetes? I know in asking those questions there 
is no finite answer, but when you deal with the Congress, you 
need to be if not specific, at least, speculative.
    Your judgments are very valuable. You know, obviously, a 
lot more about it then anybody else does and that's why we 
pushed to try to get answers as concrete as possible. We aren't 
really likely to fund 1 in 3 on the current standards.
    My proposal and I'm trying to get in the comprehensive 
reform, is to take the $30 billion, which we've moved only to 
slowly, it was stagnated at that point. If we add the $10 
billion more--I've talked to the chairman of the two relative 
committees, Senator Dodd on the Health Committee and Senator 
Baucus, on the Finance Committee. They have the work; it's not 
the Appropriations Committee to try to fix the new floor of NIH 
at $40 billion. You have to have realistic annual 
appropriations, but if you start from 1 in 10 at $30 billion 
and you want 35 percent, that is 3.5 of 10 percent. We're 
really not going to get there.
    So, it would be my hope, Dr. Tabak, that you would take 
back an underlying message, if not a dominant theme, that you 
need to give more attention to doctors like Dr. Jaffe, who are 
more on the transformative side, and that incremental progress 
is important. But there has to be a way to move beyond that in 
a more dramatic fashion. You take that message back and when I 
see my 99 colleagues on the Senate floor this afternoon; we're 
voting at 5:30 p.m., I'll tell them there was one unanimous 
view today, more funding.

                         CONCLUSION OF HEARING

    Thank you all very much.
    [Whereupon, at 11:30 a.m., Monday, July 6, the hearing was 
concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]

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