[Senate Hearing 107-874]
[From the U.S. Government Publishing Office]
S. Hrg. 107-874
STATUS OF THE IMPLEMENTATION OF THE FEDERAL STEM CELL RESEARCH POLICY
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HEARING
before a
SUBCOMMITTEE OF THE
COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE
ONE HUNDRED SEVENTH CONGRESS
SECOND SESSION
__________
SPECIAL HEARING
SEPTEMBER 25, 2002--WASHINGTON, DC
__________
Printed for the use of the Committee on Appropriations
Available via the World Wide Web: http://www.access.gpo.gov/congress/
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COMMITTEE ON APPROPRIATIONS
ROBERT C. BYRD, West Virginia, Chairman
DANIEL K. INOUYE, Hawaii TED STEVENS, Alaska
ERNEST F. HOLLINGS, South Carolina THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont ARLEN SPECTER, Pennsylvania
TOM HARKIN, Iowa PETE V. DOMENICI, New Mexico
BARBARA A. MIKULSKI, Maryland CHRISTOPHER S. BOND, Missouri
HARRY REID, Nevada MITCH McCONNELL, Kentucky
HERB KOHL, Wisconsin CONRAD BURNS, Montana
PATTY MURRAY, Washington RICHARD C. SHELBY, Alabama
BYRON L. DORGAN, North Dakota JUDD GREGG, New Hampshire
DIANNE FEINSTEIN, California ROBERT F. BENNETT, Utah
RICHARD J. DURBIN, Illinois BEN NIGHTHORSE CAMPBELL, Colorado
TIM JOHNSON, South Dakota LARRY CRAIG, Idaho
MARY L. LANDRIEU, Louisiana KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island MIKE DeWINE, Ohio
Terrence E. Sauvain, Staff Director
Charles Kieffer, Deputy Staff Director
Steven J. Cortese, Minority Staff Director
Lisa Sutherland, Minority Deputy Staff Director
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Subcommittee on Departments of Labor, Health and Human Services, and
Education, and Related Agencies
TOM HARKIN, Iowa, Chairman
ERNEST F. HOLLINGS, South Carolina ARLEN SPECTER, Pennsylvania
DANIEL K. INOUYE, Hawaii THAD COCHRAN, Mississippi
HARRY REID, Nevada JUDD GREGG, New Hampshire
HERB KOHL, Wisconsin LARRY CRAIG, Idaho
PATTY MURRAY, Washington KAY BAILEY HUTCHISON, Texas
MARY L. LANDRIEU, Louisiana TED STEVENS, Alaska
ROBERT C. BYRD, West Virginia MIKE DeWINE, Ohio
Professional Staff
Ellen Murray
Jim Sourwine
Mark Laisch
Adrienne Hallett
Erik Fatemi
Bettilou Taylor (Minority)
Mary Dietrich (Minority)
Sudip Shrikant Parikh (Minority)
Candice Rogers (Minority)
Administrative Support
Carole Geagley
C O N T E N T S
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Page
Opening statement of Senator Arlen Specter....................... 1
Statement of Elias Zerhouni, M.D., Director, National Institutes
of Health, Department of Health and Human Services............. 2
Prepared statement........................................... 5
Statement of Senator Deborah Ortiz, Sixth State District,
California State Senate........................................ 8
Statement of Roger Pedersen, Ph.D., department of surgery,
Cambridge University........................................... 10
Prepared statement........................................... 12
Opening statement of Senator Patty Murray........................ 13
Statement of Gerald Schatten, Ph.D., professor of cell biology,
University of Pittsburgh, director, Pittsburgh Development
Center, and deputy director, Magee-Women's Research Institute.. 14
Prepared statement........................................... 16
Statement of Curt Civin, M.D., professor of cancer research,
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins
University..................................................... 17
Prepared statement........................................... 20
Statement of George Daley, M.D., Ph.D., assistant professor of
medicine, Harvard Medical School; and fellow, Whitehead
Institute for Biomedical Research.............................. 22
Prepared statement........................................... 24
Opening statement of Senator Kay Bailey Hutchison................ 29
Prepared statement of Senator Larry Craig........................ 32
STATUS OF THE IMPLEMENTATION OF THE FEDERAL STEM CELL RESEARCH POLICY
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WEDNESDAY, SEPTEMBER 25, 2002
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, and Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 9:30 a.m., in room SD-124, Dirksen
Senate Office Building, Hon. Arlen Specter presiding.
Present: Senators Murray, Specter, and Hutchison.
opening statement of senator arlen specter
Senator Specter. Good morning, ladies and gentlemen. The
hour of 9:30 having arrived, we will proceed with the hearing
of the Appropriations Subcommittee on Labor, Health and Human
Services, and Education.
Our focus today is to examine the status and implementation
of the President's policy on stem cell research. Shortly after
stem cells came upon the scene, the subcommittee held hearings
in December of 1998, and this is our 14th hearing to follow up
on this very, very important field of medical research.
The unique opportunities for the use of stem cells have
been recognized in a wide variety of ailments. It has been a
controversial matter because the stem cells are extracted from
embryos. While there are other types of stem cells, our
hearings have disclosed that embryonic stem cells are the most
useful, and the opposition has focused on the possibility of
life being produced by the embryos. If each embryo could
produce life, that would obviously be the highest calling, but
we know that thousands are thrown away. So it is my view that
it is obviously preferable to use these embryos to save lives
as opposed to discarding them.
The President on August 9 of last year established a policy
of limiting stem cells to 63 or 67 lines, or somewhere in that
range, and a big issue arises as to whether that is adequate to
carry on the research.
During the course of the past year, we have had
considerable controversy over nuclear transplantation which
some people call therapeutic cloning, which is not cloning at
all. This is a matter which is surrounded by controversy, and I
think we have to find our way through because at least my view
from the 14 hearings we have held is that it poses an enormous
opportunity to conquer disease.
That is a relatively short opening statement to set the
parameters.
The majority leader has scheduled two votes at 10:30, which
means that the hearing will have to be adjourned for up to 30
minutes. I am going to do my best to move through the hearing
and conclude by 10:40. I will be a little late to the first
vote, but I think that is preferable than to have witnesses and
observers wait a half an hour. I know how busy the people are
who are at the hearing as witnesses and also as observers.
STATEMENT OF ELIAS ZERHOUNI, M.D., DIRECTOR, NATIONAL
INSTITUTES OF HEALTH, DEPARTMENT OF HEALTH
AND HUMAN SERVICES
Senator Specter. Our first witness is Dr. Elias Zerhouni,
Director of the National Institutes of Health. He comes to this
position with a very extraordinary record. He was executive
vice dean of Johns Hopkins University School of Medicine, Chair
of the Russell H. Morgan Department of Radiology and
Radiological Science, and Martin Donner Professor of Radiology
and Professor of Biomedical Engineering. Dr. Zerhouni received
his medical degree from the University of Algiers School of
Medicine, and he had his residency in diagnostic radiology at
Johns Hopkins. He came to this country at the age of 24 and has
had a really remarkable career.
I have already had considerable contact with Dr. Zerhouni
in his first 4 months on the job, and this is his first
appearance before the subcommittee. We welcome you here, Dr.
Zerhouni, and look forward to your testimony.
Dr. Zerhouni. Thank you, Senator Specter. I am really
pleased to be here this morning and testify about the role of
NIH in advancing the field of stem cell research. We all know
that if properly harnessed, adult and embryonic stem cells have
the potential to replace cells that are damaged or diseased to
restore vital functions of the human body.
There are ample reasons for excitement. I personally
thought this was a field that needed to grow when I was at
Johns Hopkins. There is no question that there is huge
potential and promise, and high expectations for the new
treatments that are possible with this approach are
understandable.
But we should temper these expectations by the enormous
challenges that must be addressed before the research evolves
into proven therapy. I think we are at a very early stage of
research in embryonic stem cell research and have a great deal
of basic research to conduct before we can unlock the potential
of these cells and fulfill their promise.
What I would like to do, to go over my presentation, is to
use some charts to my right to go over what the basic strategy
for research and research development will be in stem cell
research, whether adult or embryonic. We can divide that
strategy into three phases. There is the early phase called the
basic research phase, and then two follow-on phases called
preclinical and clinical phase.
The most important aspect of the basic research phase is
for us to build the scientific capability of the field by
creating career development pathways, training courses. The
most important resource for any new field is trained
investigators who are entering the field and advancing the
field. We need to establish an infrastructure with cell culture
methods, cell lines, expand the cell lines, characterize the
cell line. The puzzle has to come together then in terms of us
being able to both prove the long-term stability of these
cells. We need to characterize them fully, and we need to make
sure they are genetically stable. We need to understand the
basic reason why we are so excited about stem cells is that
they can differentiate and specialize into different cells in
the human body. We need to understand that better at the most
fundamental level, how is that done, what are the methods that
we need to develop to understand this at the gene level and the
molecular level. We need to understand how the cell cycle of
the stem cell is controlled. One of the major risks in stem
cell research is that these cells, once implanted, might revert
to their more undifferentiated state and could grow into
tumors. We need to understand that.
Last but not least, we have to have a lot of research go on
in understanding the interactions between the cell and the host
and the immunology and the transplantation biology of these
cells.
As we progress, other elements of research will have to
come into place. And this year we have had a lot of progress
made. We have shown that in fact embryonic stem cells can
differentiate into nerve tissue and insulin-producing cells.
Adult stem cells have been shown to also be able to
differentiate. And I believe that we should continue both
embryonic stem cells and adult stem cell research at the same
pace as fast as we can to go through our understanding of the
puzzle that will then lead us to the preclinical phase where we
need to have proof of concept experiments. We need to use the
technology in animal models of disease. We need to prove what
cell dosing we need to use, make sure that our understanding of
tumor formation is complete, assess whether or not the cell is
really functioning as we want to make it function, and
eventually then, once we have accumulated that body of
knowledge, go to the clinical phases of research, which are
typically divided into three phases: to test whether or not
there is any toxicity, what is the safety of these stem cells,
and what is the efficacy of these stem cells to eventually go
into therapies that will serve the public.
Now, I would like to also cover with you the work that NIH
has done over the past year in trying to advance the field.
There are two important elements that we as enhancers of the
research, as the institution at NIH that should look to
implement the research agenda--there are two resources that I
consider the most critical right now.
One is the availability of researchers. So what we have
done is try to develop training capabilities for researchers
across the Nation. We have tried to decrease the shortage of
researchers with expertise in stem cell research. We have
extended additional grants to people who have expertise in stem
cell research but not necessarily in human stem cell research.
And we will strive to make stem cell research as attractive as
possible to our most talented research scientists. So we are
soliciting grant applications and I will give you some of the
data related to that in a minute.
One of the most important stumbling blocks is to make human
stem cells more available for research. As you know, on
November 7, 2001, NIH published the registry of derived stem
cells that would be eligible for Federal funding. The registry
consists of 14 sources across the world. The cells are in
various stages of characterization and preparation for research
applications. There are many steps required to develop
embryonic stem cells from when they are first removed from an
embryo and put into culture into an established, well-
characterized embryonic stem cell line ready for distribution
to the research community.
I tried to summarize this process right here on my chart on
the left side to show you what is the exact process that we
need to go through to make cell lines widely available for
distribution. After the derivation and the placement into
culture of cells from the inner cell mass, we obtain primary
colonies, which takes 3 to 5 days, the first thing we have to
do is expand the primary colonies, then put them into
subculture wells. Now, we need to have enough expansion of
these cell lines to be able to then have enough of them to be
available for distribution. The success rate here is not very
high. Only 10 percent of these subcultures eventually go on to
establish lines that can be characterized as human embryonic
stem cell lines.
There are about 30 to 60 passages then, that have to occur
to expand the number of cells within each line. As the cells
divide, the total number of cells available to us for research
increases. But at each passage, we need to make sure that these
cells have not differentiated, and we need to have biomarkers
for that purpose. We need to have ways of making sure that
these cells still have the total potential of embryonic stem
cells. That is done 30 to 60 times, and the expansion of these
cultures is essentially the basis for the distribution that
eventually occurs. It takes about 6 to 9 months to get from
this stage to a stage where you have expanded these subcultures
successfully, you have characterized them successfully, and one
bank requires about 2 billion cells. To start to distribute
these cells to the general public, you need approximately 2
million cells per vial to do so.
So the process obviously takes a while, and NIH has been
very aggressive at, in fact, facilitating the availability of
these cell lines from the derivations that were eligible for
Federal funding. During the scaling-up process, investigators
need to repeatedly check that the cells maintain their
abilities, and once that is done, we can go forward with the
distribution.
So as a first step, Senator, toward overcoming this
challenge, NIH announced five infrastructure grant awards
totaling $4.3 million to five sources on the NIH registry,
holding 23 of the eligible derivations. Two additional awards
have passed peer review and await final approval in funding
within the next few weeks. These awards will fund the
expansion, the testing, the quality assurance, and the
distribution of the cells through the process I just explained.
We are also working with stem cell sources to address the
complex issues that might limit widespread availability of
these lines, in particular intellectual property issues. In the
past year, NIH has negotiated agreements with four stem cell
providers to allow both our intramural researchers access to
their cells and also to allow extramural researchers to have
access to these cells. Under these four agreements, six
intramural laboratories at NIH have received cells to pursue
research, and the agreements commit the four providers with
whom we have signed agreements to offer these cells under
similar terms to extramural investigators.
WARF, for example, which is the source that has been the
first to be able to provide cell lines has informed us that it
has agreements in place with 111 researchers and has shipped
cells to 74 of them. These researchers represent 61
institutions, 12 of them in foreign countries.
Another source, ES Cell International, informs us that it
currently has a supply of cells that far exceeds current
demand. We are still in active discussions with all sources to
be able to provide additional cell lines.
We are receiving investigator-initiated research grant
applications from new investigators. So far five new grants,
totaling $4.2 million, have been awarded. We have issued 32
administrative supplements to existing grant awards that allow
30 researchers from 25 different institutions to incorporate
research on human embryonic stem cells as part of their ongoing
federally supported research. This means that currently funded
laboratories are extending their work to include human
embryonic stem cells, which is a way for them to develop the
skills and expertise needed in this field.
Senator Specter. Dr. Zerhouni, I am reluctant to interrupt
you, but if you could sum up now, we would appreciate it.
Dr. Zerhouni. I will.
I formed a stem cell task force as soon as I arrived at
NIH, and the reason I did is because I felt that it was very
important for NIH to promote this field as fast as we can both
in terms of embryonic and adult stem cell research. I have
appointed Dr. Jim Battey as head of the Stem Cell Task Force,
and I am looking forward to continue, as aggressively as we
can, the development of this work. Thank you.
[The statement follows:]
Prepared Statement of Dr. Elias Zerhouni
Mr. Chairman, Senator Specter, and Members of the Subcommittee, I
am pleased to appear before you today to testify about the role of NIH
in advancing the field of stem cell research. Properly harnessed, adult
and embryonic stem cells have the potential to replace cells that are
damaged or diseased to restore vital functions of the human body. They
offer the promise of curing disease and ending disabilities at some
point in the future. So there are ample reasons for excitement about
stem cell research, and high expectations for new treatments are
understandable. But such expectations should be tempered by the
enormous challenges that must be addressed before the research evolves
into proven therapy.
These challenges involve both human embryonic stem cell research
and adult stem cell research. Human embryonic stem cells and adult stem
cells have potential as future therapies. I believe that NIH should
continue to fund research on both types of cells.
We are at a very early stage of embryonic stem cell research, and
have a great deal of basic research to conduct before we can unlock the
potential of these cells and fulfill their promise. I will describe the
pathway of discovery that I believe will unfold as the research evolves
from stem cell lines to cell based therapy. In the basic research
phase, which is the current focus of NIH-supported activities, we first
need to build the scientific capacity. As is true for any area of
research, progress depends on attracting outstanding scientists to
design and perform the needed studies. NIH is providing opportunities
for the scientific community to develop training courses for
researchers to acquire the skills needed to culture embryonic stem
cells, as well as opportunities to support stem cell research career
pathways. NIH has already taken major steps to accomplish this goal by
supporting infrastructure awards to expand cell lines, refine culture
methods, and establish improved methods to select the most desirable
embryonic stem cell populations.
There have been significant scientific discoveries in the past year
involving embryonic and adult stem cells. Scientists have recently
shown that human embryonic stem cells can be directed to develop into
cells resembling nerve cells, cardiac muscle cells and insulin
producing cells. These are the cells that might someday be used to
treat Parkinson's disease, heart disease and type I diabetes.
In addition to the new research opportunity provided by the
availability of human embryonic stem cells, NIH continues to
aggressively support research on developing the therapeutic potential
of adult stem cells. Scientists have recently discovered that adult
stem cells in animals may be used to repair cartilage and bone damaged
by injury and disease. In addition, research published this past summer
showed that adult stem cells from the bone marrow of both rodents and
humans can differentiate into multiple cell types, and can grow for
long periods of time in culture. Understanding the molecular signals
that direct adult stem cell differentiation may lead to new strategies
for harnessing the power of a person's adult stem cells to replenish
specialized cells destroyed by disease or aging. But it is clear that
much more research needs to be done to explore the characteristics of
adult stem cells, and to develop methods of expanding different
populations of adult stem cells in the laboratory. In addition, for
many types of adult stem cells, more research is needed to determine
techniques to expand these cells in the laboratory, a capacity that
will enable both basic and clinical studies using adult stem cells. NIH
continues to believe that research on both embryonic stem cells and
adult stem cells must be pursued simultaneously in order to learn as
much as possible about the potential of these cells to treat human
disease.
These findings are important, but I continue to emphasize that we
are at a very early stage. Much more basic research needs to be done.
Stem cell researchers have shown that these cells have long term
viability, with no evidence for genetic changes. However, human
embryonic stem cells tend to be unstable and must be closely monitored
to maintain them in their undifferentiated state. Much more basic
research needs to be done to validate the long term stability of human
embryonic stem cells, both in culture and after transplantation.
Embryonic stem cells have the remarkable capacity to continue to grow
indefinitely in an unspecialized state. In research involving other
cell types, much has been learned about key regulators of cell
division. Additional research is needed to determine how to harness the
molecular systems that control this process, so that once transplanted,
the specialized cells developed from embryonic stem cells do not revert
back to their embryonic state and grow in an uncontrolled fashion
leading to tumors or other unwelcome outcomes.
If we are able to direct stem cells to develop into a specialized
cell type, research will need to be done to determine that the
specialized cells function appropriately in the context of an animal
model system for human disease. NIH's long term commitment to
developing such animal models for diseases such as diabetes,
Parkinson's disease, and spinal cord injury will be an important factor
in developing this aspect of embryonic stem cell research. As we
proceed, NIH will also ensure that federal funds are used to support
research that has scientific merit and demonstrates outstanding
opportunities.
Such basic research is only the first phase of the journey along
the pathway of embryonic stem cell research. There are many pre-
clinical studies, which do not involve human subjects, that need to be
performed before any new therapeutic modality advances to clinical
trials on real patients. These studies include tests of the long term
survival and fate of transplanted cells, cell dosing studies, as well
as tests of the safety, toxicity, and effectiveness of the cells in
treating animal models for disease.
Trials using human subjects, the clinical research phase, will
begin only after the basic and pre-clinical foundation has been laid.
This foundation will minimize any chance of unpredictable harmful
effects that stem cell based therapies might cause. These trials are
usually phased, with the phase I trial focusing on safety, and phase II
and III trials aimed at establishing optimal dose, providing additional
assurance of safety, and determining efficacy. Only after these many
important steps are taken will the promise of embryonic stem cells to
treat disorders like diabetes, Parkinson's disease, spinal cord injury,
and cardiac failure be realized.
Having provided you with a strategic vision for research using
human embryonic stem cells, I want to explain to you how NIH is
addressing two immediate major issues that are essential for stem cell
research community to move forward:
increasing the number of stem cell researchers
As is the case at the beginning of any new field of discovery,
there is a shortage of researchers with expertise in stem cell
research. This dearth is currently a rate-limiting step in advancing
the progress of embryonic stem cell research. Simply growing embryonic
stem cells to the state where they can be used for experimentation
requires substantial knowledge, training and experience. NIH will
strive to make stem cell research as attractive as possible to our most
talented research scientists, whose creativity in developing
investigator-initiated research will move the research agenda forward.
NIH is soliciting grant applications to support training courses to
teach investigators how best to grow stem cells into useful lines.
making human stem cells more available for research
On November 7, NIH published a registry of derived stem cells that
would be eligible for federal funding. The registry consists of 14
sources across the world. The cells are in various stages of
characterization and preparation for research applications. There are
many steps required to develop embryonic stem cells from when they are
first removed from an embryo and put in culture into an established,
well characterized embryonic stem cell line ready for distribution to
the research community. After derivation, embryonic stem cells need to
be expanded from a small cluster into hundreds of million of cells
before they are ready for distribution. During the scaling up process,
investigators need to repeatedly check that the cells maintain their
ability to divide continuously and become all of the specialized cells
required for research. This process of expanding a cell line requires
time, resources, and expertise.
As a first step toward overcoming this challenge, NIH has announced
five infrastructure grant awards, totaling $4.3 million, to five
sources on the NIH Registry holding 23 of the eligible derivations. Two
additional awards passed peer review and await final approval and
funding within the next few weeks. These awards will fund the
expansion, testing, quality assurance and distribution of cells.
We are also working with stem cell sources to address complex
issues that might limit widespread availability of these eligible
cells. In the past year, NIH has negotiated agreements with four stem
cell providers to allow our intramural researchers access to their
cells. These providers have also agreed to offer similar terms to our
grantees, enabling them to obtain cells without developing their own
agreements de novo. Under these four agreements, our intramural
researchers are free to publish their findings and the NIH will own any
inventions made in the course of its research. As a result of these
agreements, six intramural laboratories have received stem cells and
are pursuing research with them. The agreements commit the four
providers to offering cells under similar terms to NIH's extramural
investigators. In addition, the Wisconsin Alumni Research Foundation
(WARF), which holds key patents on this technology, has agreed to
provide a free license to non-profit researchers conducting academic
research with cells from other providers. WARF has informed us that it
has agreements in place with 111 researchers, and has shipped cells to
74 of them. The researchers represent 61 institutions, 12 of them in
foreign countries. Another source, ESI, informs us that it currently
has a supply of cells that far exceeds current demand. Meanwhile, NIH
is in active discussions with other sources listed on the NIH Registry
in pursuit of additional agreements.
NIH is beginning to receive investigator-initiated research grant
applications from new investigators focusing on human embryonic stem
cell research. So far, five new grants, totaling $4.2 million, have
been awarded. Also, NIH has issued 32 administrative supplements to
existing grant awards that will allow 30 researchers from 25 different
institutions to rapidly incorporate research on human embryonic stem
cells as part their ongoing federally-supported research. This means
that currently funded laboratories are extending their work to include
human embryonic stem cells, which is a way for them to develop their
skills with these difficult cells and develop some preliminary data--
both key steps to success in future research. All told, over 40
investigators are now funded by the NIH to work in this area.
Much progress has occurred in the past year, including new
discoveries, identifying sources of stem cells, negotiating access
agreements, and creating a friendly environment to attract researchers.
However, these are only initial steps. To move us into the next phase,
I have created a new stem cell task force at NIH, led by Dr. James
Battey, the Director of the National Institute on Deafness and Other
Communication Disorders. The task force will provide direction for the
future in the form of recommendations for NIH-supported research
initiatives. Currently, the task force is reviewing the state of the
science for all stem cell research, with the goal of using NIH
resources to enable the scientific community to capitalize on this new
and challenging opportunity.
NIH would not be able to move forward in stem cell research, and
for that matter, any other research, without the support of this
Subcommittee. Thank you for your support. I look forward to working
with you to advance this and all fields of biomedical research. I will
be happy to answer any questions you might have.
Senator Specter. Thank you very much, Dr. Zerhouni. A
little more time was allowed for your presentation because of
the importance of what NIH is doing in setting the stage for
our other witnesses.
Since there are two votes, as I had said earlier, at 10:30,
we are going to proceed now--if you would keep your seat, Dr.
Zerhouni--to hear from the other five panelists, and then we
will proceed to questions. So if Senator Deborah Ortiz would
step forward, along with Dr. Civin, Dr. Daley, Dr. Pedersen,
and Dr. Schatten, we will hear your testimony.
STATEMENT OF SENATOR DEBORAH ORTIZ, SIXTH STATE
DISTRICT, CALIFORNIA STATE SENATE
Senator Specter. Our first witness on this panel is Senator
Deborah Ortiz, elected to the 6th State Senate District in
California in November 1998. She is the Chair of the Health and
Human Services Committee and a member of the Education, Budget,
Public Employment and Retirement, and Natural Resources and
Wildlife Committees. She received her undergraduate degree from
the University of California at Davis and her law degree from
McGeorge School of Law.
As noted earlier, if we do not conclude by 10:40, we will
have about a 30-minute break for the vote. So we are going to
try to proceed to conclude at that time.
Senator Harkin could not be here today. He is the chairman
and I am ranking. We traded positions last year. Senator
Jeffords arranged that.
But we have had a very close collaboration, and as far as
the operation of this subcommittee is concerned, it does not
make any difference whether Senator Harkin is the Chair or I
am. We have worked that closely.
Senator Ortiz, thank you very much for coming all the way.
We look forward to your testimony. This is a clock showing 5
minutes, if you could please sum up and stop by the red light.
Ms. Ortiz. Wonderful. Thank you, Senator Specter, as well
as other members of the committee. I thank you for inviting me
here. I am very conscious of running a committee on time, so I
am going to pull out my watch and try to adhere to the 5-minute
rule as well.
Thank you for inviting me to join you today at today's
hearing as you pursue the very important question and the task
of examining the implementation of President Bush's stem cell
research policy and the impact of that policy on the
development of stem cell technologies.
Let me begin by sharing with you why California found it
imperative to move forward on stem cell research. In order to
do so, let me share with you my personal history.
I served as assemblywoman and was elected to the State
Assembly in 1996. As I was transitioning in my newly elected
position as assemblywoman, my mother had been diagnosed with
ovarian cancer. I took very seriously the task of saving her
life. As I did my research and as her disease progressed, I
began to understand that as important as chemotherapy and
treatments like chemotherapy are in the lives of millions of
cancer patients and the families who take care of those
individuals, I knew that the next level of cure for cancer, as
well as all the other diseases that we are all absolutely
committed to curing and improving the quality of life, that the
real cure really resided at a very basic level in the research,
and stem cell research was offering that promise.
When President Bush declared the August 2001 64-line
limitation for use in access to Federal dollars, I decided that
I was going to try to have California move forward, and it
became even more compelling this last spring as we began to see
a couple of competing measures move through Congress. The
Brownback bill posed the greatest concern to California, not
just in its limitations and its criminalization of science and
medicine, but also in the likelihood that there would be some
success in his closing the door to science and technology and
preventing the delivery of that promise to all of those
Americans, over 100 million, who suffer from these diseases.
We also saw Senator Feinstein's work, and I thank the
members of this committee for having often a nonpartisan debate
about a very important policy issue. We were hopeful that that
bill would, indeed, become law and would preclude the Brownback
bill from becoming law. That was not to happen.
So as we moved forward in California, I hosted two
significant hearings, one in Stanford with the brightest and
most brilliant of minds, and Dr. Pedersen to my right here was
good enough to videotape his testimony and welcome us from
England and share with us why he left the United States in
order to pursue the science that we all hope to achieve in
California.
Out of that hearing at Stanford, we decided to move forward
and go to the Salk Institute and also have a hearing in which
Hans Keirstead, who is doing some incredible research in Irvine
in California, demonstrated the mice whose spinal columns had
been severed in which the introduction of stem cells produced
movement and function in the lower limbs of those mice. We also
heard the testimony from Jerry Zucker, the father of the 14-
year-old daughter with juvenile diabetes, who shared with us
his hope that his daughter would be able to live to see
adulthood and not spend her life on dialysis and ultimately die
at a very early age.
California decided to move forward in this research. I
introduced the bill that would legalize in California stem cell
research with the appropriate ethical and IRB review, as well
as prohibitions for sale and transfer of embryos.
When we broadened that commitment to curing cancer, we
acted decisively to pursue stem cell research in California. My
law that the Governor has now signed has made, for all intents
and purposes, the Bush policy on stem cell research irrelevant
in the State of California. California will move forward to
cure cancer, as well as Alzheimer's, as well as ALS, as well as
Parkinson's, juvenile diabetes, address the spinal cord injury
challenges and day-to-day realities of persons who live with
those injuries. And we will move forward. We hope to share
those therapies and that medical science and improvement with
the rest of the country.
We ask that Congress respect California's will to protect
Californians and assure that that right will be protected and
not preempted by any subsequent Federal law.
California is moving forward because we understand our
responsibility to pursue technology that promises to cure or
effectively treat over 100 million Americans. To commit the
necessary resources to deliver that hope, we have an
unavoidable obligation to do everything we can do to realize
the potential of stem cell research.
Once again, California is moving forward. We ask you to
respect that. We believe that the Bush policy is not only
medically and scientifically unsound, it is simply irrelevant
in the State of California.
Thank you.
Senator Specter. Thank you very much, Senator Ortiz.
STATEMENT OF ROGER PEDERSEN, Ph.D., DEPARTMENT OF
SURGERY, CAMBRIDGE UNIVERSITY
Senator Specter. We turn now to Dr. Roger Pedersen, a
leading stem cell researcher, who had been at the University of
California in San Francisco until September of last year. At
that time, Dr. Pedersen decided to relocate to the University
of Cambridge where he could receive government funding for his
research on human embryonic stem cells. Currently Dr.
Pedersen's research is supported by the United Kingdom Medical
Research Council and the Wellcome Trust. He received his Ph.D.
in biology from Yale.
We very much appreciate your coming such a long distance to
join us to add your own views and insights. The necessity for
your moving out of the United States is a matter of grave
concern and is obviously a factor in determining what our
policy should be as to stem cells. Dr. Pedersen, the floor is
yours.
Dr. Pedersen. Senator Specter, thank you very much for the
opportunity to speak.
As you know, until this time last year, I worked at the
University of California, San Francisco, where I had been a
faculty member for the previous 30 years and where we derived
two of the novel embryonic stem cell lines on the NIH registry
early last year. I now live and work in the United Kingdom
where I am engaged in stem cell research at the University of
Cambridge. In addition to having responsibilities for my own
research team in the Department of Surgery there, I lead a
consortium of 25 researchers who are focusing their individual
groups on various aspects of stem cell biology and medicine. I
also provide advice to other administrators and scientists in
the United Kingdom who are guiding the development of the UK
stem cell enterprise.
I would like to add my enthusiasm for how exciting this is
as the time for stem cell researchers. We are building on more
than 20 years of experience using mouse embryonic stem cells
for genetic studies and on even greater experience using human
blood stem cells for clinical treatments. This has provided a
foundation for the successful culturing of human embryonic stem
cells and opened the opportunity to control the development of
human cells in the laboratory into forming a variety of useful
tissues.
Importantly, we now have evidence that Dr. Zerhouni has
mentioned from NIH researchers that mouse embryonic stem cells
can be cultivated to produce insulin in mice and to alleviate,
in other studies, the symptoms of Parkinson's in rats. These
advances in stem cell biology raise our expectation for
clinical benefits from stem cell medicine.
All of us know of a courageous person like Christopher
Reeve who could benefit from such novel therapies. For me, it
was my mother who died of diabetes in 1989, yet still provides
me with an enduring will to help people with that disease. How
can we achieve the clinical promise of stem cell research on
their behalf?
Against these expectations, the pace of discovery of human
embryonic stem cells seems painfully slow. The lack of any
Federal support for research on human embryos, stretching all
the way from 1978 to the present day, has undoubtedly delayed
the benefits of research to infertile patients. And the long
wait for Federal funding to support stem cell research has, I
think, equally delayed the benefit of research to patients with
degenerative diseases. I admit to having been frustrated myself
with the length of time we had to wait for Federal funds for
stem cell research. Admittedly, the establishment last summer
of an NIH registry of human embryonic stem cells eligible for
Federal funding was a significant first step in advancing such
research.
However, given the length of time required to build a
successful research program, any concern on the part of
researchers for a worsening in the present U.S. policy for stem
cell funding would tend to keep prospective researchers on the
sidelines. Such concerns would definitely undermine efforts to
recruit additional researchers, particularly junior
investigators, into the field. It would be particularly
devastating if the U.S. Senate moved to criminalize the use of
somatic cell nuclear transfer to generate immune-matched stem
cells. And in this respect, it is very good to see my home
State of California has made clear its position in support of
this and all other aspects of stem cell research.
How could the Federal Government do a better job of
supporting stem cell research?
First, let me offer my respect for the will and
perseverance that the NIH has shown during the last decade in
their desire to support the fields of human embryology and
embryonic stem cells. I believe that their approach of building
up the research infrastructure by supporting training of
researchers and the standardization, characterization, and
distribution of the human embryonic stem cell lines on the
registry will prove to be a wise one for this country. I am not
convinced that it is necessary to convert the present
decentralized stem cell bank to a centralized repository.
Rather, I think that such a move by the NIH would lead to
additional delays in the accessibility of cell lines.
Therefore, my advice to them is to hold their present course.
But the truth is that the Federal Government as a whole
must make a far larger commitment in order to realize the
larger promise of stem cell medicine. New embryonic stem cell
lines must be derived and characterized in order to meet
current tissue standards for transplantation. Extensive studies
are needed to define the conditions for generating large
numbers of stem cell types from stem cell lines. Preclinical
studies in animals, including not only rodents but also non-
human primates, will be essential. And finally, careful
clinical trials in appropriate patient populations will be
needed to prove the efficacy of stem cells as medicines. This
will all take some years to achieve. I do not believe that
miracles that endure happen overnight.
To sum up my views, I believe what is needed is a long-term
U.S. commitment to develop the public policies and to sustain
the public funding that will make the stem cell dream come
true. Why should we regard the ravages of disease as
inevitable? If there is a war to be fought, surely it is
against the presently untreatable diseases which kill thousands
of people each day of the year. To mount an effective campaign
against such diseases will require a coordinated international
effort that harnesses the strength of each country. Any
abdication on this front will likely cede the present U.S.
leadership in the field of stem cells to Europe, Australia, or
Asia, together with the economic benefits which will flow
toward those countries that invest early and consistently in
stem cell biology.
prepared statement
In closing, Senator, I would like to take this opportunity
to thank you and Senator Harkin for your enduring support for
this field, not only for stem cell biology and medicine, but
also for all those who suffer from diseases. Thank you for
hearing my views.
[The statement follows:]
Prepared Statement of Roger A. Pedersen
Honorable Senators Specter and Harkin, Distinguished Colleagues,
and Guests: My name is Dr. Roger Arnold Pedersen. Until this time last
year, I worked at the University of California, San Francisco, where I
had been a faculty member for the previous 30 years, and where we
derived two novel human embryonic stem cell lines early last year. I
now live and work in the United Kingdom, where I am engaged in stem
cell research at the University of Cambridge. In addition to having
responsibilities in Cambridge for my own research team in the
Department of Surgery, I lead a consortium of 25 researchers there who
are focusing their individual groups on various aspects of stem cell
biology and medicine. I also provide advice to other administrators and
scientists in the United Kingdom who are guiding the development of the
UK stem cell enterprise.
Now is an exciting time for stem cell researchers. We are building
on more than 20 years of experience using mouse embryonic stem cells
for genetic studies and on even greater experience using human blood
stem cells for clinical treatments. This has provided a foundation for
the successful culturing of human embryonic stem cells, opening the
opportunity to control the development of human cells in the laboratory
into a variety of useful tissues. Importantly, we now have evidence
that mouse embryonic stem cells can be cultivated to produce insulin in
mice, thus alleviating the symptoms of diabetes, and to form cells that
alleviate Parkinson's symptoms in rats. These advances in stem cell
biology raise our expectations for clinical benefits from stem cell
medicine. All of us know of a courageous person, like Christopher
Reeves, who could benefit from such novel therapies. For me it was my
mother, who died of diabetes in 1989, yet still provides me with an
enduring will to help people with that disease. How can we achieve the
clinical promise of stem cell research on their behalf?
Against these expectations, the pace of discovery with human
embryonic stem cells seems painfully slow. The lack of any federal
support for research on human embryos--stretching all the way from 1978
to the present day--has undoubtedly delayed the benefits of research to
infertile patients. The long wait for federal funding to support stem
cell research has delayed the benefits of research to patients with
degenerative diseases. I admit to having been frustrated myself with
the length of time we had to wait for federal funds for stem cell
research. Admittedly, the establishment last summer of an NIH registry
of human embryonic stem cells eligible for federal funding was a
significant first step in advancing stem cell research. However, given
the length of time required to build a successful research program, any
concern for a worsening in the present U.S. policy for stem cell
funding would tend to keep prospective researchers on the sidelines.
Such concerns could definitely undermine efforts to recruit additional
researchers--particularly junior investigators--into the field. It
would be particularly devastating if the U.S. Senate moved to
criminalize the use of somatic cell nuclear transfer to generate
immune-matched stem cells. In this respect, it is good see that my home
State of California has made clear its position in support of this and
all other aspects of stem cell research.
How could the federal government do a better job of encouraging
stem cell research? First let me offer my respect for the will and
perseverance that the NIH has shown during the last decade in their
desire to support the fields of human embryology and embryonic stem
cells. I believe that their approach to building up the research
infrastructure by supporting training of researchers and the
standardization, characterization and distribution of the human
embryonic stem cell lines included on the stem cell registry will prove
to be a wise one for this country. I am not convinced that it is
necessary to convert the present ``decentralized'' stem cell bank to a
centralized repository. Rather, I think such a move by the NIH would
lead to additional delays in accessibility of cell lines. Therefore, my
advice for them is to hold their present course.
But the truth is, the federal government as a whole must make a far
larger commitment in order to realize the larger promise of stem cell
medicine. New embryonic stem cell lines must be derived and
characterized in order to meet current tissue standards for
transplantation. Extensive studies are needed to define the conditions
for generating large numbers of specialized cell types. Pre-clinical
studies in animals, including not only rodents but also non-human
primates, will be essential. Finally, careful clinical trials in
appropriate patient populations will be needed to prove the efficacy of
stem cells as medicines. This will all take some years to achieve.
Miracles that endure don't usually happen overnight.
To sum up my views, I believe what is needed is a long-term United
States commitment to development of public policies and sustenance of
public funding that will make the stem cell dream come true. Why should
we regard the ravages of disease as inevitable? If there is a war to be
fought, surely it is against the presently untreatable diseases, which
kill thousands of people each day of the year. To mount an effective
campaign against such diseases will require a co-ordinated
international effort that harnesses the strength of each country. Any
abdication on this front will likely cede the present U.S. research
leadership in the stem cell field to Europe, Australia or Asia. The
economic benefits of stem cell medicine will flow towards those
countries that invest early and consistently in stem cell biology.
In closing, I would like to take this opportunity to extend my deep
appreciation to both of you, Senator Specter and Senator Harkin, for
your enduring and unequivocal support, not only for stem cell biology
and medicine but for all those who suffer from diseases. Thank you for
hearing my views.
Senator Specter. Thank you very much, Dr. Pedersen.
Senator Murray.
OPENING STATEMENT OF SENATOR PATTY MURRAY
Senator Murray. Mr. Chairman, I am sorry to interrupt, and
I have to get to a markup. If I could just ask Dr. Zerhouni one
really critical question.
Senator Specter. Of course, Senator Murray. Proceed.
Senator Murray. I really appreciate your holding this
hearing. I think many of us were very concerned about the
President's decision to limit stem cell lines a year ago and
are watching with interest that California has now move ahead
on this and are very concerned what will happen in our States
with perhaps a drain of researchers and where that will go.
But I just wanted to quickly ask Dr. Zerhouni if State
funds are used for embryonic stem cell research, will
researchers in California or any other States that enact laws
like this receive NIH funds in the future, or will they be
prohibited from receiving those funds?
Dr. Zerhouni. No. They can receive NIH funds if they work
on the eligible cell lines that President's policy has
identified as eligible for Federal funding. There will be no
problem, and we have put in place the appropriate steps so that
an investigator could work with Federal funding on eligible
cell lines and work with State funding on other cell lines as
desired, as currently is allowed. There is no change from what
we have today.
Senator Murray. Thank you, Mr. Chairman. I have a number of
other questions I would like to submit for the record.
Senator Specter. Of course, Senator Murray, they will be
accepted for the record and responses will be made.
Dr. Pedersen, let me thank you for your good words for
Senator Harkin and myself.
We had set upon a program to double NIH funding. We have
moved it from $12 billion to $23 billion. This year we have in
our budget $3.7 billion in addition. But there has to be a
bill. So far we have not had any legislation come out of the
appropriations process, and if we are to have a continuing
resolution, that means that the funding will probably stay
level. That will be very, very bad for many projects, but
especially for NIH where we will have done more than the
doubling which we had anticipated. From $12 billion, it would
put us at $26.7 billion.
I make that comment at this time so that all of those here
can use your lobbying influences to help us get a bill, and if
you want a more particular road map, I would be glad to talk to
you later.
STATEMENT OF GERALD SCHATTEN, Ph.D., PROFESSOR OF CELL
BIOLOGY, UNIVERSITY OF PITTSBURGH,
DIRECTOR, PITTSBURGH DEVELOPMENT CENTER,
AND DEPUTY DIRECTOR, MAGEE-WOMEN'S RESEARCH
INSTITUTE
Senator Specter. We will turn now to Dr. Gerald Schatten,
deputy director of Magee-Women's Research Institute and
director of the Pittsburgh Development Center. He is a
professor and vice chair of obstetrics, gynecology and
reproductive sciences and cell biology at the University of
Pittsburgh School of Medicine. He received his Ph.D. from the
University of California at Berkeley.
I have worked with you and, we are glad to have you in
Pennsylvania, Dr. Schatten. It seems to me we have got a very
heavy California influence here today.
The floor is yours.
Dr. Schatten. Thank you, Senator Specter, and it is a great
pleasure for me to have this opportunity to speak with you.
The NIH deserves tremendous commendations for their efforts
in rapid implementation this past year, but serious and
substantial work remains. From my own experiences, I need to
voice grave concerns about the current Federal stem cell
policies because it is already hindering invaluable research,
undermining the wisest investments, and delaying the day when
we will know for sure whether human embryonic stem cells can be
used to treat diseases.
The NIH's registry lists 71 lines. Science reports only 16
are available. My search has identified just a handful. As of
last Thursday, we have just two.
We need accuracy and clarity. Perhaps 71 lines do meet
eligibility criteria, but just being eligible is not the same
as available.
To obtain approved lines, I have traveled to Europe and
Asia to collaborate with scientists in Korea, Singapore,
Australia, Sweden, and the UK. They are willing and motivated.
But should American science not also be conducted on American
soil?
NIH has sponsored my research for the last 25 years, and we
investigate how fertilization succeeds and how the embryo
develops. Last November, we were among the first to apply to
investigate how human embryonic stem cells divide and
proliferate. When cells lose chromosomes, they can develop into
cancers. If human embryonic stem cells lose chromosomes when
they are put into a patient's body, as Dr. Zerhouni mentioned,
they could develop into cancers. Chromosome movements in human
embryonic stem cells must be accurate and that is just what we
are doing in our laboratory.
Researchers at the Pittsburgh Development Center of Magee-
Women's are discovering that embryos form very differently
between the mammals cloned successfully by somatic cell nuclear
transfer and primates, as investigated in monkeys. Cloned cows
and mice can develop without any sperm contributions, whereas
primates, in which all somatic cell cloning attempts have
failed so far, appear to depend on a unique complementation
between the egg's machinery and the sperm's special structures.
Reproductive cloning in humans is dangerous, unethical,
unjustified, and for biological purposes we would predict that
it will fail.
Therapeutic cloning, on the other hand, in which embryonic
stem cells are produced in a plastic dish in the absence of any
sperm or any fertilization event, promises unique methods to
overcome our body's own immune rejection systems. The editorial
this week in Science entitled ``Harmful Moratorium on Stem Cell
Research'' is authored by some of the hand-picked members of
the President's own Bioethics Panel.
Last April, NIH modestly funded our proposal for just a
year. These supplements are insufficient in time or amount for
the best research programs to justify redirection. The NIH must
be more aggressive in supplementing investigator-initiated
grants with significant funding. Cooperative agreements would
enlarge the talent pool. New equipment is necessary to ensure
the separate of stem cell research from ongoing activities.
Labs selected for multi-year awards should also be responsible
for research training.
Commercial-academic cooperations also need to be encouraged
further.
On Sunday, I met with Lans Taylor, who is CEO of the
Pittsburgh-based company Cellomics. He has mocked up human
embryonic stem cell pluripotency kits and assays to determine
whether these lines will develop into neurons. Other companies
could further reduce the hurdles very swiftly if they were
encouraged to jump into this field and reduce the research
hurdles.
During this hearing, we have discussed national policy and
contrasted it with stem cell rules elsewhere. We are the United
States and each State has its own laws and restrictions that
may prove enabling or restrictive. Senator Specter, you know
well that our Commonwealth of Pennsylvania has language
restricting human embryonic stem cell research. The Abortion
Control Act of 1989, written long before stem cells were
discovered, prohibits embryonic research.
Homeland Security Director Tom Ridge, while still Governor
of Pennsylvania, decided that cells derived outside of
Pennsylvania were eligible for research within our
commonwealth.
We have heard just now from Senator Ortiz that California
is enacting laws to enable human embryonic stem cell studies.
It may be within this subcommittee's purview that in
addition to witnessing American scientists emigrating, we may
soon see U.S. scientists relocating from States with ambiguous
laws to other States.
Senator Specter, subcommittee members, I applaud you and
others in Congress for your unwavering support of the NIH. Your
sponsorship and encouragement of healthy Federal and private
sector competition produced the human genome sequence under
budget and far sooner than expected. When we decided to
decipher the genome, which also generated controversies, we
deliberated thoughtfully and invested adequately.
More and better lines are needed now and current policies
are already delaying stem cell research, forcing it off shore
or into inaccessible reaches in the private sector.
prepared statement
Would Galileo have been satisfied if he could have looked
at 65 or 71 stars? Maybe, but he would not have discovered our
place in the solar system unless Jupiter traveled through that
narrow field.
In today's terms, the cost of the Hubble telescope and all
of NASA is the same if our focus is restricted or if we are
permitted to explore the heavens.
Thank you.
[The statement follows:]
Prepared Statement of Dr. Gerald Schatten
Good morning, Chairman Harkin, Senator Specter, and other
distinguished Subcommittee Members. I'm Gerald Schatten, Professor of
Cell Biology at the University of Pittsburgh and Director of the
Pittsburgh Development Center.
The NIH deserves commendation for their efforts and rapid
implementation this past year, but serious and substantial work
remains. From my experiences, I need to voice grave concerns about the
current federal stem cell policy because it's already hindering
invaluable research, undermining the wisest expenditures and delaying
the day when we'll know whether stem cells can be used to treat
diseases.
The NIH's Human Embryonic Stem Cell Registry lists 71 lines.
SCIENCE reports only 16 are available. My search has identified just a
handful right now--as of last Thursday, we've received two.
We need accuracy and clarity. Perhaps 71 lines meet eligibility
criteria, but just being eligible isn't the same as available.
To obtain approved lines, I've traveled to Europe and Asia to
collaborate with scientists in Korea, Singapore, Australia, Sweden and
the UK. They're willing and motivated . . . but American science should
also be conducted on American soil.
NIH has sponsored my team's research for the past twenty-five years
and we investigate how fertilization succeeds and how the embryo forms.
Last November, we were among the first to apply to investigate how
human embryonic stem cells divide and proliferate. When cells lose
chromosomes, they can develop into cancers. Chromosome movements must
be accurate in HESCs for safe transfer to patients, or new cancers
might arise--and that's what we're working to understand and prevent.
Researchers at the Pittsburgh Development Center are discovering
that embryos form very differently between the mammals cloned
successfully by somatic cell nuclear transfer (SCNT) and primates, as
investigated with monkeys. Cloned cows and mice can develop without any
sperm contributions, whereas primates, in which all SCNT cloning
attempts have failed so far, appear to depend on the unique
complementation of the egg's essential machinery with special sperm's
structures.
Reproductive cloning in humans is dangerous, unjustified and
unethical.
Therapeutic cloning, in which embryonic stem cells are produced in
a plastic dish in the absence of any sperm or fertilization event,
promises unique methods to overcome our body's natural immune rejection
systems. The editorial this week in SCIENCE entitled ``Harmful
Moratorium on Stem Cell Research'' is authored by some of the
handpicked members of the President's Bioethics Panel.
Last April NIH modestly funded our proposal for just one year.
These supplements are insufficient in time or amount for the best
research programs to justify redirection. The NIH must be more
aggressive in supplementing investigator-initiated grants with
significant, not token, funding. Cooperative agreements would enlarge
the pool of talented labs. New equipment is necessary both to ensure
the separation of HESC research from on-going lab activities and also
because the tests for pluripotency and differentiation are specialized.
Labs selected for multi-year awards could be responsible for research
training.
Commercial-academic cooperation needs to be encouraged further. As
one example, I asked Lans Taylor, CEO of Cellomics to mock up
pluripotency, growth and differentiation assays. Pittsburgh-based
Cellomics and other companies could further reduce research hurdles
quickly.
During this hearing, we've discussed our national policy and
contrasted it with stem cell rules elsewhere. We are united States--and
each state has its own laws and regulations that may prove enabling or
restrictive.
Senator Specter knows well that our Commonwealth of Pennsylvania
has language restricting HESC research. The Abortion Control Act of
1989, written long before HESCs were discovered, prohibits embryonic
research.
Homeland Security Director Tom Ridge, while still Governor of
Pennsylvania, decided that cells derived outside of Pennsylvania were
eligible for research within our commonwealth.
We've all read that California is enacting laws to enable HESC
studies.
It is may be within this subcommittee's purview that in addition to
witnessing American scientists emigrating, we may soon also see U.S.
scientists relocating from States with ambiguous laws to other States.
Mr. Chairman, Senator Specter, Subcommittee Members, I applaud you
and others in Congress for your unwavering support of NIH--your
sponsorship and encouragement of healthy federal and private sector
competition produced the human genome sequence under budget and sooner
than predicted. When we decided to decipher the Genome, which also
generated controversies, we deliberated thoughtfully and invested
adequately.
More and better lines are needed now and current policies are
already delaying stem cell research, forcing it offshore or into
inaccessible reaches in the private sector.
Would Galileo have been satisfied if he could have looked at 59 or
71 stars? Maybe, but he wouldn't have discovered our place in the Solar
System unless Jupiter traveled through that narrow field.
In today's terms, the cost of the Hubble telescope and all of NASA
is the same if our focus is restricted, or if we're permitted to
explore the heavens.
Thank you.
Senator Specter. Thank you, Dr. Schatten. Dr. Schatten, you
are safe in Pennsylvania. Do not move.
STATEMENT OF CURT CIVIN, M.D., PROFESSOR OF CANCER
RESEARCH, SIDNEY KIMMEL COMPREHENSIVE
CANCER CENTER, JOHNS HOPKINS UNIVERSITY
Senator Specter. We turn now to Dr. Curt Civin, King Fahd
Professor of Oncology at Johns Hopkins University where he
developed a stem cell selection process which has led to the
development of more effective and less toxic cancer therapies.
Dr. Civin holds nine patents for biomedical inventions related
to stem cell research. He received his M.D. from Harvard
Medical School.
Thanks for joining us, Dr. Civin, and we look forward to
your testimony.
Dr. Civin. Thank you, Senator Specter, Senator Hutchison,
Senator Ortiz. Thank you for the honor of testifying before you
today.
I am very grateful for this committee's strong and
consistent support for lifesaving biomedical research. It is
also a special privilege for me to testify today with my friend
and former Johns Hopkins colleague, Elias Zerhouni. Our Nation
is indeed privileged to have a scientist of his distinction and
capability serve as NIH Director.
I am professor of Cancer Research at the Johns Hopkins
University School of Medicine, where I hope to stay. My
clinical specialty is caring for children with cancer and this
motivates my research. For the past 23 years, I have studied
adult stem cells, mainly human bone marrow stem cells that can
reconstitute our blood and immune systems. I discovered the
CD34 stem cell molecule that allows identification and
isolation of these rare blood-forming stem cells. The discovery
is widely used in stem cell research and in clinical bone
marrow transplantation, and two companies have licensed related
inventions. And so I want to disclose to you that Johns Hopkins
University and I have a financial interest in certain stem cell
inventions and medical therapies.
Today my research continues to focus on adult stem cells.
We need to figure out how to grow these stem cells easily and
in large numbers so that, for example, a bone marrow donation
from one single donor can provide enough stem cells for
multiple transplant patients.
The 1998 discovery of human embryonic stem cells
significantly raised our hopes of solving this therapeutic
problem. By studying these cells, we hope to discover the
molecular pathways by which they can proliferate without
differentiating and then figure out how, in effect, to push the
same molecular buttons in adult stem cells. Such discoveries
would enhance the treatment of my cancer patients and might
also help in the development of stem cell regenerative medical
therapies for the range of other diseases.
President Bush's decision to allow federally funded
research on a qualified number of human ES stem cell lines
increased our hopes of advancing this research. The decision
has, however, proved much more limited than we anticipated.
More than a year after the President's announcement, I am still
waiting to receive my very first stem cell line. In fact,
embryonic stem cell research is crawling like a caterpillar.
Few human embryonic stem cell lines exist and most are not
truly available. A number of the lines on the NIH stem cell
registry have been tied up in questions of ownership. Many of
the owners of the not-in-dispute cell lines are not anxious to
share them with other researchers. Those that are willing to
share their lines expect a piece of the profits on future
discoveries. The terms of material transfer agreements are
often difficult and time consuming to negotiate. The owners
also expect an up-front fee. The going rate is $5,000, an
amount 50 to 100 times greater than what we are accustomed to
paying for a cell line.
Besides these administrative burdens, there are significant
technical challenges as well. Little is known about the cell
lines themselves. Without this information, individual
researchers are essentially flying blind. We must characterize
the cell lines ourselves, an extraordinarily inefficient use of
limited resources.
An example. Last fall, a colleague applied to receive the
best studied of the cell lines on the initial NIH list, the H1
cell line from Wisconsin. Six months later he received the
cells. It took him more than 4 months to grow enough ES cells
to perform even preliminary experiments. These cells grow
exceedingly slowly, one-tenth the rate of the cells we usually
work with.
For my research, I need several ES cell lines since I am
sure that not all will form blood cells or will grow rapidly.
Last fall I was contacted by a company in India which owns
seven of the embryonic stem cell lines on the NIH registry.
They wanted to collaborate with my lab to explore the blood-
forming potential of these lines. I spent several months
negotiating collaboration and materials transfer, but the
imminent agreement was abruptly canceled in May. The company
told me that the Indian Government had put an indefinite hold
on sending ES cell lines out of their country.
In July I applied for a different ES cell line from
Wisconsin that is reported to grow somewhat faster than H1 and
to form some blood cells. I have been told that because of
technical problems with these cells, I will not receive them
until October at the earliest.
Stem cell research has tremendous potential to deliver
treatments and cures. With research we can make stem cells that
are self-renewing, that are less likely to be rejected by the
recipient's immune system and that regenerate tissues and
organs fully.
Today the United States of America is the best place in the
world to do all biomedical research. I do not want us to lose
that lead in stem cell research. And we are really in danger of
doing so. Without our vigorous leadership in federally
supported research in this country, the worldwide pace of
discoveries will be much slower than necessary. Instead of
being the first in line to benefit from new treatments as they
are now, our patients in America will have to wait. We will
lose talent to other nations, as you have heard, and new jobs
and industries will be spawned elsewhere.
Every week we read about exciting new stem cell research
underway in other countries. Prime Minister Tony Blair of the
UK recently said he wants Britain to be the best place in the
world for stem cell research. Singapore has invested $1.7
billion. I am heartened by Dr. Zerhouni's recent creation of
the NIH Stem Cell Task Force and look forward to its
contributions. Much work needs to be done.
Mr. Chairman, I am also, again, grateful to the
subcommittee for including language here in your fiscal year
2003 committee report directing NIH to take positive steps to
stimulate research. Specifically I would strongly endorse your
language, urging NIH to develop a stem cell repository. A
repository would promote research and lower the barriers to
obtaining stem cell lines for investigators like me. Under this
arrangement, NIH would characterize the lines and then act as a
technical resource and distribution center. This would
eliminate duplication of effort and provide an invaluable
technical resource for growing the cells.
prepared statement
Once again I want to thank you for your commitment to
biomedical research and for your assistance in clearing
unnecessary impediments to progress. You have really made a
difference. Thank you.
[The statement follows:]
Prepared Statement of Dr. Curt I. Civin
Chairman Harkin, Ranking Member Specter, and members of the
Subcommittee thank you for the honor of testifying before you today
about the hurdles that I, and many other, scientists have experienced
in attempting to conduct embryonic stem cell research in the wake of
President Bush's decision last year to permit research on a qualified
number of stem cell lines. I am very grateful for your strong and
consistent support of biomedical research and your interest in
promoting life-saving stem cell research. I am also grateful for the
language included in your fiscal year 2003 Committee Report directing
NIH to take a number of positive steps to stimulate stem cell research.
I am Professor of Cancer Research at the Sidney Kimmel
Comprehensive Cancer Center of the Johns Hopkins University School of
Medicine. My clinical specialty is caring for children with cancer, and
this motivates my laboratory research on normal and leukemic stem
cells. For the past 23 years, I have studied adult stem cells, mainly
the stem cells from human bone marrow that can reconstitute our blood
and immune systems after intensive radio-chemotherapy in a bone marrow
transplant. I am best known scientifically for discovery of the CD34
stem cell molecule that allows identification and isolation of these
rare blood-forming stem cells. The CD34 monoclonal antibody is widely
used in stem cell research as well as clinical bone marrow
transplantation, and for this I received the National Inventor of the
Year Award in 1999. Thousands of patients have received successful bone
marrow stem cell transplants, mainly to mediate the toxic effects of
their cancer therapy, but also for diseases such as immune
deficiencies, autoimmune disorders, and aplastic anemia. Two companies
have licensed related inventions, and so I must disclose to you that
Johns Hopkins University and I have a financial interest in certain
stem cell research and medical therapies.
Today, my research continues to focus on adult stem cells. Despite
our successes, over 15 years of intense investigations on adult blood-
forming stem cells has not taught us all we need to know about the
biology of these adult stem cells. For example, we need to figure out
ways to grow these cells easily and in large numbers so that like yeast
in a fermenter a marrow donation from one donor could be expanded to
provide stem cells for multiple bone marrow transplant recipient
patients. The problem is that, outside of the body, these blood-forming
stem cells rarely proliferate without differentiating. That is, the
stem cells divide into more mature progeny that are no longer stem
cells.
So I was excited by the 1998 discovery of human embryonic stem
cells (hES) that can expand indefinitely in tissue culture without
losing their capacity to generate stem cells of many types of organs
and tissues. Our hope is to study these embryonic stem cells, discover
the molecular pathways by which they can proliferate without
differentiating, and then figure out how, in effect, to push the same
molecular buttons in adult stem cells. Such discoveries would enhance
the treatment of my patients with cancer, by using transplants of adult
stem cells taken from bone marrow. In addition, the lessons from this
research might also help in the development of stem cell regenerative
medical therapies for a range of other diseases. Note that the ultimate
goal of my research is to facilitate the use of adult stem cells in the
clinic by studying embryonic stem cells in the laboratory.
In the years 1998-99, I was able to study a single line of human
embryonic germ cells that was derived at Johns Hopkins. I had to be
exceedingly careful not to use any federal funds to do these studies.
Corporate agreements slowed and limited extensive experiments.
Unfortunately, our research did not find the key to unlock the
mechanisms that could turn this cell line into blood-forming cells. One
possible reason is that this cell line seemed to have a predilection to
develop into nerve, not blood cells. I then needed to obtain several
other cell lines for further studies. Federal policy decisions in 2000/
2001 appeared to allow me to do this. However, these guidelines were
put on hold in early 2001, until President Bush announced the current
guidelines in August 2001, more than a year ago.
The President's decision renewed our hopes of pursuing this
therapeutic research. NIH's initial list of stem cell lines that could
be used in federally funded research seemed like a straightforward
source of available resources. However, we quickly found out that none
of these cell lines was available readily to us. That remains true
today.
In fact, embryonic stem cell research is crawling like a
caterpillar. While NIH has listed more eligible lines on its registry
(http://escr.nih.gov/), only a tiny fraction of these lines are
accessible--and only to those persistent and patient enough to jump
through a series of hoops and endure lengthy waits. I am still waiting
to receive my first stem cell line.
The difficulties are numerous. As recent news articles have
reported, and my experience has shown, some of the lines have been
tied-up in questions of ownership. Many of the owners of lines, not in
dispute, are not anxious to share them with other researchers. Those
that are willing to share the lines, are not willing to do so without
getting a piece of the profits of future discoveries made using the
lines. The terms of material transfer agreements are often difficult
and time-consuming to negotiate. The owners also expect an upfront fee.
The going rate is $5,000--an amount 50-100 times greater than the $50-
$100 we are accustomed to paying for a cell line.
While the administrative burdens necessary to obtain stem cells
from NIH's list of eligible lines are tremendous and the costs
significant, little is known about the lines themselves. Without this
information, individual researchers are essentially flying blind. They
must characterize the lines themselves and determine through a painful
process of trial and error whether any line will advance their
research. This is an extraordinarily inefficient use of limited
resources.
The best studied of the cell lines on the initial NIH-approved list
was the H1 cell line from Wisconsin. A colleague of mine applied to
receive these cells in fall, 2001. Finally six months later, after
complex material transfer negotiations and a $5,000 payment, he
received the cells. Having cleared the administrative and financial
hurdles, the next problem he confronted was technical. These cells grow
exceedingly slowly, one-tenth the rate of the cells we usually work
with. So it has taken my colleague more than four additional months of
incremental steps until he has been able to grow enough ES cells to
perform even preliminary experiments.
I need several ES cell lines, since I suspect from prior experience
that not all will form blood cells, or grow rapidly. In Fall 2001,
Reliance Life Sciences, a company from India contacted me. One of
Reliance's scientists had been the Ph.D. mentor for a current
postdoctoral fellow in my lab, and he knew our work well. Seven of the
ES cell lines on NIH's current list of 81 approved hES cell lines are
owned by Reliance, and they wanted to collaborate with my lab to
explore the blood-forming potential of these cell lines. I spent
several months negotiating collaboration and materials transfer, but
the imminent agreement was abruptly cancelled in May 2002. The company
told me that the Indian government had put an indefinite hold on
sending human ES cells out of their country.
Another ES cell line from Wisconsin, called H9, is reported to grow
somewhat faster than H1, and to form some blood cells. Having learned
in June 2002, that H9 cells would be available in July, I applied for
this cell line. I completed the now simpler material transfer forms,
and paid my $5,000, but I have been told that because of some technical
problems with the H9 cells, I will not receive them until October, at
the earliest. I look forward to these experiments, but despair of being
able, in the near future, to obtain or afford multiple ES cell lines
for the research I would like to do.
My experience obtaining stem cells from NIH's approved list is not
unique. This paper chase for stem cell lines has stunted the field of
stem cell research. Most investigators need multiple hES cell lines.
Few hES cell lines exist, and most are not truly available. In fact, it
is my understanding that only the cells from Wisconsin and, as of just
last week, one cell line from the University of California, San
Francisco are available to scientists who are neither collaborators of
the companies nor investigators who derived the lines. Only a few
federal grants are trickling out for stem cell research. The review of
a grant application is always rigorous. Scientist peer-reviewers demand
that the applicant demonstrate experience with the cells and model
systems proposed, and some strong preliminary results showing that the
concepts proposed for investigation are not just wishful thinking. This
has served as a Catch-22 for many scientists who want to study human ES
cells, since the human ES cell lines they need simply to begin their
research are few and costly, they grow very slowly, and the available
cell lines may not be able to function as needed, as in my case to
develop blood, or other specific tissue types.
Many scientists have similar stories to tell, and you will hear
from several eminent ones today. We all believe that stem cell research
has tremendous potential to deliver treatments and cures. I believe
that the pressure should be on us, as stem cell researchers to turn
that potential into treatments for our patients. With research, we can
make stem cells that are self-renewing, that are less likely to be
rejected by the recipient's immune system, and which regenerate a
variety of engineered tissues and organs that might even perform better
than the originals. As a scientist, I want to get started. I want to
bring these benefits to my patients and others. I do not want to limp
along. I want other scientists to enter this field. I want to be
spurred on by their advances.
Today, the USA is the best place in the world for every field of
biomedical research. I do not want us to lose that lead in stem cell
research--and we are in danger of doing so. Without our vigorous
leadership in federally supported stem cell research, the pace of
discoveries will be much slower than necessary. Instead of being the
first in line to benefit from new treatments developed at home,
Americans will have to wait. We will lose talent to other nations. And,
new jobs and industries will be spawned elsewhere.
Every week, we read about exciting new stem cell research underway
in countries, many of which have not been known, historically, as
leaders in biomedical research. The list includes China, Singapore,
Australia, and the U.K. The Financial Times reports that Prime Minister
Tony Blair wants to make Britain the ``best place in the world'' for
stem cell research, so that ``in time our scientists, together with
those we are attracting from overseas, can develop new therapies to
tackle brain and spinal cord repair, Alzheimer's disease, and other
degenerative diseases such as Parkinson's.'' \1\ Singapore shares these
ambitions. The Economist reports that the Asian nation seeks to become
a magnet for stem cell research. In the last two years alone, it has
invested $1.7 billion in efforts to attract global talent and industry
and build its infrastructure to support stem cell research.\2\
---------------------------------------------------------------------------
\1\ ``The stem of competitiveness,'' The Financial Times, August
30, 2002.
\2\ ``Send in the clones,'' The Economist, August 24, 2002 U.S.
Edition.
---------------------------------------------------------------------------
I believe it is our nation's responsibility and indeed in our
interest not to let the discoveries, the treatments and cures, and the
jobs that stem cell research will someday provide move overseas. We
need to pursue all promising avenues of stem cell discovery. U.S.
scientists need better access to human embryonic stem cells to continue
to lead the field of stem cell research.
I am heartened by NIH Director Elias Zerhouni's recent creation of
a Stem Cell Task Force and look forward to its contributions to the
field. Much work needs to be done to reduce administrative and
technical barriers and to encourage more scientists to pursue this
vital research.
I also strongly endorse your fiscal year 2003 Committee Report
language on stem cell research, urging NIH to develop a stem cell
repository. Such an initiative would promote research by lowering the
costs--in both time and money--of obtaining stem cell lines. Under this
arrangement, NIH would characterize the cell lines, and then act as a
technical resource and distribution center for scientists seeking to
obtain them. This would eliminate duplication of effort and provide an
invaluable technical resource for growing the cells. Vesting one
organization with the ability to distribute all cell lines would also
produce economies of scale.
Once again, Mr. Chairman and members of the subcommittee, I want to
thank you for your commitment to biomedical research and for your
assistance in clearing unnecessary impediments to progress.
Thank you very much, Dr. Civin.
STATEMENT OF GEORGE DALEY, M.D., Ph.D., ASSISTANT
PROFESSOR OF MEDICINE, HARVARD MEDICAL
SCHOOL; AND FELLOW, WHITEHEAD INSTITUTE FOR
BIOMEDICAL RESEARCH
Senator Specter. Our next witness is Dr. George Daley,
assistant professor of Medicine at Harvard and a fellow at the
MIT-affiliated Whitehead Institute where he studies stem cells
of the blood. His research has helped define the molecular
basis for human leukemia and provided insights into normal
blood development. Prior to his appointment at Harvard, Dr.
Daley served as chief resident in medicine at Massachusetts
General Hospital. His Ph.D. is from MIT and his M.D. is from
the Harvard Medical School.
Welcome, Dr. Daley. We look forward to your testimony.
Dr. Daley. Thank you, Chairman Specter, distinguished
members of the subcommittee.
My name is George Daley. I am a faculty member at Harvard
Medical School and I run a research laboratory at the MIT-
affiliated Whitehead Institute that studies stem cells that the
body uses to form blood. This has prompted our intense interest
in using human embryonic stem cells for our research. My
laboratory currently holds NIH grants to support research on
both mouse and human embryonic stem cell biology.
My laboratory has spent the last 7 years using mouse ES
cells to investigate how blood cells develop in the Petri dish.
Recently our group has taken a step forward. We successfully
transplanted mice with blood stem cells derived entirely from
mouse embryonic stem cells. Then, in collaboration with my
colleague, Rudolf Jaenisch, we performed an important first
demonstration of therapeutic cloning to treat a mouse with a
genetic immunodeficiency, similar to the Bubble-boy disease.
Our team plucked a cell from the tail of an afflicted mouse,
used nuclear transfer to create an ES cell line, used gene
therapy to correct the genetic defect, and then performed blood
stem cell transplants into diseased mice. The repaired ES cells
provided a source of immune cells and antibodies in the treated
mice.
Encouraged by this first proof of principle in an animal
model, my team is eager to apply the same strategy to human ES
cells. Our hope is that one day the process will be efficient,
safe, and effective for treating patients with a variety of
genetic and malignant bone marrow diseases.
However, over the past year, the progress of my own team
and I would say that of the research community in general has
been palpably slowed, in part because of the frustrating lack
of access to human ES cells and in part due to the restrictive
nature of the President's funding policy as mandated in his
address of August 9, 2001.
I wish to make three points.
First, the biomedical research community needs more cell
lines. While the President announced that over 60-odd lines
were available, it has become increasingly clear over the past
year that far fewer lines have been characterized adequately,
perhaps only a handful.
Second, the research community needs a central repository
for ES cell lines, preferably in a facility funded by NIH, that
would provide free access to a comprehensive set of carefully
maintained and documented lines for research.
Third, I wish to emphasize that the Federal funding
guidelines are currently so restrictive that they are already
threatening this fledgling, yet highly promising field of
research.
First, my personal experience. My team was one of the first
in the United States to gain access to the ES cells that Jamie
Thomson and his colleagues derived at the University of
Wisconsin. However, since obtaining that single cell line in
mid-2000, we have been frustrated in attempts to obtain
another. One week ago, after nearly 2 years of inquiries with a
number of other research groups, we finally received our second
line.
Why did it take so long? Well, the number of laboratories
interested in working with these cells is increasing
explosively. This dictates that a more effective means must be
established for the distribution of these valuable reagents. I
believe that a central warehouse and processing facility should
be established and funded by the NIH. A central repository
would maintain consistent, standard operating procedures for
the culture and maintenance of the cell lines.
Finally, I want to comment on the state of research on
human embryonic stem cells after a year under the policy
announced by President Bush last August. I would applaud
President Bush for his principled stance in favor of human ES
cell research. Having access to even a few well-characterized
human ES cell lines enables us in the research community to
begin to address generic questions about ES cell biology.
However, this is only the beginning and the current policy will
not enable the research community to follow through with the
work needed to treat patients. President Bush made the right
call in allowing Federal funding for research, but his policy
excludes some of the most important and promising new avenues.
As I have stated, it is unclear precisely how many cell
lines exist, but I strongly believe that the number is far
fewer than listed on the NIH registry.
Second, the President's policy does not allow support for
deriving new cell lines which is of tremendous scientific
interest.
My last point, the President's policy does not allow for
studies of ES cell lines derived by nuclear transfer. This is
currently the most appealing avenue for creating ES cells from
patients with specific diseases and for creating ES cell lines
that are genetically matched to patients. Our research team
showed that nuclear transfer methods can be applied in the
practice of therapeutic cloning in mice. I have no doubt that
legitimate and successful medical treatments in real patients
will be developed sooner if the Federal Government funds
nuclear transfer studies with human ES cells starting today.
The sad and undeniable truth is that the existing restrictions
are keeping these advances from being realized.
prepared statement
In conclusion, I would say that the field of ES cell
research is in a fragile state at best under the current
presidential policy. The current policy represents a half-
hearted effort to support this revolution in biology and
threatens to starve the field at a time when greater
nourishment is critical. It is a testimonial to the passion of
the young scientists that come to my lab who are so driven by
the enormous potential of ES cells that they are willing to
work diligently despite the uncertainties intrinsic to the
current policy. It is the spirit of scientific passion and
enthusiasm, combined with a truly generous financial commitment
to health care research by our Federal Government that has made
American science and our health care system the envy of the
world. As a Nation, we should not miss the opportunity to
nurture and invigorate this exciting field of medical research.
Thank you.
[The statement follows:]
Prepared Statement of Dr. George Q. Daley
Distinguished members of the subcommittee. Thank you for the
opportunity to address you this morning.
My name is George Daley. I am an Assistant Professor of Medicine at
Harvard Medical School, a Research Fellow at the MIT-affiliated
Whitehead Institute, and a staff hematologist at the Massachusetts
General Hospital and the Children's Hospital in Boston. I run a
research laboratory that studies stem cells that the body uses to form
blood. We aim to understand how blood stem cells become deranged in
diseases such as leukemia as well as to understand how normal blood
cells develop within the embryo. This has prompted our intense interest
in using human embryonic stem cells--ES cells--in our research.
My laboratory has spent the last seven years using mouse ES cells
to investigate how blood cells develop in the Petri dish. Recently our
group has taken a step forward. We successfully transplanted mice with
blood stem cells derived entirely from mouse ES cells. Then, in
collaboration with my colleague Rudolf Jaenisch, we performed an
important first demonstration of therapeutic cloning to treat a mouse
with a genetic immune deficiency similar to the Bubble-boy disease. Our
team plucked a cell from the tail of an afflicted mouse, used nuclear
transfer to generate an ES cell line, used gene therapy to correct the
genetic defect, and then performed blood stem cell transplants into
disease mice. The repaired ES cells provided a source of immune cells
and antibodies in the treated mice. Encouraged by this first proof-of-
principle in mice, my team is eager to apply the same strategies to
human ES cells. Our hope is that one day the process will be efficient,
safe, and effective for treating patients with a variety of genetic and
malignant bone marrow diseases.
However, over the past year the progress of my own team and of that
of the research community has been palpably slowed, in part because of
the frustrating lack of access to human ES cells, and in part due to
the restrictive nature of the President's funding policy as mandated in
his address of August 9, 2001.
I will make three points. First, the biomedical research community
needs more cell lines. While the President announced that over 60-odd
cell lines were available as of August 9, 2001, it has become
increasingly clear that far fewer lines have been characterized
adequately. Some two thirds of the cell lines are located outside of
the United States, and most are controlled by commercial entities.
Currently, only a handful of lines are available to U.S. scientists.
Second, the biomedical research community needs a central
repository for embryonic stem cell lines, preferably in a facility
funded by NIH, that would serve the needs of the research community as
a whole, providing free access to a comprehensive set of carefully
maintained and documented human ES lines for research.
And third, I wish to emphasize that the federal funding guidelines
are currently so restrictive that they are already threatening this
fledgling yet highly promising field of biomedical research.
First, my personal experience. My team was one of the first in the
United States to gain access to the human ES cells that Jamie Thomson
and his colleagues derived at the University of Wisconsin. However,
since obtaining a single line of cells in mid-2000, we have been
frustrated in attempts to obtain additional lines. Many experiments
require comparing the behavior of several different embryonic stem cell
lines, since the behavior of any single line may be atypical and
therefore highly misleading. One week ago, after nearly two years of
inquiries with number of other research groups, we finally received a
second cell line.
Why did it take so long? What are the hurdles that hinder sharing
of these critically important research tools? What might be done to
remedy the situation? The issues are complex. It is human nature that
some scientists might wish to preserve their monopoly over these
valuable cell lines. However, an accepted norm within our field, and a
stipulation for publishing in most if not all journals, is that all
research reagents will be made readily available to the research
community to enable research results to be replicated and extended.
Typically, when we request a research tool from a colleague in the
research community, we receive it immediately, especially in this era
of email and FEDEX. For all but a small handful of human ES cell lines
listed on the NIH registry, this simply is not happening.
There is the perception that human ES cells hold significant
commercial value given their potential for yielding products. Companies
control most of the lines, and they have worked aggressively to
dominate the intellectual property that flows from these cells. Thus,
protracted negotiations over Material Transfer Agreements--called
MTAs--have slowed the sharing of these lines with the wider research
community. One of the most valuable initiatives performed by the U.S.
Public Health Service and the NIH since August 9, 2001, was to
negotiate with the University of Wisconsin a Memorandum of
Understanding that provides a common set of terms for all federally
funded researchers.
We have spent significant effort over the last two years
negotiating MTAs with four different groups. Our most recent experience
is a testimonial on how these negotiations should and can work. One of
my post-doctoral scientists met Dr. Meri Firpo of the University of
California, San Francisco, at a scientific meeting in August. Dr. Firpo
had received a grant from the NIH to build an infrastructure to
disseminate the lines, and graciously agreed to expedite our request.
Our MTA negotiations were simplified by the prior agreements that had
been hammered out by the NIH. Exactly 8 days ago, only some 6 weeks
after originally speaking with Dr. Firpo, we received a second strain
of human embryonic stem cells. We also received a handbook of detailed
recipes for growing and maintaining the cells, and data on the
characterization of the cell line. Clearly, Dr. Firpo is providing an
exceptional service and her behavior should become a standard for how
valuable embryonic stem cell lines are distributed to the scientific
community.
The number of laboratories interested in working with these lines
is already large and is increasingly explosively. This dictates that a
more effective means must be established for the distribution of these
valuable research reagents. I believe that a central warehouse and
processing laboratory should be established and funded by the NIH to
facilitate greater access to human ES cell lines for the general
community of biomedical researchers. A central repository would
maintain consistent standard operating procedures for the culture and
maintenance of the cell lines. Strict quality control parameters would
be established, and cell lines would be faithfully characterized under
a uniform set of conditions. The Medical Research Council of the UK has
just announced that it would fund such an effort in that country.
Finally, I wish to comment on the state of research on human ES
cells after a year under the policy announced by President Bush last
August 9, 2001. I would applaud President Bush for his principled
stance in favor of human ES cell research. Having access to even a few
well-characterized human ES cell lines enables many of us in the
research community to begin to address generic questions about ES cell
biology. We can make advances in cultivation of the cells, in coaxing
the cells to become blood cells, neurons, insulin-producing cells, and
the like. But this work is only the beginning, and the current policy
will not enable the research community to follow-through with the work
needed to treat patients. President Bush made the right call in
allowing Federal funding for research, but his policy excludes some of
the most important and promising avenues, and critical features of the
policy are tying the hands of the research community.
First, the President announced that research support would be
tendered only for cell lines that pre-existed before August 9, 2001. As
I have stated, it is unclear precisely how many cell lines exist but I
strongly believe that the number is far fewer than listed on the NIH
registry. The President's policy prevents U.S. scientists from
exploiting new cell lines as they become available. Scientists are by
their very nature innovators, and hungry for the latest, most up-to-
date technology and tools. All human ES cells listed on the NIH
registry were derived in contact with mouse feeder cells. Scientists
throughout the world are actively seeking to develop new cell lines
that avoid this contamination, and would therefore be more valuable for
generating human therapies. Indeed, scientists from Singapore have
published the derivation of lines free of mouse cell contamination, but
under the current policy, U.S. scientists can not study these cells
using federal funds.
Second, the President's policy does not allow support for deriving
new cell lines, which is of tremendous scientific interest. This is in
stark contrast to the United Kingdom, whose scientists have made many
of the seminal discoveries in ES cell biology and given their greater
freedom are poised to dominate further. Our research community, hobbled
by current restrictions, is falling behind researchers in other
countries that are racing ahead to take full advantage of the
possibilities that embryonic stem cells offer.
Third, the President's policy does not allow for studies of ES cell
lines derived by nuclear transfer. This is currently the most appealing
avenue for creating ES cells from patients with specific diseases, and
for creating ES cell lines that are genetically matched to patients,
which would overcome immune rejection of transplanted ES cell products.
Our research team showed that nuclear transfer methods can be applied
in the practice of therapeutic cloning in mice. I have no doubt that
legitimate and successful medical treatments in real patients will be
developed sooner if the Federal government funded nuclear transfer
studies with human cells today. The sad and undeniable truth is that
the existing restrictions are keeping these advances from being
realized.
I realize that funding for some of these initiatives is currently
prohibited by federal statute and that a change in legislation to
specifically allow this work is needed. I applaud you Senator Specter,
in your efforts to propose such legislation.
In conclusion, I would say that the field of human ES cell research
is in a fragile state at best under the current Presidential policy.
The current policy represents a half-hearted effort, and threatens to
starve the field at a time when greater nourishment is critical. The
scientists who come to train in my lab voice concerns that they might
face inadequate research support in the future. It is a testimonial to
the passion of these young scientists, who are so driven by the
enormous potential of ES cells that they are willing to work diligently
despite the uncertainties inherent under the current policy. It is that
spirit of scientific passion and enthusiasm--combined with a truly
generous financial commitment to health care research by our Federal
government, that has made American biomedical science and our health
care system the envy of the world.
Here at the beginning of the 21st century, we stand at the
threshold of a new era in biomedicine, when cells will be harnessed to
treat a wide array of degenerative conditions in an aging society. As a
nation, we should not miss the opportunity to nurture and invigorate
this exciting field of biomedical research.
Thank you for your time and interest in this matter.
Senator Specter. Thank you very much, Dr. Daley.
Dr. Zerhouni, we start with you on the questioning. You
heard the testimony about the sharp limitations on the
availability of stem cell research lines. In the fall of last
year when NIH assembled the stem cell registry, it listed 78
stem cell lines from 14 sources around the world. According to
the information which our subcommittee has been able to glean,
only five of these lines are available to stem cell
researchers. NIH has awarded, as you testified, $4.3 million in
infrastructure grants to five companies and institutions with
23 eligible stem cell lines. Of these five companies, we are
told only four have signed material transfer agreements with
NIH, and these four companies have only 17 eligible stem cell
lines. Of these 17 stem cell lines, only 5 have been shipped
and are available to researchers.
Would you start the clock? We are going to have 5-minute
rounds.
The question is, is there a sufficient number of stem cell
lines available for the required research?
Dr. Zerhouni. Well, in terms of the number of eligible
lines which is, as you said, 78, and the number of lines
available for wide distribution, we would agree that over the
year there has been an increasing number of lines. Last spring
there was one. This month there are five. As far as we can tell
from talking to all the suppliers, there are 10. I went over in
my opening statement the time line that it takes to go from an
eligible line that is just derived to a widely available
distributable line.
So I think that progress is being made and we are, as
mentioned by some of the researchers, diligently working with
as many sources as we can to make more lines available.
Senator Specter. You are working with the sources of the 78
lines which were approved by the President as of August 9.
Dr. Zerhouni. Correct.
Senator Specter. And the question is, is that adequate? I
know you are bound by the administration's decision, but the
Congress has the authority to legislate in the field. The
President may veto it but we can override a veto by two-thirds.
In the spring of 2000, when NIH funding was not available on
all of the stem cell research, Senator Harkin, myself, and
others started a move, and we had letters signed by 64 Senators
disagreeing with the Federal policy on stem cells. I had
personal commitments from 12 more who were unwilling to put it
in writing, but assured me that they would support legislation
in the field.
Then the President came out with his compromise position.
In essence, on August 9, and immediately after that, there was
a flurry of publicity as to whether those lines were adequate.
And the indications were at that time that they were not.
After September 11, all of the oxygen has been sucked out
of Washington on virtually every other subject until Iraq came
along to take some precedence. And we have been waiting to see
the developments and have deferred this hearing, but now we are
going to be faced with a decision as to what to do next.
So it is a pretty blunt question as to whether the existing
stem cell lines are adequate. You have heard your colleagues at
the table. What do you think?
Dr. Zerhouni. My feeling is that we are at a very early
stage. It is actually not knowable how many lines you will need
to advance the field. In other comparable fields, very often
researchers want to limit the number of well-characterized
lines that are used for experimentation.
So I would say at this moment, I do not think we know the
answer. We need to work and develop more researchers and more
laboratories that are going to experiment with the lines that
we want to make available to find that answer. I really do not
know the answer.
Senator Specter. Well, Dr. Zerhouni, when will we know? Can
you give me a time line as to when we will know?
Dr. Zerhouni. We will work as diligently as we can to make
as many lines available to as many laboratories. There is no
limit to the funding that we can direct to the laboratories
that present good, solid research proposals.
Senator Specter. Dr. Pedersen, to what extent do you think
your example will be followed by others, in leaving the United
States to go to places like Great Britain where you can get
funding on stem cell research?
Dr. Pedersen. I cannot answer that exactly, Senator, but we
are working as diligently as possible to recruit them.
Senator Specter. Have you had any success?
Dr. Pedersen. How I would like to answer that is in part a
response to your prior question, which is how many cell lines
are available to do the necessary work and how many are needed.
There are, I think, adequate numbers of existing cell lines to
do a portion of the work, the portion that will be focused on
in the United States with Federal funding, namely, the
characterization of the steps needed to get useful, specialized
cells. So the dozen or so that are currently available,
actually available probably are sufficient to do that.
I think this number issue is a red herring, though, because
to go into patient care, the existing lines are not really
useful because they have all been grown with a combination of
mouse cells which makes them unsuitable for transplantation. So
the actual number of suitable lines for transplantation is zero
in the current set, and new lines must be generated. So the
clinical delivery very likely will take place elsewhere and
people who are interested in participating in that part of it
will probably have to do so elsewhere.
Senator Specter. So you are saying the number of stem cell
lines for clinical delivery, transplantation is zero.
Dr. Pedersen. On the registry is zero. There is one line
that was developed recently in Singapore.
Senator Specter. Well, that could hardly be characterized
as an adequate number.
Dr. Pedersen. And so the development of such lines in the
U.S. would require a change in policy.
Senator Specter. My red light is on, plus 39 seconds from
your last answer.
Senator Hutchison.
OPENING STATEMENT OF SENATOR KAY BAILEY HUTCHISON
Senator Hutchison. Well, thank you, Mr. Chairman, for
holding this hearing, and I thank all of you for coming.
I am very concerned about the real-life stories. I always
am interested when policies are set, and I think the
President's policy was meant to be one that would allow for
real use of the lines that are available so that we could do
the testing that is necessary. But then I hear your stories
about trying to get lines and then India does not let them out,
and then you try to get a line in another way from Wisconsin
and, yes, it is coming, well, no it is not, well, yes, it is
later. That does not seem to be working in the practical sense.
I have researchers at UT Southwestern who are very
concerned about availability. They are now doing work with
animal nerve and pancreatic stem cells. They want to further
that study, and they are very concerned about access.
So I would just ask you this question. I think that Senator
Specter asked the big question, what can we do to make it more
practically available? I think all of us are concerned about
that.
On top of that, though, I now have another concern, and
that is I have some great research institutions, M.D. Anderson,
Baylor, UT Southwestern, UT San Antonio, UT Galveston. They are
really on the cutting edge of research. Now California has
stepped forward I think in a way that could start luring some
of our good scientists to California, and I would like to ask
you this question, Dr. Zerhouni.
Now that California is looking at giving State help in this
regard and so many of our institutions are public institutions
that do get private help but also need government help, what
can we do to keep everything balanced so that all of a sudden
we do not see people migrating from Harvard and Johns Hopkins
and all these other great research institutions, including
mine, all to the west coast? I am not saying I do not wish the
west coast well. I do, but I do not want to, all of a sudden,
throw a big kink in the research world. So tell me how we can
deal with that effectively.
Dr. Zerhouni. Well, clearly I think, in terms of Federal
funding, we need to look at all the aspects of facilitation of
the research, and that is what we are doing. We have
established the Stem cell Task Force where we can get input
from the scientific community from all States as to exactly how
we can, in fact, enhance the ability of these institutions to
do the research. As Dr. Pedersen said, we need to do the basic
research before we can go to clinical research. It will take
years, but we need to do that.
In terms of State support and private support, there is
nothing in the current policy that prevents that from
happening. In California, for example, the UCSF lines were
developed in part with State help.
Senator Hutchison. I understand that, Dr. Zerhouni. I know
it is possible, but the amount that is available from private
and State funds is not comparable to what could be available
from Federal funds. So you are now looking at a potential
problem I think even though private funds can be used, but it
does become complicated, especially if you are doing a project
that has Federal funds and then you want to take the next step.
You want to go to the stem cell part that would actually show
results. Do you have to stop doing the federally funded
research?
Dr. Zerhouni. Currently we allow researchers to do side-by-
side federally funded research and non-federally funded
research in parallel. There is no NIH policy that prevents that
as long as appropriate accounting mechanisms are in place. So I
think that can still be done.
Senator Hutchison. And it can be the same, exact project.
So you are on a project and the next thing you want to do is
test it with embryonic stem cells, and you have a federally
funded project. Can you use embryonic stem cells under the
present law or the President's policy to do that research?
Dr. Zerhouni. As long as there is strict accounting of what
is used. The present policy is very clear. You cannot use
Federal funds for non-eligible lines, and you have to have in
place accounting mechanisms which are clearly spelled out in
our policies to be able to do that, but it is doable.
Senator Hutchison. I would like to ask other members of the
panel if they feel that that differentiation is enough to allow
people to go forward.
Dr. Civin. Senator Hutchison, I was thinking of a slightly
different analogy, in terms of California, when I read this in
the news, and I was hoping that Maryland would do the same
thing and that other States would follow Justice Brandeis'
suggestion I believe, that the States should be the
laboratories of democracy in this area of stem cell research
and that we should experiment with different solutions. I
happen to think that the solution from the State of California
is outstanding and would like to see that be the example for
our Federal solution that is followed by the entire Government
because this is where the money that will make the rubber hit
the road will happen.
Very little funding realistically will come from the States
for very much research. It has to be Federal funding for it to
work. Ultimately it has to be a coherent Federal policy so that
we can collaborate across the country on our research. But I
see instead California as an example of a laboratory for
democracy here.
Senator Hutchison. Dr. Schatten.
Dr. Schatten. Senator Hutchison, thank you so much for
these probing questions. I think we need to acknowledge that
Dr. Zerhouni and the entire NIH is doing absolutely everything
within their power, but it is not within their power. I know
from my own experiences that in order for us to work on eggs
that have failed to be fertilized from an IVF clinic, we need
absolutely everything to be privately funded, even million
dollar microscopes that we might use for just 10 minutes.
Many university administrators are terrified that their
full Federal funding could be withdrawn if one investigator
enters into an area that might pose a risk because of a
confusion in how funds are either mingled or not commingled. I
think really it is at this level, as Senator Specter has
mentioned, that we could benefit from a clear national policy.
Thank you.
Senator Hutchison. Thank you.
I have seen the difference that the doubling of the NIH
budget has made in the area of research, particularly into
diseases that are not prolific diseases but nevertheless need
to have research into them. I know that the availability of
Federal funding is making a huge difference in the knowledge
base that we have in medical research into so many diseases
that have been ignored in the past.
So I would just say that I think Dr. Schatten's point is
very good. I think NIH is doing everything they can. I think
they are moving forward in every possible way with the policies
that we have, but I just want to see what more we can do and
also determine if something works in practicality after it is
set forward.
I even think the President meant to do that. I think he
said we are going to try this. This is the best way to approach
it, in a very careful way, and he wanted to be careful because
he values life so much. So I know his intentions were right,
but I also think he left it open for us to come back and say--
not me, but you, the research community and you, Dr. Zerhouni--
he is going to look to you for advice to say did it work. How
can we continue progress in a way that also gives value to
human life? I think we just have to keep working on input from
the research community and creativity, which I think Senator
Specter is showing in trying to create a bank at NIH perhaps
with some of these lines to make sure that they do not get into
legalistic delays and bureaucratic stumbling that stop progress
in America.
I want this research to be done in America, and I want you
to come home.
Senator Specter. Thank you very much, Senator Hutchison.
We are now about 9 minutes into a 15-minute vote, so we are
going to have to adjourn, as I had mentioned earlier.
What I would like you to do, Dr. Schatten, Dr. Civin, Dr.
Daley, Senator Ortiz, and Dr. Pedersen, is to provide in
writing what you would like to have available. You, Dr. Daley,
talked about nuclear transfer studies. I would like to get the
specifics as to what you have in mind. Dr. Civin commented
about waiting a year for lines and he has not gotten them yet.
Dr. Schatten talked about not enough lines available and
worried about therapeutic cloning, as Senator Ortiz said.
I believe that the legislation passed by the House imposing
criminal penalties on nuclear transplantation, or so-called
therapeutic cloning, will not come to pass. We have stopped it
in the Senate. We may have 60 votes if there is time on the
calendar to pass a bill which would permit nuclear
transplantation.
I think Senator Hutchison summarized the matter well. The
President took a significant step on August the 9 in permitting
some Federal funding. He was subjected to a lot of criticism.
It is pretty hard not to be criticized on virtually anything
the President or any of us in elective office do, so we are
used to that. But then we have to see what has happened.
I would like you to respond specifically to what you would
like to see done. Senator Ortiz, you have special insights into
legislation. Give me your insights as to what legislation you
would like to see done.
My own sense at the moment is that Congress is going to
have to legislate on the subject. We had waited for a year-plus
to see the experience.
Dr. Zerhouni, if you can supplement what you have said with
a time line as to when you think you might know, we would be
interested to know that.
But I think the time has come to legislate in the field. As
I said, last year we had 64 Senators in writing and commitments
from 12 more, and 12 and 64 are 76, which is 9 more than 67. So
we are in a position to move where the need is sufficiently
great.
I think this testimony has been very, very helpful. I think
we have gotten the kernel of it, and your written answers will
give us the balance. So thank you all very much for coming in.
ADDITIONAL SUBMITTED STATEMENT
We have received the prepared statement of Senator Larry
Craig which will be placed in the record.
[The statement follows:]
Prepared Statement of Senator Larry Craig
Mr. Chairman, I would like to thank you for holding this hearing
today to spotlight stem cell research. I would also like to thank all
of our witnesses here today for taking the opportunity to address this
very complex issue.
Stem cell research continues to offer a great deal of promise. This
research could lead to exponential improvements in the treatment of
many terminal and debilitating conditions. In many cases, researchers
are already beginning to see the promise of this research.
With the President's decision last year to allow federal funds to
be used to support research on existing stem cell lines, researchers
have begun to make progress. Many scientists in this field of research
confirm that there are ample number of cell lines available to fully
understand how these cells work. We must encourage more researchers to
take advantage of this historic opportunity.
Researchers are in the early stages of this process. It is a
difficult science and should be dealt with at an appropriate pace. Many
will say that this process is moving too slowly. However, there are
many scientific hurdles that will have to be surmounted before we get
to the point of actually replacing damaged tissues in the body and
understanding the potential for clinical applications. This could take
years. But we should invest the time and resources into doing what it
takes to get to that point.
I understand that NIH has made a good-faith effort to facilitate
the use of the existing stem cell lines and has created a framework to
enable researchers to begin stem cell research in the United States.
Understanding that there are many obstacles that must be overcome
before major strides are made, we must be as supportive of this
research as possible.
Again, I thank the Chairman for holding this hearing and look
forward to learning more about the developments in this important
research.
CONCLUSION OF HEARING
Senator Specter. Thank you all very much for being here,
that concludes our hearing.
[Whereupon, at 10:45 a.m., Wednesday, September 25, the
hearing was concluded, and the subcommittee was recessed, to
reconvene subject to the call of the Chair.]
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