[Senate Hearing 111-942]
[From the U.S. Government Publishing Office]
S. Hrg. 111-942
THE PROMISE OF HUMAN EMBRYONIC STEM CELL RESEARCH
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HEARING
before a
SUBCOMMITTEE OF THE
COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE
ONE HUNDRED ELEVENTH CONGRESS
SECOND SESSION
__________
SPECIAL HEARING
SEPTEMBER 16, 2010--WASHINGTON, DC
__________
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COMMITTEE ON APPROPRIATIONS
DANIEL K. INOUYE, Hawaii, Chairman
ROBERT C. BYRD, West Virginia THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont CHRISTOPHER S. BOND, Missouri
TOM HARKIN, Iowa MITCH McCONNELL, Kentucky
BARBARA A. MIKULSKI, Maryland RICHARD C. SHELBY, Alabama
HERB KOHL, Wisconsin JUDD GREGG, New Hampshire
PATTY MURRAY, Washington ROBERT F. BENNETT, Utah
BYRON L. DORGAN, North Dakota KAY BAILEY HUTCHISON, Texas
DIANNE FEINSTEIN, California SAM BROWNBACK, Kansas
RICHARD J. DURBIN, Illinois LAMAR ALEXANDER, Tennessee
TIM JOHNSON, South Dakota SUSAN COLLINS, Maine
MARY L. LANDRIEU, Louisiana GEORGE V. VOINOVICH, Ohio
JACK REED, Rhode Island LISA MURKOWSKI, Alaska
FRANK R. LAUTENBERG, New Jersey
BEN NELSON, Nebraska
MARK PRYOR, Arkansas
JON TESTER, Montana
ARLEN SPECTER, Pennsylvania
Charles J. Houy, Staff Director
Bruce Evans, Minority Staff Director
------
Subcommittee on Departments of Labor, Health and Human Services, and
Education, and Related Agencies
TOM HARKIN, Iowa, Chairman
DANIEL K. INOUYE, Hawaii THAD COCHRAN, Mississippi
HERB KOHL, Wisconsin JUDD GREGG, New Hampshire
PATTY MURRAY, Washington KAY BAILEY HUTCHISON, Texas
MARY L. LANDRIEU, Louisiana RICHARD C. SHELBY, Alabama
RICHARD J. DURBIN, Illinois LAMAR ALEXANDER, Tennessee
JACK REED, Rhode Island
MARK PRYOR, Arkansas
ARLEN SPECTER, Pennsylvania
Professional Staff
Erik Fatemi
Mark Laisch
Adrienne Hallett
Lisa Bernhardt
Michael Gentile
Alison Perkins-Cohen
Bettilou Taylor (Minority)
Sara Love Swaney (Minority)
Jennifer Castagna (Minority)
Administrative Support
Teri Curtin
C O N T E N T S
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Page
Opening Statement of Senator Tom Harkin.......................... 1
Statement of Francis S. Collins, M.D., Ph.D., Director, National
Institutes of Health, Department of Health and Human Services.. 6
Human Embryonic Stem Cells....................................... 7
Adult Stem Cells................................................. 7
Induced Pluripotent Stem Cells................................... 8
Three Key Uses of Human ES Cells................................. 8
High-Throughput Drug Screening................................... 9
Prepared Statement of Francis S. Collins......................... 11
The Need for Additional Stem Cell Lines.......................... 23
Limitations of Adult Stem Cells.................................. 24
Importance of Federal Funding.................................... 24
Stem Cell Injunction Dictated by Doctrine........................ 26
Impact of Judicial Decisions..................................... 26
The Effect of the Preliminary Injunction on NIH Embryonic Stem
Cell Research.................................................. 27
American Recovery and Reinvestment Act (ARRA) at NIH............. 28
Advances in Embryonic Stem Cell Research......................... 29
Embryonic Stem Cells as a Research Tool.......................... 30
The Ethics of Human Embryonic Stem Cell Research................. 31
Prepared Statement of Senator Patty Murray....................... 32
Prepared Statement of Senator Dianne Feinstein................... 33
Statement of George Q. Daley, M.D., Ph.D., Director, Stem Cell
Transplantation; Associate Director, Stem Cell Program,
Children's Hospital Boston, Boston, Massachusetts.............. 34
Prepared Statement of........................................ 37
Statement of Sean J. Morrison, Ph.D., Director, Center for Stem
Cell Biology, University of Michigan, Life Science Institute,
Ann Arbor, Michigan............................................ 40
Prepared Statement of........................................ 43
Statement of Jean Peduzzi Nelson, Ph.D., Associate Professor,
Department of Anatomy and Cell Biology, Wayne State University
School of Medicine, Detroit, Michigan.......................... 45
Prepared Statement of........................................ 48
Statement of Cody Unser, Founder, Cody Unser First Step
Foundation, Washington, DC..................................... 56
Prepared Statement of........................................ 58
Autologous Stem Cell Treatment................................... 60
Additional Committee Questions................................... 61
Questions Submitted by Senator Thad Cochran...................... 62
Scientific Hurdles............................................... 62
Federal Funding.................................................. 63
International Competitiveness.................................... 63
Question Submitted by Senator Patty Murray....................... 63
Research Funding................................................. 63
Prepared Statement of the American Association for Cancer
Research....................................................... 65
The Court Injunction is a Setback for Scientific Discovery and
Cancer Research................................................ 65
Human Embryonic Stem Cell Research Holds Much Promise for Cancer
Patients....................................................... 65
AACR Supports Sound, Ethical and Responsible Stem Cell Research
Poli-
cies........................................................... 66
Prepared Statement of the Americans for Cures Foundation......... 67
Prepared Statement of the California Institute for Regenerative
Medicine....................................................... 69
National Institutes of Health (NIH) Grants for Human Embryonic
Stem Cell Research Cover Critical Work on Which CIRM/California
Research is Dependent.......................................... 69
Validating the Potential for Therapies Derived From Human
Embryonic Stem Cells........................................... 70
Type 1 Diabetes.................................................. 70
Stroke........................................................... 70
Macular Degeneration (Age-related Vision Impairment or Blindness) 70
ALS--Lou Gehrig's Disease........................................ 70
Alzheimer's Disease.............................................. 71
Prepared Statement of the Student Society for Stem Cell Research. 71
THE PROMISE OF HUMAN EMBRYONIC STEM CELL RESEARCH
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THURSDAY, SEPTEMBER 16, 2010
U.S. Senate,
Subcommittee on Labor, Health and Human
Services, and Education, and Related Agencies,
Committee on Appropriations,
Washington, DC.
The subcommittee met at 10:05 a.m., in room SD-124, Dirksen
Senate Office Building, Hon. Tom Harkin (chairman) presiding.
Present: Senators Harkin, Murray, Specter, and Cochran.
Also present: Senator Wicker.
opening statement of senator tom harkin
Senator Harkin. Good morning. The Senate Appropriations
Subcommittee on Labor, Health and Human Services, and Education
will now come to order.
Well, this is the 21st hearing that this subcommittee has
held on human embryonic stem cells starting back in December
1998, 1 month after Dr. Jamie Thompson of the University of
Wisconsin announced that he had isolated them for the first
time. And I want to note for the record that it was Senator
Specter who led this subcommittee at that time, who led the
hearings beginning then and on through the remainder of the
1990s and into the 2000s, and then when the gavel changed
hands, I picked up from him and we have kept this effort going
on. At that time, it was a very bipartisan basis. And so I just
want to acknowledge the great leadership role that Senator
Specter has played in this whole effort on embryonic stem cell
research.
It is a shame that we have to revisit this issue under the
circumstances in which we find ourselves today. When President
Obama lifted the Bush administration's restrictions on stem
cell research a year and a half ago, most of us thought the
fight was finally over. At last, we thought, there was a new
approach to scientific research in this country, one that was
dictated not by politics or ideology, but by ethical science.
At last, we thought, our brightest young minds could enter this
field without worrying that they would go to the lab one day
and find the doors ordered shut by someone in Washington, DC.
At last, we thought, we could begin to realize the promise of
embryonic stem cell research. And we were on track to do that.
The National Institutes of Health (NIH) instituted new
guidelines to ensure that this research would be conducted
ethically and responsibly. The number of stem cell lines
eligible for federally funded research rose from 21 to its
current total of 75. And the scientific community has
responded, applying for and receiving NIH grants that are
moving this research forward in robust and exciting ways.
At the same time, of course, NIH continued to fund research
on adult stem cells and on induced pluripotent cells (iPS) and
numerous other approaches to regenerative medicine that could
lead to treatments and cures.
Embryonic stem cells have very special properties that no
other cells can match, and that is why they offer so much hope
to people who are suffering. That is why so many scientists are
excited to have access to these stem cell lines and to see what
they can learn from them.
Then out of the blue came the preliminary injunction from
District Judge Royce Lamberth. That action, once again, has
placed a cloud of uncertainty over this entire scientific
field. Thanks to a temporary stay by the D.C. Circuit Court,
human embryonic stem cell research is, for the time being
anyway, progressing just as it was before Judge Lamberth's
ruling. But how long that will last is anybody's guess.
Well, I can say this. We have come too far to give up now.
If we do not win this battle in the courts, we will have to
take it up in Congress. This research must continue. The
politicians and activist judges who oppose it need to respect
the views of the overwhelming majority of the American people
who want this research to go forward. People across America--
and I am one of them--have too many loved ones and friends who
have died from ALS, from Parkinson's, from spinal cord
injuries, and other diseases that might one day respond to
treatments made possible by embryonic stem cell research.
I remember Christopher Reeve testifying before this
subcommittee several years ago. I wish we still had him around
today. I remember Rob Borsellino, a newspaper man from Iowa who
had ALS, testified before our subcommittee. I wish we had him
around still too.
As long as there is a reasonable chance that this research
could help ease human suffering and save lives, I believe we
have a moral responsibility to pursue it.
The purpose of today's hearing is to examine the promise of
human embryonic stem cell research. We will look at the
science. We will not relitigate the ongoing court case. None of
the witnesses is prepared to discuss the legal arguments for or
against the injunction. So I ask members of this subcommittee
to refrain from asking them questions that are not in their
area of expertise. And I say to our witnesses if you receive
such questions regarding legality or court decisions, you
should not feel required to answer them in any way. We want to
stick to the science, where we are in the science, what is
happening with all forms of stem cell research, what role
embryonic stem cell research is playing in that whole area
today.
So before we begin, I would like to turn to Senator Cochran
for any opening remarks he would like to offer.
Senator Cochran. Mr. Chairman, thank you very much. We
appreciate your calling this hearing, to give us an opportunity
to further explore options for the Congress in dealing with the
difficult choices we have to make in supporting research that
is so important in finding cures for illnesses.
I know when we first started looking into this area of stem
cell research, my brother-in-law was dying of leukemia. Buzzy
Clayton was one of the finest young men our State had produced,
at that time, and he just had an outstanding future and was a
wonderful person in every way. I am sure that is something that
I will always keep in mind and remember his great loss. And
there are many others like Buzzy Clayton who might benefit--we
hope would benefit--from findings that are made through
additional and more aggressive research on how to combat these
terrible illnesses.
I thank my colleague, Roger Wicker, who is here today to be
our lead-off witness in this hearing. He has been a leader in
this area for some time, and we commend him for his successes
in his efforts.
Senator Harkin. Thank you, Senator Cochran.
I say to other people on the panel if you want to
incorporate your statements into your opening questions, that
would be fine too.
But before we go to our panels, Senator Roger Wicker of
Mississippi has asked to make a brief opening statement and we
certainly welcome our colleague to this panel. Senator Wicker,
if you have a statement, it will be made a part of the record
in its entirety, and please proceed as you so desire. But
welcome.
Senator Wicker. Thank you very much, Mr. Chairman, and I
appreciate the opportunity to be back with you. As you know, I
served on the subcommittee in the House that is the counterpart
of this subcommittee, and so it is wonderful to be here today.
If I am doing something wrong on the microphone, maybe I will
be the guinea pig and it will be ready for the rest of the
panel.
I appreciate the opportunity to appear on the subject of
embryonic stem cell research. As you know, in 1995 I co-
authored an amendment to the Labor, Health and Human Services,
and Education, and Related Agencies Appropriations Act
prohibiting the use of taxpayer funds to create human embryos
for research or support any research in which human embryos are
harmed, destroyed, or subjected to risks not permitted for
unborn children. This so-called Dickey-Wicker language has
remained the law of the land for a decade and a half.
In my opinion, the body of scientific evidence developed
since 1995 has served only to strengthen the argument in favor
of Dickey-Wicker, but the basic premise for the provision has
not changed. It is this.
Number one, the destruction or cloning of human embryos for
research purposes raises profound moral and ethical challenges.
Number two, the Federal Government should not be involved
in subsidizing this controversial life-altering research with
taxpayer dollars.
Number three, there are limited Federal funds available for
health-related research.
Number four, if human embryonic stem cellresearch is to be
done at all, it should be paid for with nontaxpayer funds.
The chair mentioned Dr. James Thompson. He was the first to
isolate human embryonic stem cells and one of the scientists
who discovered the groundbreaking embryo-free way to produce
genetically matched stem cells, known as iPS cells. iPS cells
are adult cells that have been genetically reprogrammed to an
embryonic stem cell-like state. This discovery has changed the
debate on embryonic stem cells.
When discussing the ethics surrounding embryonic stem cell
research, Dr. Thompson himself said ``If human embryonic stem
cell research does not make you at least a bit uncomfortable,
you have not thought about it enough.'' Recent polling proves
that embryonic stem cell research makes many Americans
uncomfortable. According to a 2010 Rasmussen poll, 57 percent
of Americans oppose taxpayer funding of embryonic stem cell
research. In other words, the majority of Americans support the
current ban on using taxpayer dollars to fund research in which
embryos are destroyed.
The question is, if we can use adult stem cells, reprogram
them to act like embryonic stem cells, and avoid the ethical
challenges, then why would we not take that approach?
Some people would have us think that prohibiting Federal
funding of embryonic stem cell research is stopping science
entirely. I disagree. As we all know, private funds can be used
for this research and are being used for this purpose. The
distinction is whether or not the Federal Government should be
subsidizing controversial, life-altering research with taxpayer
dollars, especially when the majority of Americans oppose such
a move.
Federal funding is scarce. Indeed, because of funding
limits, we simply are unable to afford all the research we
would like to do. I submit that we should use limited taxpayer
dollars on already proven research demonstrated in areas like
adult stem cells. Adult stem cells are the ones that are
treating people right now. In fact, treatments have been so
effective that many doctors have turned to adult stem cell
transplants as a standard life-saving therapy for hundreds of
thousands of people, people suffering from dozens of diseases
and conditions, including cancer, juvenile diabetes,
Parkinson's, multiple sclerosis (MS), leukemia, lymphoma,
spinal cord injuries, and corneal regeneration, among others
are turning to adult stem cell treatments for help.
An estimated 50,000 adult stem cell transplants are
occurring annually worldwide using stem cells from bone marrow,
umbilical cord blood, and other tissues. Research with adult
stem cells has produced therapies for more than 70 afflictions
and demonstrated promising results.
Advancements in this field are happening every day. Just 3
months ago, researchers reported they had restored vision to
people whose eyes were damaged from chemicals. Doctors took
stem cells from the patient's healthy eye and multiplied them
in a lab to transplant to the damaged eye where they grew into
healthy corneal tissue.
Preclinical trials to treat spinal cord injury patients
have also proven to be promising in recent years. At age 16,
Laura Dominguez was paralyzed from the neck down in a car
accident. Doctors treated Laura for spinal cord injury using
her own nasal adult stem cells. As a result of the surgery and
extensive physical therapy, Laura has regained feeling and
movement in her lower body and she continues to make progress.
iPS research is another promising field. iPS cells are
producing unprecedented opportunities in medicine, toxicology,
and drug discoveries. All over the world, hospitals and
laboratories are developing IPSCs from individuals with various
diseases. For example, a clinic in Ontario, Canada, has already
created more than 130 IPSC lines for 11 diseases. This clinic
is also working on making lines to address diseases such as
autism and schizophrenia. If there are additional funds, Mr.
Chairman, Congress should invest in this type of groundbreaking
research.
Supporters of embryonic stem cell research would like to
ignore such accomplishments. They would suggest that providing
Federal tax dollars on embryonic stem cell research is the only
means of getting results. However, the accomplishments among
adult and pluripotent stem cells versus embryonic stem cells
prove otherwise.
I am proud to say that for a decade and a half, the Dickey-
Wicker amendment has protected life. This debate involves
profound ethical and moral questions. This is a matter of
conscience for me, but more importantly, it is a matter of
conscience for millions of Americans who are deeply troubled by
the idea that their taxpayer dollars may be used to destroy
another human life when there are other proven techniques
available.
Mr. Chairman and members of this subcommittee, I want to
thank you very much for your time, and I appreciate the
opportunity to testify on this important issue.
Senator Harkin. Senator Wicker, thank you very much for
your statement, and I know of your long-term interest in this
area. And we thank you for your appearance before the
subcommittee.
I know you have a lot of important things and you are a
busy person like everyone else, and so we thank you for being
here. Thank you for your testimony. And you are excused, if you
would like, unless you have something else you would like to
add as an emphasis point or something like that.
Senator Wicker. Thank you very much.
Senator Harkin. All right. Thank you very much, Senator
Wicker.
Now we will call our first panel and that will be Dr.
Francis Collins. Dr. Collins is no stranger to all of us here
and certainly not to this subcommittee. Dr. Collins was sworn
in last year as the 16th Director of the NIH, a physician
geneticist noted for his discoveries of disease genes and of
course for his outstanding leadership of the Human Genome
Project. And prior to becoming the NIH Director, he served as
the Director of the National Human Genome Research Institute at
NIH.
Dr. Collins received his B.S. from the University of
Virginia, an M.D. from the University of North Carolina at
Chapel Hill, and a Ph.D. from Yale.
As I said, last August he was confirmed unanimously by the
United States Senate to be our 16th Director of the NIH.
So, Dr. Collins, welcome back. Your statement will be made
a part of the record in its entirety. I have got the clock set
at 10 minutes. Please take at least that amount of time. If you
need a few more, we will give you that too to give us your
thoughts and your views on where we are with embryonic stem
cell research and the whole area of stem cell research and what
the status is right now. Dr. Collins, welcome back.
STATEMENT OF FRANCIS S. COLLINS, M.D., Ph.D., DIRECTOR,
NATIONAL INSTITUTES OF HEALTH, DEPARTMENT
OF HEALTH AND HUMAN SERVICES
Dr. Collins. Thank you. Good morning, Chairman Harkin,
distinguished members of this subcommittee. I will make an
abbreviated version of what is in the written statement, but
thank you for the opportunity to describe some of the exciting
science that surrounds human embryonic stem cell research. And
I have some visual aids that perhaps will assist in terms of
conveying some of these points, and you should have hard copies
of those visuals in front of you.
It is truly an honor to appear before you today to discuss
this topic, and I would like to thank this subcommittee for its
steadfast support of the NIH's mission, discovering fundamental
knowledge about living systems and then applying that knowledge
to fight illness, reduce disability, and extend healthy life.
I also want to thank you for your leadership in advancing
human embryonic stem cell research. From your very first
hearing in December 1998, as the chairman has already referred
to, this subcommittee has provided a forum for discussing the
great promise of this research and has enabled NIH to invest
more than $500 million in this promising research.
But today there is a cloud hanging over this field. The
preliminary injunction issued on August 23, now stayed pending
further order from the court of appeals, has created deep
uncertainty in the field of human embryonic stem cell research.
Some of our Nation's most promising researchers such as these
stem cell scientists you see here working in the laboratories
of Drs. Morrison, Daley, and Melton are now asking should I
even bother to submit my new ideas to NIH. And young scientists
who were excited about careers in stem cell research are now
worried about going into this field given the legal
uncertainty.
But let us keep the focus of this discussion where it
belongs. The real reason for distress about the current legal
uncertainty is that patients may have to put hope on hold.
While we continue through this legal process, we must keep
patients and their families foremost in our thoughts. Patients,
after all, are at the heart of the NIH mission and are the ones
who stand to benefit the most or to lose the most by the stem
cell policies we are discussing today.
I am not a lawyer. I speak to you today as a doctor and a
scientist, and I appreciated the Chairman's exhortations that
for the witnesses at this table, myself and Dr. Daley and Dr.
Morrison, Dr. Peduzzi Nelson, and our wonderful advocate who is
herself affected by a spinal cord illness, that we should stick
to the science, and that is my goal.
But I want to take a few minutes to outline for you the
promise of human embryonic stem cell research, research that
could be, frankly, hobbled permanently unless stable Federal
funding can be assured over the long term. So let us go through
this.
There are three different types of human stem cells. All of
them are interesting. All of them are important, and it is
important to describe the properties of each.
HUMAN EMBRYONIC STEM CELLS
Let us begin with human embryonic stem cells since that is
the main topic of this morning's hearing. I will begin with a
brief overview of the remarkable properties of these cells and
then describe how they can be used to understand the molecular
basis of development and disease to regenerate and repair
tissue and to screen for new therapeutics.
Human embryonic stem cells possess several unique
characteristics. First, these cells are called pluripotent, a
word which means they have the potential to become nearly every
one of the different types of cells in the human body, as you
see here.
Second and importantly, these cells are self-renewing. That
means they are able to multiply in essentially limitless
numbers in the lab over many years and to be shared with
researchers around the world.
Now, before I go on to describe the potential applications
of human embryonic stem cell research, let me emphasize,
though, that as scientists, we are also intensely interested in
other types of stem cells. Each has different properties,
different potential applications. So let me speak for a moment
about adult stem cells.
ADULT STEM CELLS
These are found in various organs and tissues throughout
the body. These cells have been studied for more than 50 years
and have saved many lives through procedures such as bone
marrow transplantation. But because they do not divide
indefinitely and produce only a limited repertory of cell
types, they are called multipotent rather than pluripotent. And
that limitation makes them less than ideal for some types of
research.
But let me be clear and demonstrate it by the graph you see
here. NIH is strongly committed to research using adult stem
cells (in blue) because there may be other clinical
applications for which they prove useful that we do not know
about yet. So as you can see from this graph, we have been
spending considerably more on adult stem cell research (in
blue) than on human embryonic stem cell research (in red) for
the last several years.
INDUCED PLURIPOTENT STEM CELLS
Now a new and third category of stem cells are these so-
called iPS cells, which is what I will call them now. These
were created as a direct result of the knowledge gained from
studying human embryonic stem cells and understanding their
biology. This type of stem cell was only first produced in 2007
when scientists used a virus to insert molecular instructions
into the DNA of skin cells, instructions that, amazingly
enough, turned back the cells' developmental clock. These new
iPS cells possess many properties of human embryonic stem
cells. They continue to divide indefinitely and they have the
potential to give rise to nearly all the cells of the human
body. iPS cells have the added potential clinical benefit of
avoiding transplant rejection since they can be derived
directly from the patient. But let us be clear. They are not
well understood yet. There is growing evidence, including from
one of the members of the next panel, for subtle differences
between iPS cells and human embryonic stem cells. Whether this
will matter for clinical applications is not yet clear, but
virtually all investigators working in the field agree that
ongoing comparisons between iPS cells and human embryonic stem
cells are critically important because human embryonic stem
cells remain the gold standard for pluripotency. So to prohibit
work on human embryonic stem cells will, thus, do severe
collateral damage to the new and exciting research on iPS
cells.
THREE KEY USES OF HUMAN ES CELLS
Now I want to turn to the first of three key uses of human
embryonic stem cells, going back to talk specifically about
them for the rest of my comments.
Their value in understanding the molecular pathways and
development in disease is the first of these three. So, for
example, you might ask, what genes are expressed in human
embryonic stem cells and how is that programming altered as
these cells move down pathways to become blood cells, muscle
cells, or brain cells, and how does that go awry in the
presence of a disease mutation and cause an illness or a birth
defect? One of the very best windows we have now into human
development is through these human embryonic stem cells. For
example, scientists are using these cells to study diseases
such as Fragile X syndrome, which is a developmental
disability, a rather common one affecting primarily boys; Rett
syndrome, a debilitating brain disorder affecting primarily
girls; and Huntington's disease, a late-onset neurodegenerative
disease.
A second area, an exciting one and the one that has
probably generated the greatest public excitement, is
regenerative medicine, the idea that human embryonic stem cells
could actually be used as a cell therapy to replace damaged
tissues for somebody with Parkinson's disease or diabetes. We
might someday be able to regenerate damaged heart muscle tissue
in heart attack patients.
One of the most exciting and most advanced possible
therapeutic applications of human embryonic stem cells is for
patients who have been paralyzed by catastrophic spinal cord
injury. And here in this x-ray is an example of what that has
done in this patient to disrupt the spinal cord. Researchers at
the University of California-Irvine and the biotech company,
Geron, as well as at several other universities and companies
around the country, are pursuing the possibility that human
embryonic stem cells can be directed to generate spinal cord
cells for transplantation. And this summer, this being rather a
landmark year, Geron began phase I clinical trials of its
techniques for converting human embryonic stem cells into a
type of neuronal cell called an oligodendrocyte, which is a bit
of a mouthful, that is intended for injection into the
patient's spinal cord at the site where injury has occurred.
And I am going to show you a computer animation that will
show you what this looks like. So we are now going to zero in
on some neurons and their axons, which are transmitting
electrical signals, which in the spinal cord have to cross
great distances. And there, that is an oligodendrocyte that
provides the insulation that allows those signals to pass. If
the spinal cord is injured, the signals cannot go through. So
adding these human embryonic stem cells that have been turned
into oligodendrocytes should--and this has been documented in
animals--allow a repair of what is otherwise a blocked signal,
so that it can reach the limbs of the affected individual.
The potential of this approach in restoring limb function
has been repeatedly demonstrated in animal tests, some of which
are pretty dramatic. But no one is sure whether this will work
in humans with severe spinal cord injury, and even if it does,
it will take years of additional rigorous research and testing
before a standardized therapy can be developed. Yet, I think
anyone looking at this opportunity would say the potential here
is truly amazing.
HIGH-THROUGHPUT DRUG SCREENING
A third area of opportunity for human embryonic stem cells
and one that has not received as much attention--but I thought
you should know about it, because it is actually quite exciting
for scientists involved in this, is the potential to catalyze
dramatic advances in therapeutics by using these cells as a
tool to search for new drugs. Let us consider a specific
example.
We desperately need new drugs for a disease called
amyotrophic lateral sclerosis (ALS). You mentioned you have had
a witness on this very topic speaking about that, who is no
longer with us, and this is a disease which, unfortunately once
it appears, progresses rapidly. This is Lou Gehrig's disease.
It is characterized by the progressive loss of motor neurons in
the spinal cord which normally provide the connection between
the brain and the muscles of the body.
Now, ideally we would like to find a drug that stabilizes
those human motor neurons against this kind of cell death, but
how? Well, suppose you could test a library of hundreds of
thousands of candidate drug compounds, knowing that somewhere
in there, there might be one that would be valuable encouraging
motor neurons to survive. That would be a very attractive
approach to ALS. Well, can we actually do that?
I am showing you now a video of three hard-working and
uncomplaining yellow robots who are doing high-throughput drug
screening, and this is in a facility right up in Gaithersburg,
Maryland. This is done in a miniaturized format, supported by
NIH, that allows researchers to test the effect of more than
100,000 drug compounds in 48 hours and can, therefore, save
months or years of time.
This is not a pipe dream. It is a reality. Lee Rubin's lab
at Harvard is carrying out exactly this kind of experiment for
ALS right now. The possibility that human embryonic stem cell
research might one day enable us to identify a therapy for the
disease that claimed the lives of so many, including Senator
Jacob Javits, gives you some hope that this new application may
provide answers that we desperately need.
CONCLUSION
So in conclusion, Mr. Chairman, I would like to emphasize
that human embryonic stem cell research provides enormous but
mostly untapped promise for medicine, but this field has been
thrust into a precarious state. If this research is slowed or
halted, the greatest loss will be suffered by the millions of
Americans with conditions that might be helped by human
embryonic stem cells. Such people include those suffering from
heart disease, from diabetes, from liver disease, from vision
problems, along with those afflicted by spinal cord injuries
and neurodegenerative conditions like ALS and Parkinson's
disease.
The many messages I have received from patients since the
issuance of the preliminary injunction on August 23 reflect
these deep concerns. Let me just read you part of one such
message written to me by the mother of two boys who have
juvenile diabetes, and she suffers from early-onset Parkinson's
disease. Here is what she says:
``I have held my breath with hope that my sons would
benefit from the early stem cell research. I watched as
American scientists and science fell further behind on the
global scene during the past decade. In 2009, I had such hope
that once again our medical schools and universities would
begin to attract the best and brightest young minds to work in
this exciting and promising area of research.''
She finishes with this:
``This week's news was devastating to me. I had no idea how
strongly I would be affected by it. Your message of support for
the research once again gives me hope, hope that there will be
change, hope that we will see effective treatments in our
lifetimes for these devastating diseases.''
prepared statement
Hope, Senator. When someone is seriously ill or has a loved
one who is facing a life-threatening disease, it is often hope
that sustains them, provides the strength and determination to
prevail. Moving forward responsibly with all types of stem cell
research gives us and them good reason for hope, hope that is
informed by science, rigorous science. Patients and their
families are counting on the research community to find those
cures and treatments. Please help us do our part to turn that
hope into reality.
Thank you, Mr. Chairman, for your strong support of stem
cell research, and I would be happy to answer any questions.
[The statement follows:]
Prepared Statement of Francis S. Collins
Good morning, Chairman Harkin and distinguished members of the
subcommittee. It is an honor to appear before you today to discuss
human embryonic stem cell research. First, I'd like to thank this
subcommittee for its steadfast support of the National Institutes of
Health's (NIH) mission: discovering fundamental knowledge about living
systems and then applying that knowledge to fight illness, reduce
disability, and extend healthy life. NIH is grateful for the confidence
that Congress--and this subcommittee in particular--has shown in our
ability to achieve this mission, as evidenced by our current $31
billion budget, and the $10.4 billion provided to NIH through the
American Recovery and Reinvestment Act. Your support makes our mission
possible, and we are very grateful.
Nowhere has this support been more evident than in this
subcommittee's leadership in advancing human embryonic stem cell
research. From your first hearing in December 1998, this subcommittee
has provided a forum for discussing the great promise this research
holds. With your steadfast support, NIH has invested more than $500
million in human embryonic stem cell research; one of the most
promising research avenues of recent times.
The preliminary injunction issued on August 23 by U.S. District
Court Judge Royce Lamberth in the Sherley v. Sebelius case, now stayed
pending further order from the Court of Appeals, has created
uncertainty in the field of human embryonic stem cell research. Many
researchers across the country have considered modifying their research
plans to turn away from an area of research that, while promising, is
now fraught with uncertainty. Some of our Nation's best researchers,
who have written grant applications proposing innovative new ideas, are
now asking, ``Should I even bother to submit my proposal to NIH?''
Likewise, young scientists excited about careers in stem cell research
are concerned about going into this field, given the legal uncertainty.
But the real reason for distress about the current legal
uncertainty is that patients may have to put hope on hold. While we
continue through the legal process, I hope that we can keep the
patients and their families in our thoughts. They are at the heart of
the NIH mission, and they are the ones who stand to benefit the most,
or lose the most, by the stem cell policies we are discussing today.
I am not a lawyer, and I speak to you today as a doctor and a
scientist. In that capacity, I want to outline for you the promise of
human embryonic stem cell research--research that could be hobbled
permanently unless stable Federal funding can be assured over the long
term.
I want to begin with a brief overview of the remarkable properties
of human embryonic stem cells and then describe how research using
these cells will:
--provide key insights into the molecular pathways in development and
disease;
--allow for the development of tissue replacement or regenerative
medicine; and
--enable more targeted and efficient screening of new drug
candidates.
Human Embryonic Stem Cells
Human embryonic stem cells possess several unique characteristics.
First, these cells are pluripotent, which means that they have the
potential to become nearly every one of the different types of cells in
the human body. Second, these cells are self-renewing, which means that
they are able to multiply in essentially limitless numbers in the lab
over many years and to be shared with many researchers around the
world.
To be sure, scientists are also interested in other types of stem
cells. Adult stem cells are found in various organs and tissues
throughout the body. These cells, also sometimes referred to as
multipotent or somatic stem cells, can develop into a limited number of
specific cell types, depending upon the organ or tissue from which they
are derived. However, adult stem cells are less than ideal for many
types of research and therapy because they do not divide indefinitely
in culture, and they produce only a limited number of cells and cell
types.
In considering the relative benefits of adult and embryonic stem
cell research, keep in mind that research on the most abundantly
available source of adult stem cells, hematopoetic stem cells in bone
marrow, began more than a half-century ago. In fact, Drs. E. Donnall
Thomas and Joseph Murray were awarded the Nobel Prize in Medicine in
1990, ``for their discoveries concerning organ and cell transplantation
in the treatment of human disease.'' Indeed, this research has produced
clinically validated and widely used treatments that reconstitute the
immune system after leukemia, lymphoma, and various blood or autoimmune
disorders have been treated with chemotherapy.
NIH is strongly committed to research using adult stem cells
because there may be other clinical applications for which they prove
useful. NIH has invested many hundreds of millions of dollars over the
years in adult stem cell research. Indeed, annually we are spending
almost three times as much on adult stem cell research as on human
embryonic stem cell research.
A new and third category of stem cells are induced pluripotent stem
(iPS) cells, which were created as a direct result of the knowledge
gained from studying human embryonic stem cells. This type of stem cell
was first produced in 2007, when scientists discovered that it is
possible to instruct adult skin cells to return to a very early
developmental stage. They accomplished this by using viruses to insert
molecular instructions into the DNA of skin cells--instructions that
acted to turn back the cells' developmental clock. These new cells
possess many properties of human embryonic stem cells: they continue to
divide indefinitely and are pluripotent, with the potential to give
rise to all the cells of the human body.
While induced pluripotent stem cells are of great interest to
scientists, and have the added potential clinical benefit of avoiding
transplant rejection since they can be derived directly from the
patient, they are not well understood yet. A growing body of research,
including a publication just 2 months ago from Dr. George Daley, who is
here today, and his collaborators suggests that there are subtle, but
potentially important differences between iPS cells and human embryonic
stem cells. On close examination with powerful molecular
fingerprinting, it seems that iPS cells retain some memory of the
tissue from which they were derived. Whether this will matter for
clinical applications is not clear, but virtually all investigators
working in the field agree that additional comparisons between iPS
cells and human embryonic stem cells are critically important. Human
embryonic stem cells remain the gold standard for pluripotency: to
prohibit work on human embryonic stem cells will thus do severe
collateral damage to the new and exciting research on iPS cells.
Molecular Pathways in Biological Development and Human Disease
While many researchers are focused on coaxing human embryonic stem
cells to develop into a particular cell type, such as insulin-secreting
cells or liver cells, understanding the basic biology of stem cells
themselves will be extremely valuable to understanding human
development. We have learned much about the genes required for
pluripotency, but there is much more to understand. For example, what
genes are expressed in human embryonic stem cells? How is that program
altered as these cells move down pathways to become blood cells, muscle
cells, or brain cells? How are these steps regulated? What happens if
one of the genes doesn't function properly? Our best window into human
development is using human embryonic stem cells.
In addition to understanding normal human development more
completely, human embryonic stem cells are providing key tools to help
us study the origins of many devastating diseases that afflict babies
and young children. Such research may even help to uncover targets for
drug development. We now have a number of human embryonic stem cell
lines that are known to carry mutations that cause specific diseases.
For example, scientists are studying cell lines with a mutation in the
FMR1 gene that causes Fragile X, a developmental disability. The FMR1
gene normally makes a protein that the brain needs to develop properly.
However, the Fragile X mutation in the FMR1 gene causes the body to
make only a little or none of the protein. Research using human
embryonic stem cells with this mutation showed that although the FMR1
gene is expressed normally in Fragile X, it is turned off after the
cells begin to differentiate. How this happens is something we can
study using human embryonic stem cell lines. Dr. Daley also studies a
number of human embryonic stem cell lines with various genetic
mutations, and I am sure he can tell you more about his research.
One ongoing NIH grant focuses on Rett syndrome, a debilitating,
developmental brain disorder generally afflicting young females and
caused by mutations in a gene called MECP2. This research uses human
embryonic stem cells to generate human brain cells with a deficiency in
the MECP2 gene, and then studies the effects of this deficiency on the
development and functions of these brain cells. Such research could
improve our understanding of Rett syndrome, and facilitate the
development of therapies for it.
Another research team has recently generated human embryonic stem
cell lines containing mutations in the HTT gene that causes
Huntington's disease, a late-onset neurodegenerative disease.
Huntington's disease has been studied for a long time, but the normal
function and pathogenesis of the protein coded for by the HTT gene is
not fully understood.
Tissue Replacement or Regenerative Medicine
One of the more exciting and high-profile potential applications of
human embryonic stem cell research is the possibility that such cells
can be programmed to replace or regenerate tissues damaged by disease
or injury. For example, we might one day be able to regenerate damaged
heart muscle tissue in heart attack patients, develop insulin-producing
pancreatic beta cells to replace those lost or damaged in people with
Type 1 diabetes, or restore spinal cord neural connections in patients
paralyzed by catastrophic spinal cord injury.
Part of the devastation that heart attack victims suffer is that,
because of restricted blood flow and oxygen deprivation, their heart
muscle cells die, leaving the heart much weaker and less able to pump
blood throughout the body. Today we are studying the tantalizing
possibility that human embryonic stem cells, or perhaps adult stem
cells or iPS cells, might be programmed to replace damaged or destroyed
heart muscle cells, known as myocardial cells. The prevalence of heart
disease, along with the scarcity of hearts and heart tissues available
for transplantation and the associated clinical and autoimmune problems
of transplantation, make this line of research imperative.
Type 1 diabetes is a disease in which a specific type of cell,
insulin-producing pancreatic beta cells, is damaged or destroyed by the
patient's own immune system. A major challenge is to understand the
autoimmune response that kills these cells in children who then develop
Type 1 diabetes, but human embryonic stem cells offer the hope that we
might one day produce replacement cells that avoid the autoimmune
challenges associated with today's rudimentary transplantation
therapies. To do that, we need to know more about how stem cells are
genetically programmed, how they differentiate, and how they renew
themselves; but as our understanding and ability to work with these
cells expands, we are laying the foundation for an entirely new--and
much more effective--way to address the devastation of Type 1 diabetes.
One of the most exciting--and most advanced--possible therapeutic
applications of human embryonic stem cells is for patients who have
been paralyzed by catastrophic spinal cord damage. Researchers at the
University of California--Irvine and at the biotech company Geron
Corp., as well as at other universities and companies around the
country, are pursuing the possibility that human embryonic stem cells
can be directed to generate spinal cord cells for transplantation.
This summer, Geron began phase I safety trials of its technique for
converting stem cells into a type of neuronal cell, known as
oligodendrocytes, intended for injection into the patient's spinal cord
at the site where it has been severed by injury. The hope, which has
been repeatedly demonstrated in animal tests, is that the newly
injected oligodendrocytes might repair the damaged insulation around
the severed nerve cells of the spinal cord, and thereby enable those
cells to once again send signals to the patient's limbs and organs. We
are not sure that this approach will work, and even if it does, it will
take years of additional research and testing before we can develop a
standardized therapy using these techniques. Still, the potential that
this research holds is truly amazing.
For all of these efforts, there are many scientific challenges that
must be addressed. We need to figure out how to get human embryonic
stem cells to differentiate down specific pathways in a well-controlled
process. We also need to make sure that the resulting cells behave in
predictable ways. Because human embryonic stem cells are immortal and
can proliferate endlessly--much like cancer cells--we need to be sure
that they or their differentiated ``daughter'' cells do not produce
tumors or otherwise harm patients. The field of regenerative medicine
is young. It is unreasonable for us to think we will have cures within
a set time period. It is also wrong to overpromise on the speed and
scope of such research to patients and their families. But we must
persevere and move this research forward in a strong and consistent
manner. That is why the delay and uncertainty associated with the
current legal situation is so disheartening for both researchers and
patients. As I said at the time the injunction was issued, this
unexpected development is like pouring sand into the engine of
discovery.
Targeted, Efficient Screening of New Drug Candidates
Recently, human embryonic stem cells have received increasing
attention as a tool for drug screening. High throughput drug screening
is done in a miniaturized format that allows researchers to test the
effect of more than 100,000 chemicals on a gene, protein, cell, or
organism of interest. It is a highly automated process that can test in
one day what would otherwise take a researcher months or years. Because
human embryonic stem cells can differentiate into specific human cell
types in large quantities, they provide the foundation for high
throughput screening of candidate drug compounds for a given disease.
This means that we now have the capacity to identify efficiently drugs
that work in a targeted cell type.
This is not a promise, it is reality. Human embryonic stem cells
are currently being used to identify drug candidates that can slow or
stop the progression of amyotrophic lateral sclerosis (ALS). Also
called Lou Gehrig's disease, ALS is an ultimately fatal disease
characterized by the progressive loss of motor neurons, which provide
the connection between the brain and the muscles of our body. The
possibility that human embryonic stem cell research might one day
enable us to identify a therapy for the disease that afflicts
astrophysicist Stephen Hawking and claimed the life of Senator Jacob
Javits, gives you some sense of the hope this new application might
provide.
There are very few drugs available for ALS, and none that prolong
the patient's life for more than a few months. Dr. Lee Rubin, a
researcher at Harvard's Stem Cell Institute, and his colleagues have
developed an elegant set of studies to screen for drugs that prevent
motor neuron death. The scientists differentiated mouse embryonic stem
cells into large numbers of motor neurons and exposed them to thousands
of compounds to find the ones that improve the survival of these vital
cells. Dr. Rubin and his team identified a handful of promising
compounds that they then tested in motor neurons derived from human
embryonic stem cells. The most promising of these can now be moved
further along the pipeline from drug discovery to clinical trials.
Drugs fail for many reasons: lack of efficacy in humans is
responsible for 30 percent of drug failures, and unpredicted toxicity
is responsible for more than 20 percent of failures. The traditional
methods of using animal or abnormal human cell lines for safety and
efficacy testing provide a poor model of how a human will respond to a
particular drug. Human embryonic stem cells can generate the
appropriate cell type and even disease cell lines for efficacy testing
early on, as in the case of the ALS study. They are also being used to
understand the toxicity of promising compounds in the early stages of
drug development. For example, liver toxicity is a common cause of drug
failure. Human embryonic stem cells can be differentiated into human
liver cells, or hepatocytes, which are then exposed to novel drugs to
identify any obvious liver toxicity and provide early insight on how a
drug will be metabolized by the liver. In this manner, human embryonic
stem cells provide drug developers and researchers a model of how
actual human livers will respond to a drug. Our hope is this will
reduce the number of drugs that fail in human clinical trials because
of low efficacy or unacceptable toxicity.
The NIH Stem Cell Guidelines
President George W. Bush first funded research on human embryonic
stem cells--but that decision only allowed the use of cell lines that
had been derived before August 9, 2001. Ultimately, that only amounted
to 21 cell lines, and as science moved forward it was clear that this
somewhat arbitrary time stamp was significantly inhibiting the field.
On March 9, 2009, President Barack Obama issued Executive Order 13505,
Removing Barriers to Responsible Scientific Research Involving Human
Stem Cells. The Executive Order states that the Secretary of Health and
Human Services, through the Director of NIH, may support and conduct
responsible, scientifically worthy human stem cell research, including
human embryonic stem cell research. This Executive Order prompted a
rapid expansion of scientific effort and progress.
The President asked NIH to review existing human stem cell research
guidelines and issue new guidelines, consistent with the President's
Executive order, within 120 days. NIH immediately began a comprehensive
review that resulted in draft guidelines that were published in the
Federal Register for public comment on April 23, 2009. After careful
analysis of more than 49,000 comments from scientific, patient
advocacy, medical, and religious organizations, as well as private
citizens and members of Congress, NIH published final guidelines,
effective July 7, 2009. The guidelines provide a framework for funding
scientifically worthy research using responsibly derived human
embryonic stem cells. The guidelines restrict Federal funding to cell
lines derived from embryos that: were created for reproductive purposes
and were no longer needed for that purpose; were donated for research
by individuals who sought reproductive treatment; and for which the
donors gave voluntary written consent. Since the President issued his
Executive order and NIH implemented its guidelines, 75 human embryonic
stem cell lines have been approved for use in NIH-funded research. All
were reviewed rigorously and found to meet the high ethical standards
laid out in the NIH guidelines. The review process is so rigorous that
48 stem cell lines have not been approved for use in federally funded
research. Prior to the court's order, in fiscal year 2010, NIH funded
199 grants for research on human embryonic stem cells totaling $137
million. These grants support a broad range of research including
studies to improve stem cell technologies, studies to compare different
types of stem cells, and studies to develop cell types for use in
treating debilitating diseases and disorders such as diabetes, liver
failure, and neurodegenerative diseases.
If the Government is not successful in defending the guidelines in
this litigation, and NIH will have to withdraw future NIH support for
all grants involving human embryonic stem cell research, drastic
scientific consequences will occur. Since funding for these projects
would be discontinued mid-stream, all the funds that have been put in
accounts or already drawn down--$270 million over the 2- to 5-year life
of these grants, including what has been provided fiscal year 2010--
would have been wasted. The research momentum that this subcommittee
worked so hard to achieve would be lost.
Young scientists may opt out of this field due to the chaos of
stopping, then starting and now stopping again. More senior
investigators may look to other countries, such as Singapore, China,
and the United Kingdom to pursue their work. The greatest loss,
however, will be for the millions of Americans with conditions
currently under study with human embryonic stem cells. Such people
include those suffering from heart disease, diabetes, liver disease,
and vision problems, along with those afflicted by spinal cord injuries
and neurodegenerative conditions like ALS and Alzheimer's disease. The
many messages I have received from patients since the issuance of the
preliminary injunction reflect these deep concerns. Here is part of
just one such message:
``I am a mother of two adult sons with Type I diabetes (since age
7), and a person with young onset Parkinson's disease. I have watched
as my oldest son moved from taking the old beef/pork insulin to taking
genetically engineered insulin, and have held my breath with hope that
my sons would benefit from the early stem cell research.
``I watched as American scientists and science fell farther behind
on the global scene during the past decade. In 2009, I had such hope
that once again our medical schools and universities would begin to
attract the best and brightest young minds to work in this exciting and
promising area of research.
``This week's news was devastating to me. I had no idea how
strongly I would be affected by it. Your message of support for the
research once again gives me hope. Hope that there will be change. Hope
that we will see effective treatments in our lifetimes for these
devastating diseases.''
Thank you, Mr. Chairman, for your strong support of stem cell
research. I would be happy to answer any questions.
THE NEED FOR ADDITIONAL STEM CELL LINES
Senator Harkin. So, Dr. Collins, thank you. As usual, a
very lucid and understandable presentation of a very complex
issue and complex science.
We will begin a round of 5-minute questioning. We have two
votes, I think, starting at 10:45 a.m., if I am not mistaken.
So we will do as much as we can, and then we will return.
Because of the Executive order signed, the number of stem
cell lines eligible for Federal funding rose from 21 to 75. Dr.
Collins, why is this important to scientists? What can
researchers do with these additional lines they could not do
before? Would it help to have even more lines?
Dr. Collins. I think President Bush deserves credit for
being the first to provide Federal funds for human embryonic
stem cell research, and that did lead to these 21 lines that
have been utilized over the course of several years. But they
were derived a long time ago and many of them under
circumstances that today we would say are less than ideal.
There are many advances in the science over that time table,
and many other stem cell lines being derived during that time
table since 2001 were not available to scientists who had great
interest in studying them.
In particular, to be able to have available human embryonic
stem cell lines that have specific genetic mutations in them
would be a great advance in terms of the ability to study
certain diseases such as Fragile X, for instance, or
Huntington's disease, and such were not in the collection of 21
lines.
Furthermore, those 21 lines were very nondiverse in terms
of their origins, nearly all of them coming from individuals of
Northern European background, and if you were seriously
thinking about the possibility of utilizing these
therapeutically, as Geron is now doing for spinal cord injury,
that could greatly limit the ability to use them for people of
different backgrounds. So there is enormous enthusiasm and
intense interest on the part of the scientific community to
have this panel broadened, and the Obama Executive Order of
March 2009 made that possible under carefully described
conditions to maintain the most ethical standards in terms of
how such lines would have to have been derived in order to
qualify for Federal funding. And NIH now has on its registry 75
lines that have met those standards and more to come.
LIMITATIONS OF ADULT STEM CELLS
Senator Harkin. Very good.
In Senator Wicker's opening statement, he said the
following:
``People suffering from dozens of diseases and conditions,
including cancer, juvenile diabetes, Parkinson's, MS, leukemia,
lymphoma, spinal cord injuries, and corneal regeneration, among
many others, are turning to adult and induced pluripotent stem
cell treatments for help.''
My understanding has been that while adult stem cells are
used routinely to treat blood diseases, this is not the case
for any other type of disease. Could you please enlighten us on
that aspect?
Dr. Collins. Sure. Adult stem cell research has been
studied now for more than 50 years----
Senator Harkin. You said that.
Dr. Collins [continuing]. And certainly has been primarily
utilized clinically for bone marrow transplantation where it
has been of great value. We are, as you saw from the graph,
spending almost $400 million a year on non-embryonic stem cell
research, looking for additional applications where adult stem
cells could also be of benefit. And the Senator's opening
statement mentioned some areas of potential interest, but they
are far from being what you would call standardized care yet.
They are experimental.
I think one of the unfortunate aspects of the discussion
about human embryonic stem cells is that it has somehow implied
that scientists are opposed to research on adult stem cells.
Not at all. Speaking for myself and the others who will be here
today, we celebrate all of the ways that every kind of stem
cell can be utilized for effective research, but should we not
be pursuing the most exciting options in parallel and not
assuming that we know one of them is going to be better than
the other? Because right now, we have absolutely no reasons to
say that. And I think most would assume that, depending on the
application, adult stem cells may be better in one instance;
embryonic stem cells may be better in another. We will never
know if we are not allowed to do the research.
Senator Harkin. So it is not just two different camps. It
is a blending of all of this.
Dr. Collins. Absolutely. Dr. Daley would probably tell you
he has made major advances in both those fields, and he would
be right.
IMPORTANCE OF FEDERAL FUNDING
Senator Harkin. Lastly, we sometimes hear opponents of this
research say Federal funding is not needed. There are other
potential sources of money in the private sector. How would you
respond to that?
Dr. Collins. Well, of course, that was an argument that
basically prevailed before there was any allowance for Federal
funding for human embryonic stem cells and led to some States
taking action. But most of the really critical observations
that need to be made in terms of understanding the potential of
human embryonic stem cells are unlikely to happen without the
kind of Federal support in our best universities and medical
centers around the country. That is where the talent often lies
for doing those really fundamental explorations of the nature
of these cells. To assume that private sector investment,
although it is critical in terms of those ultimate
translational steps, is going to be sufficient is to not
understand the many steps that we need to pursue now in order
to fully flesh out the potential of this approach to treating a
long list of conditions.
Senator Harkin. Thank you very much, Dr. Collins. My time
is out. I do have a couple of follow-up questions, but I will
wait my turn. I will turn to Senator Cochran for his.
Senator Cochran. Dr. Collins, we were talking specifically
today about the options for Federal support for research and
specifically using embryonic stem cell therapy. What in your
judgment would happen if we did not approve Federal funding or,
if for some reason, the funding sources in the Federal
Government to support this kind of research dried up for
whatever reason--action of Congress or, heaven forbid, running
out of money?
Dr. Collins. If Federal funds were terminated for the
support of human embryonic stem cell research, that would be an
absolutely devastating outcome. You would see large numbers of
scientists who have already developed a lot of momentum in this
field becoming extremely disillusioned. You would see many of
them potentially moving into other research areas or moving
overseas. Most importantly, you would see that hope for the
treatment of many diseases that we currently lack effective
ways to intervene being dashed.
I do not want to overstate here the potential for human
embryonic stem cell research to solve all those problems
because we just do not know, and we have to be careful that our
hope does not turn into hype, and I think people here will be
careful about that. But you know, if you were living in 1950
and somebody said, you know, those iron lungs are working
pretty well, maybe we do not need to do anything more about
polio, what a terrible mistake that would have been. So we have
some science now that is working in some areas, but we have
this new potential to do something really that is game-
changing. To have that cut off at the knees would be a
devastating blow.
And let me say one other thing that I tried to put into my
statement which I think has not been appreciated. It is not
sufficient to say, well, we now have iPS cells, so we do not
need human embryonic stem cells anymore. We have to compare
those side by side, every step of the way right now, because we
do not understand the subtle differences between them and what
that might mean, and if we give up doing that comparison to the
gold standard for pluripotency, we may damage the potential of
iPS cells just as they are beginning to gather momentum.
Senator Cochran. Well, I appreciate very much your being
here today. I think your testimony has helped us understand in
a real way, a practical way, what the consequences are for a
breakdown in Federal support for this research. Thank you very
much.
Dr. Collins. Thank you, Senator.
Senator Harkin. Senator Specter.
Senator Specter. Thank you, Mr. Chairman. I thank you for
your generous comments and for scheduling this early hearing to
take up the important subject of embryonic stem cell research.
I look forward to debating with Senator Wicker the issues which
he has raised more appropriately on the Senate floor than in
this hearing, I think, and would ask unanimous consent that a
commentary by Bob Schieffer on 60 Minutes be included in the
record where there is a comparison between those who oppose
stem cell research with those who challenged the use of
Galileo's telescope because they believed their doctrines and
tradition had already told them what was necessary to be seen.
[The information follows:]
[From www.cbsnews.com, August 29, 2010]
Stem Cell Injunction Dictated by Doctrine
(By Bob Schieffer)
Last week two people I know were diagnosed with colon cancer, one
of the deadliest of all cancers.
Because my wife and I are cancer survivors, and because my mother
died of cancer because she was afraid to go to the doctor, I've come to
know a little about the disease.
My friends have a serious illness, but there is a path to recovery
that was not there not so long ago. And as I talked to them last week,
I was again struck by the remarkable progress science is making to give
them that path.
Being told we have cancer no longer means we've been given the
death penalty.
Like all scientific breakthroughs, advances in cancer research
began and depend on basic research--science's ability to go not where
doctrine or tradition dictates, but where research takes it.
Ironically, my friends were diagnosed about the time a Federal
judge issued the injunction placing limits on stem cell research, an
area that holds the greatest possibilities for medical breakthroughs
since penicillin.
I have the greatest respect for those who disagree, but to me
putting restraints on stem cell research is not far from those who
refused to look through Galileo's telescope because they believed their
doctrines and tradition had already told them what they would see.
Their beliefs, too, were deeply held--but where would the store of
knowledge be had their view prevailed?
As we again try to untangle the arguments over stem cells, let us
also consider this: No civilization, no society, has survived if its
people came to believe they knew enough and needed to know nothing
more.
IMPACT OF JUDICIAL DECISIONS
Senator Specter. The decision by the district court in the
District of Columbia has had a very serious impact on the
research. May the record show a nod by Dr. Collins. And I will
ask him specifically about that. But in our informal
discussion, he said that while they have been able to proceed
with the expenditure of Federal funds with the circuit stay,
that the researchers are very, very concerned about their
ability to move forward. And we have a stay which has been
issued until next Monday, September 20, and we do not know what
will happen after that.
That is why I moved very promptly, as soon as we were in
session--on Monday of this week we went into session at 2:30
p.m., and before 3 o'clock I had to go to the floor to
introduce legislation to overturn the court decision because
Congress has the authority to make this determination. It is
not constitutional issue. It is a matter of statutory
interpretation. And the evidence is overwhelming about the
importance of embryonic stem cell research to deal with the
maladies of the world. And if there are 400,000 frozen, which
will be lost and that we are not dealing with human life--if
they would be turned into human life, no one would suggest
using them for medical research.
The vicissitudes of the legal battle are very, very
uncertain as to what will happen in the circuit court, whether
the stay will be maintained or whether the Supreme Court might
issue a stay. There have been surprising stays issued by the
Supreme Court in the past several months. There was an Arizona
campaign finance law which provided for public funding where
the Court of Appeals for the Ninth Circuit upheld the law,
overruling the district court, and the Supreme Court of the
United States, without even a petition for certiorari filed,
intervened in the case to grant a stay--really unheard of--on
ideological grounds.
We had a trial in process before Chief Judge Walker in San
Francisco on the issue of gay marriage, and the Supreme Court
intervened to stop televising on closed circuit television.
So the legislature, the Congress, had better get busy and
it better act on this subject so we do not await court action.
We do not put the scientists under the pressure of knowing what
may or may not happen.
I have a couple of questions for you, Dr. Collins. The
first question relates to the impact of the judicial decision,
and I have gotten the information that more than $500 million
has been expended on embryonic stem cell research. Well,
actually three questions.
Question number one is what has the impact been on the
scientists now using NIH funding for embryonic stem cell
research in terms of the uncertainty of the future.
Number two, what results have been taken in a positive
sense, which I know are very good for the more than $500
million already expended?
And what has been the consequence of the $10 billion in the
stimulus package where you informally told me that it has
created a tremendous excitement and a new wave of enthusiasm by
researchers who had been discouraged by the failure of Congress
to keep the pace, which we had moved from $12 billion to $30
billion, but failure to keep the pace in funding since 2003?
THE EFFECT OF THE PRELIMINARY INJUNCTION ON NIH EMBRYONIC STEM CELL
RESEARCH
Dr. Collins. Well, Senator, thank you for the question, and
let me first say how appreciative I am personally and everyone
at NIH is for the strong leadership you have shown over these
years and your advocacy for the value of medical response and
especially, because we are talking about it today, for stem
cell research. That has been much appreciated and your
articulation of the importance has always been right on target,
as it just was here in your opening statement. And we are all
grateful, indeed, for the way that you have shown that
leadership. And you, together with our chairman, have played
such a significant role in NIH being at this exciting place
that we are right now in terms of medical research
opportunities that, frankly, I did not dream we would be at 10
years ago.
But we also are here with this cloud over the enterprise in
this very specific area of human embryonic stem cell research.
When the judge issued that preliminary injunction, we were
stunned, and basically after interpretations by the Department
of Justice, took steps that we felt we had to with intramural
researchers who were working with Federal funds at that very
time doing embryonic stem cell research. We had to ask them to
stop. With extramural grantees, if they had already received a
grant and were spending down the dollars that they had already
been allocated, they could continue, but they would need to
come back for a renewal on an annual basis, and we basically
said within a year, there will be no more funds because those
annual renewals cannot be adhered to. And frankly, we had a
bunch of new grants and renewals right in front of us, about
244 grants, adding up to about $200 million, that were
immediately put on hold, not to mention a whole other set of
grants that were ready for peer review that we had to stick on
the shelf because we felt the judge's order prevented us from
acting on them.
Fortunately and to our great relief, although temporary
relief it apparently is, the stay on that particular injunction
last week allowed us to catch up and to go back to doing what
we had been doing, and we are working vigorously to be sure
that we are doing the right thing here in terms of supporting
the research that we had always intended to.
But there is this cloud of uncertainty that hangs over the
situation because there is not a clear path forward. And I
think as you will hear from others at this hearing, that is
creating great anxiety particularly amongst young scientists
who are wondering, ``Do I have a career path here or is this
something I better just not get involved in because it is too
uncertain?''
So the impact so far has been quite significant and is
uncertain going forward. We are, as I tried to show in the
graph in the opening statement, spending in the neighborhood of
$188 million--sorry--$138 million on nonembryonic--I am sorry--
on embryonic and other types of nonadult--let me try that
again. We are spending $138 million on human embryonic stem
cell research and all of that was put into jeopardy. And that
is an estimate for fiscal year 2010.
AMERICAN RECOVERY AND REINVESTMENT ACT (ARRA) AT NIH
In terms of your question about the ARRA dollars that have
flowed to NIH, that has been an enormous infusion of energy and
capability and excitement in a community that had, frankly,
been struggling after 5 years of flat budgets and many
innovative ideas lacking support. The infusion of that money
has made it possible to put into place a whole host of
innovative projects.
One of the things I have done in my first year as NIH
Director is to read a lot of those grants that came in because
of ARRA to see what was there. And it is some of the most
exciting science that you can imagine, and we have used it
specifically to encourage people to put forward out-of-the-box
ideas that might otherwise have not seemed worth trying in a
very tough budget climate. This has supported breakthroughs in
cancer, in heart disease, in diabetes, in autism, things that
really have changed the whole landscape because of this
opportunity to empower the community in ways that they had not
been previously been able to do. And I want to thank you for
your remarkable leadership in making that possible.
Of course, we have another anxiety there, that the 2 years
of ARRA are coming to a close, and the momentum that was
started is now somewhat in question.
Senator Specter. You testified about the advances
generally, but specifically on stem cells with the $500 million
expended, tell about the big results there.
Senator Murray. Mr. Chairman, before Dr. Collins answers
that, a vote has been called and I want to go to the floor. So
I just want to say really quickly----
Senator Harkin. Yes.
Senator Murray [continuing]. That, Dr. Collins, your
testimony is extremely compelling and understandable, and I
really appreciate it. I think it clarified a lot for me.
I want to thank Senator Harkin for his leadership on this,
but I especially want to thank Senator Specter too whose voice
we will miss on this panel. And we will continue to carry your
spirit forward on this critical issue. I just wanted to say
thank you very much.
We do have a vote and I want to make sure we get to the
rest of the panel.
ADVANCES IN EMBRYONIC STEM CELL RESEARCH
Senator Specter. Thank you, Senator Murray.
Well, just focus for a moment, if you would, on the $500
million already expended on embryonic stem cell research and
what tremendous advances have been made there.
Dr. Collins. So that is a long list. It has given us the
opportunity at the basic level to begin to understand what it
is that takes this cell with all of this potential and triggers
it to become a neuron or a muscle cell or a pancreatic beta
cell that makes insulin. Those signals, those elaborate
pathways of development, are now being sorted out by
researchers working on that with very powerful technologies,
some of them coming from the genome project.
And in terms of specific applications, you have heard of
the application to spinal cord injury which is now in its Phase
I clinical trial. That is the first one which has actually made
it through that. That was a lot of Food and Drug Administration
(FDA) review, believe me. But there are also applications which
are looking very promising for eye diseases and for Type 1
diabetes where human embryonic stem cells have been
differentiated into the cells needed in that circumstance and
have then been used in an animal model to show clear benefit
and rigorous science, setting the stage then for human clinical
trials in the not-too-distant future.
On top of all that, human embryonic stem cells are being
used, as I mentioned, to do drug screening because if you are
looking for a drug that might help somebody with a muscle
disease, you would really like to test and see does that work
in human muscle cells? Well, we now have the ability to make
human muscle cells because you can take human embryonic stem
cells and tweak them to do that and then test hundreds of
thousands of compounds to see what is there that would
stabilize a muscle cell, make it healthy or make it better able
to survive. A huge opportunity in drug screening which is
happening both in the private sector and in academia. All of
those things add up to that roughly $500 million and some, but
we think we are just scratching the surface of the potential
here.
Senator Specter. Thank you, Dr. Collins. That is powerful.
Senator Harkin. Thank you, Senator Specter.
Dr. Collins and others, we have a vote. There are two
votes. So we have about 6 or 7 minutes left in this vote. So I
will recess the panel. We will go vote on one, and then we will
vote on the next one. So it will be probably 15 minutes before
we get back here. So I would like to say if anybody needs to
use the facilities or something, we will be back in 15 minutes.
What I would like to ask, Dr. Collins--I hate to impose on
you, but there are a lot of things we need to cover. I would
like to ask if you could stay during our second panel. I would
appreciate that very much if you could. I am not going to put
the guards at the door, but I would really like to have you
stay.
While we are gone, I am going to ask the staff to go ahead
and put the other nameplates of the second panel up there.
But I do have some follow-up questions for you, Dr.
Collins, when we come back.
Dr. Collins. No guards needed. I am happy to stay.
Senator Harkin. All right, thanks, Dr. Collins.
We will be right back.
EMBRYONIC STEM CELLS AS A RESEARCH TOOL
Senator Harkin. The subcommittee will resume its sitting. I
thank everyone for their indulgence.
Dr. Collins, just two other things I wanted to cover with
you. One, in your testimony--and you mentioned it also in the
slides--was the power of embryonic stem cells as a research
tool. It sounds like even if these cells never actually end up
being used as therapies in which they are transplanted into
human beings, they could still teach us valuable information
that could lead to treatments and cures. I just want to ask is
that correct and just a slight elaboration on that.
Dr. Collins. That is correct, and in two ways.
One is that human embryonic stem cells, because they
represent that most pluripotent, most undifferentiated cell
type, but can be encouraged to go down various pathways to
become muscle cells or brain cells or blood cells, they give us
a window into how that development happens in humans in a way
that we did not have before. And again, if you are able to
understand what those signals are, you can also infer what goes
wrong if one of those signals misfires, and many birth defects
and many genetic diseases are in that category.
The second way, which I also mentioned, is the ability to
use these cells particularly if you turn them into neurons or
muscle cells, or whatever it is that you need to study most to
screen for new drug therapies. The way we got drugs in the past
involved a variety of approaches, trying to identify a small
molecule, an organic compound that would have the right
properties to do something you want it to, but you have often
had to try that in an animal model. These are human cells and
they are human cells that you can convince to behave pretty
much the way they would in a person except they are there in
your dish, so you can do this without the risks of toxicity. A
very powerful new way to find the next generation of drugs.
THE ETHICS OF HUMAN EMBRYONIC STEM CELL RESEARCH
Senator Harkin. Very good.
Dr. Collins, on a kind of a more personal note, opponents
of human embryonic stem cell research sometimes argue that it
is immoral. They have raised it into a moral issue. Quite
frankly, I have a number of friends, but I have one very close
family friend who had a lot of trouble conceiving a child. She
and her husband tried many different things. They finally went
to a fertility clinic, and through in vitro fertilization, she
was able to conceive and have a wonderful child. Actually twins
who are very healthy. And so that is a real blessing that
science was able to help them.
Now, I do not know this for a fact, but in many of these
cases, a lot of the embryos are left over from a process of in
vitro fertilization. And at some point, the donors are asked
what they want to do with them. And obviously, they are not
going to keep them in liquid nitrogen forever, and so they are
discarded. Some time ago, my friend said to me, well, but I
understand they could be used for embryonic stem cell research
that might help someone who is suffering. And I said, well,
yes, that is true. She said, well, I would much rather do that.
So it seems to me there is some morality there that we have
not thought about, and as you know, under the guidelines that
were issued only stem cells derived from leftover in vitro
fertilization could be used with full consent of the donors and
with no monetary consideration and could not be transplanted
into a uterus. It had to only be used for stem cell derivation.
So those are the ethical guidelines. Well, I just thought I
would lay that out. A lot of people do not understand that.
But you are well known not only as one of the world's
foremost scientists, but as a man of faith. I actually did read
your book. I thought it was very good, The Language of God. I
think it is just one of the wonderful crossover books between
science and faith. It is just a wonderful book.
Can you talk about why you personally as a pre-eminent
scientist are comfortable with this research? How do you
reconcile your advocacy for embryonic stem cell research with
your own faith and your own moral judgment?
Dr. Collins. Thank you, Senator. I think you have already
articulated the issues extremely well.
I do believe that the human embryo deserves moral respect.
It is a potential human being. This coming together of sperm
and egg is the way we all got started, and that is not
something to be taken lightly. But when you look at the
circumstances that you have just outlined in terms of the
consequences of in vitro fertilization efforts, benevolent as
they are, giving couples a chance to have children who
otherwise could not, one of those consequences is the existence
of hundreds of thousands of frozen embryos that are being
discarded potentially all the time.
And then faced with the ethical choice in that situation, I
have come to the conclusion as a person of faith that the
alternative of discarding this embryo that is clearly not going
to get used versus, for a small number of these, trying to turn
them into a stem cell line that might ultimately teach us
something about human development in medicine and ultimately
help us come up with a treatment for Parkinson's disease or
diabetes or spinal cord injury or some eye disease or liver
disease, which of those is the more ethical choice?
I think it is too easy to simply say, well, the embryo is
an entity that is a potential human and therefore any
consideration of using the word ``research'' in the same
sentence is something we should be opposed to. We are not
really being given that as an alternative. These embryos exist.
They are going to continue to exist as long as in vitro
fertilization goes forward, and it is. And certainly it has
given many couples a chance for a new life in their families.
So putting the reality test here, I believe that most
people who look carefully at the issues, whether from a faith
perspective or a purely humanistic perspective, come up with a
conclusion that what is potential here justifies what we are
talking about in terms of Federal funding of human embryonic
stem cell research.
Senator Harkin. Well, thank you very much for that profound
statement. Thank you very much, Dr. Collins. We have statements
submitted from Senators Murray and Feinstein to be included in
the record.
[The statements follow:]
Prepared Statement of Senator Patty Murray
Thank you, Senator Harkin, for holding this hearing. Stem cell
research is not just about science--it's about hope. The hope of
millions Americans who are suffering from diseases like Alzheimer's,
Parkinson's, and diabetes. The hope of their friends, families, and
loved ones who can't bear to see them in pain another day. And the hope
of a scientific and medical community that is fighting against the
clock to save lives and reduce suffering.
Stem cell research offers this hope because it is one of the most
promising fields in medical research today. And we simply cannot afford
to allow potential cures to be slowed down or halted by the political
process.
That's why I was so glad when President Obama issued an Executive
order in March of last year to lift the restrictions on funding for
human embryonic stem cell research. This action took the handcuffs off
of our scientists and made sure we were exploring every option for
finding cures to debilitating diseases. Because as so many of us know,
limiting Federal support of this research will continue to push
embryonic stem cell research overseas. And our country will continue to
fall behind in a critical, growing, and cutting-edge field.
Because of the arbitrary limits on stem cell research that were
imposed in the past, we are already getting off to a slow start--and we
can't afford to fall any farther behind. Because in addition to helping
patients--cutting-edge research also creates jobs and boosts the
economy.
My home State of Washington is home to world-class research
institutions like the University of Washington and the Fred Hutchinson
Cancer Research Center, just to name a few. They want to help patients.
They want to do this research to help cure debilitating diseases, but
we need to make sure they have the resources they need to succeed. And
that great institutions in Washington State and across the country
continue leading the way in science, research, and medical cures.
Nothing sums this issue up better than a letter I received from a
mom named Suzanne, from Seattle, whose 16-year-old son has diabetes.
She wrote to me and said:
``For our family, embryonic stem cell research offers the hope that
by the time our son finishes graduate school, scientists will be
developing new therapies or even a cure for his diabetes. Every year
that researchers are denied full access to the best cellular material,
and the funds with which to study it, is a year wasted, and a year
denied to my son to live outside the burden of his disease . . . Please
keep hope alive for Charlie, and millions of kids like him.''
Once again, this is about hope.
I am going to keep fighting to make sure this hope stay alive for
Suzanne and millions of others.
And I am going to keep working to make sure nothing stands in the
way of our medical researchers and doctors developing cures and
reducing suffering.
Thank you, again, Senator Harkin, for holding this hearing, and I
look forward to continuing to work with you on this issue.
______
Prepared Statement of Senator Dianne Feinstein
I want to thank Chairman Harkin for calling this hearing today.
Last month, the U.S. District Court for the District of Columbia
issued an alarming decision that temporarily halted Federal funding of
human embryonic stem cell research. That opinion has now been stayed
pending appeal, but it should serve as a wake-up call to us all.
We must do everything we can to protect this funding, which is
essential to lifesaving research innovations.
Human embryonic stem cells have the potential to become any type of
cell in the human body, meaning that the potential for treatment of
disease is unlimited. This kind of research is vital to finding cures
for Alzheimer's, Parkinson's disease, diabetes, spinal cord injuries,
and numerous other illnesses.
National Institutes of Health (NIH) funding of these research
projects holds out the possibility of a cure for millions of Americans.
In the last year alone:
--1.5 million Americans were diagnosed with cancer;
--60,000 Americans were diagnosed with Parkinson's;
--12,000 Americans suffered spinal cord injuries; and
--1.6 million adults were diagnosed with diabetes.
Those are just the new diagnoses--think of all the other Americans
who continue to suffer from cancer, heart disease, Alzheimer's,
Parkinson's, spinal cord injuries, and other catastrophic diseases who
could potentially be helped by embryonic stem cell research.
There is no question but that this research must be conducted
within strict ethical guidelines, and these guidelines must, in my
view, take into account the millions of people whose lives human
embryonic stem cell research may dramatically improve or even save.
President Obama's 2009 Executive order on research involving human
stem cells paved the way for responsible scientific research and
removed critical barriers to potential breakthroughs from this
research.
Under the Executive order, the strictest guidelines were put in
place. Any embryo used must be left over following fertility treatment;
it must be clear that the embryos would otherwise be discarded;
individuals providing the embryos must provide written consent; and the
donors may not be compensated for their donation.
The District Court's decision, and its unprecedented and highly
restrictive interpretation of the Dickey-Wicker amendment, cast all of
this aside and placed in peril hundreds of millions of dollars in
research grants.
If the decision is not overturned:
--50 requests for new NIH research funding will not be considered;
--Roughly 12 requests that were likely to be approved will be frozen;
--22 grants totaling about $54 million that are due for renewal in
September will be cut off; and
--Another 199 grants already awarded for about $131 million will be
at risk next year.
The Justice Department continues to fight the decision, and I,
along with Senators Harkin, Specter, Boxer, and others, are committed
to working to pass legislation in the Senate that ensures that Federal
funding can continue.
The United States has long been a leader in biomedical research and
innovation. We have many of the best and brightest medical researchers
in the world who are working to end suffering from all kinds of
diseases. We should give them every tool we can to advance their work
for the millions of American patients who are hoping and praying that
they will find a cure.
I want to thank Chairman Harkin again for holding this hearing, and
I look forward to working together to protect and promote this vital
research.
Senator Harkin. Now I will introduce our panel here, and
then we will have our testimonies. Dr. George Daley, professor
of Hematology and Oncology at Children's Hospital in Boston and
the Dana Farber Cancer Institute, also professor of Biological
Chemistry and Molecular Pharmacology at Harvard Medical School.
Dr. Daley is past president of the International Society for
Stem Cell Research and chaired the International Task Force
that wrote ethical guidelines for human embryonic stem cell
research. He received his Ph.D. in biology from MIT and his
M.D. degree from Harvard Medical School.
Dr. Sean Morrison, Director of the University of Michigan
Center for Stem Cell Biology, where he is also a professor of
Medicine and a professor in the Life Sciences Institute. Dr.
Morrison is also a director of the International Society for
Stem Cell Research. He received his Ph.D. in immunology from
Stanford University.
Jean Peduzzi Nelson is an associate professor at the
Department of Anatomy and Cell Biology at Wayne State
University School of Medicine. Dr. Peduzzi Nelson received her
B.S. from the University of Michigan and her Ph.D. from Wayne
State University.
Ms. Cody Unser is the founder of the Cody Unser First Step
Foundation, an organization dedicated to raising research funds
and public awareness for people afflicted with spinal cord-
related paralysis. Ms. Unser graduated in May from the
University of the Redlands with a degree in biopolitics. She is
now a graduate student at the George Washington University
School of Public Health studying health policy.
I thank you all for being here today, and I thank you for
your indulgence because of our votes. I will make sure that all
of your statements are made a part of he record in their
entirety. And starting with you, Dr. Daley, working down, if
you could sum up in 5 minutes or so--I will not hold you to an
exact time, but we will start with 5 minutes and try to get it
there so we can open it up for some discussion and questions.
But again, Dr. Daley, no stranger to this subcommittee, welcome
back.
STATEMENT OF GEORGE Q. DALEY, M.D., Ph.D., DIRECTOR,
STEM CELL TRANSPLANTATION; ASSOCIATE
DIRECTOR, STEM CELL PROGRAM, CHILDREN'S
HOSPITAL BOSTON, BOSTON, MASSACHUSETTS
Dr. Daley. Thank you very much. Chairman Harkin, thank you
for the invitation to testify.
I am here to assert that human embryonic stem cells offer
unique advantages for understanding human diseases and are
essential to a vigorous national portfolio of stem cell
research.
However, recent upheavals in the Federal funding are
disrupting our research. They are dissuading scientists from
entering the field and they are threatening American pre-
eminence in the research.
As director of the Stem Cell Transplant Program at
Children's, I wish to first speak to the success we have in
using adult stem cells. And we are using adult stem cells to
cure kids with a variety of life-threatening diseases. We
perform some 80 stem cell transplants per year for childhood
leukemia, genetic diseases, and indeed, we have cured many
kids. I was on rounds last week. I met an adorable little girl.
She was about to receive her transplant for a very rare genetic
immune disorder, and I found out she was the second in her
family that we could very confidently say we would cure. So it
is very, very heartening to save the life of a child.
But I am also here to advocate as a scientist, and as a
scientist I am sobered by the statistic that fewer than half of
all patients treated with stem cells are cured, and despite 50
years of research in adult hematopoietic stem cell transplants
and practice--this is our most successful form of transplant--
blood cancers still relapse and patients still die. So as a
scientist, I am working to improve these treatments through
research on adult stem cells, embryonic stem cells, and iPS
cells.
I think it is a flawed argument to say that scientists
should restrict their focus to adult stem cells, and I think it
is a mistake to cast the different types of stem cells as
competing priorities. Adult stem cells are not better than or
more promising than embryonic stem cells. Embryonic stem cells
are different, and to many scientists, they offer more hope in
certain diseases like diabetes. Would it make sense as a
Federal policy to fund cancer and cardiovascular research but
not diabetes research? All of these are essential research
avenues, and the most successful strategy to advancing cures is
to let scientists decide which cells to study.
Now, I have been a student of the hematopoietic stem cell,
the adult stem cell, for 25 years, but starting about 15 years
ago, I began envisioning a new approach to the research to
generating blood stem cells from embryonic stem cells. And the
idea was that we could generate customized blood stem cells in
a way that would solve the immune rejection problems, solve the
donor shortages, and allow us to perform gene repair, together
with bone marrow transplantation.
Now, we have succeeded in mice, and we have a lot of
promise in humans. In 2007, I was one of three laboratories to
produce iPS cells, and in 2008, my lab produced the first large
repository of human disease-specific iPS cells.
So why, given that I have pioneered the development of both
adult stem cells and iPS cells, do I continue to advocate for
human embryonic stem cells?
Well, there are several reasons, and the first is that iPS
cells and many other future areas of research are founded on
the knowledge we have gained from human embryonic stem cells.
Second, my own research and that of others is pointing to
important differences between iPS and embryonic stem cells.
And third, some diseases are simply more effectively
modeled with human embryonic stem cells than iPS cells. We
recently showed that you could model human Fanconi anemia, a
disease that predisposes kids to leukemia, as well as Fragile X
syndrome, which is the most common genetic cause of autism and
mental retardation, and these were better modeled with human
embryonic stem cells.
So when we have so much to learn from embryonic stem cells,
how can we conclude that we do not need to fund the research?
We are told that restrictions on Federal funding will not
inhibit stem cell research and that private philanthropy will
fill the gap, but realistically research careers are founded on
the architecture of Federal support. Investment by the NIH has
made U.S. research pre-eminent. It has given us domination in
the Nobel Prizes, and it has been an engine for our very
vigorous biotechnology industry.
Now, opponents of embryonic stem cell research will argue
that adult stem cells are more promising, that embryonic stem
cells have yet to cure anyone. Well, this is like arguing why
try to develop new classes of antibiotics when we have got
penicillins and cephalosporins. Let us continue to work to
improve those.
It is very curious. The only time I confront the argument
that adult stem cells are superior and that embryonic stem
cells should be replaced is at hearings like this. At
scientific meetings, we discuss and debate adult and embryonic
and iPS cells as all complementary aspects of cell and
developmental biology.
In my opinion, the arguments that adult stem cells obviate
the need for embryonic stem cells are not scientifically
driven. They are ideologically driven arguments to suppress
embryonic stem cell research. And no matter how much progress
is made with other forms of stem cells, embryonic stem cells
will remain a vital research tool. embryonic stem cells are not
contestants on Survivor that should be voted off the island.
Expelling embryonic stem cells from the researchers' toolkit
will gravely weaken the search for cures.
Now, President Obama's policy has expanded access to more
embryonic stem cell lines, and the court challenge has really
come on us as a major blow. We have had immediate disruptions,
but the long-term uncertainty is even more insidious. And I
have several trainees who have toiled to make their projects on
human embryonic stem cells work, and the uncertainty has really
compelled some of them to abandon those plans. So these
decisions which are driven by politics and not science are
deeply disturbing.
PREPARED STATEMENT
So let me finish by saying that although the injunction has
been stayed, with the latest upheavals, we are again reminded
that human embryonic stem cell research is on fragile and
fickle footing and that new legislation is needed to sustain
the momentum of embryonic stem cell research and to allow
scientists and not politicians and not judges to determine
which research priorities to pursue.
Thank you.
Senator Harkin. Dr. Daley, once again thank you for a very
profound statement and for all the work that you have been
doing in this area.
[The statement follows:]
Prepared Statement of George Q. Daley
Chairman Harkin and distinguished members of the subcommittee,
thank you for the invitation to testify today on the subject of human
embryonic stem (embryonic stem) cells. I am here to assert that human
embryonic stem cells offer unique advantages for understanding a number
of human diseases and are essential to a vigorous portfolio of stem
cell research here in the United States. I also wish to recount how
recent upheavals in Federal funding have disrupted our research and how
ambiguous Federal policy saps the motivation of junior scientists and
threatens American pre-eminence in this vital field of biomedical
research.
My name is George Daley and I am the Samuel E. Lux IV Professor of
Hematology/Oncology and Director of the Stem Cell Transplantation
Program at the Children's Hospital Boston and the Dana Farber Cancer
Institute. I am also Professor of Biological Chemistry and Molecular
Pharmacology at Harvard Medical School, Principal Faculty and founding
member of the Executive Committee of the Harvard Stem Cell Institute,
and an investigator of the Howard Hughes Medical Institute. I am past
president of the International Society for Stem Cell Research (ISSCR;
2007-2008), the major international organization of stem cell
scientists with more than 3,000 members worldwide. I chaired the
international task force that wrote ethical guidelines for human
embryonic stem cell research (ISSCR Guidelines for Human Embryonic Stem
Cell Research 2006) \1\ and as ISSCR President empanelled and
participated in the international task force that wrote guidelines for
the responsible clinical translation of stem cell therapies (ISSCR
Guidelines for the Clinical Translation of Stem Cells 2008.).\2\ I am
here representing the American Society for Cell Biology, whose members
number some 10,000 scientists.
---------------------------------------------------------------------------
\1\ Daley, G.Q., et al., Ethics. The ISSCR guidelines for human
embryonic stem cell research. Science, 2007. 315(5812): p. 603-4.
\2\ Hyun, I., et al., New ISSCR guidelines underscore major
principles for responsible translational stem cell research. Cell Stem
Cell, 2008. 3(6): p. 607-9.
---------------------------------------------------------------------------
As Director of the Stem Cell Transplantation Program at Children's
Hospital I speak as a doctor who uses adult stem cells to treat
patients with life-threatening blood diseases--including leukemia,
sickle cell anemia, immune-deficiency, bone marrow failure, and
others--but I also speak as a scientist working to improve those
treatments through research on adult stem cells, embryonic stem
(embryonic stem) cells, and induced pluripotent stem (iPS) cells. Stem
cell research is important to real live patients, and I believe to my
core that stem cell research offers tremendous promise for curing a
range of diseases. It is a mistake to cast the different types of stem
cells as competing priorities. Adult stem cells are not better than or
more promising than embryonic stem cells. And iPS cells do not obviate
the need for embryonic stem cells. Would it make sense to fund cancer
and cardiovascular research but not diabetes research? All are
essential research avenues. The most successful strategy to advance
stem cell research is to let scientists decide which cells to study.
Let me first speak to the success and the limitations of adult stem
cell therapies. Hematopoietic stem cells harvested from bone marrow,
mobilized peripheral blood, and umbilical cord blood are the most
successful adult stem cell treatments, and potentially curative for
cancers of the blood and some genetic diseases. At Children's we
perform some 80 stem cell transplants per year for childhood leukemia
and conditions like immune deficiency. Casting our success in a
positive light, we have cured many kids over the years. On transplant
rounds last week, I was heartened to meet a little girl about to
receive her transplant for a rare inherited immune condition, the
second in her family that we will likely cure. Saving the life of a
child is deeply gratifying. However, confronting our shortcomings, we
must acknowledge that fewer than half of all patients treated with
hematopoietic stem cell transplants are cured. Despite 50 years of
research and practice in hematopoietic stem cell transplantation, blood
cancers still relapse, and patients still die or become severely
disabled because the transplant regimens are so toxic. Many patients
who might benefit never make it to the transplant stage because they
are too sick or lack a suitable donor.
Such limitations of even our most successful adult stem cell
therapies for blood diseases drive me, as a medical research scientist,
to seek improvements through stem cell research. I have been a student
of the hematopoietic stem cell for 25 years, and I remain an ardent
advocate for research on adult stem cells. But starting more than
fifteen years ago, I began to explore a new approach to bone marrow
transplant based on making blood stem cells from embryonic stem cells.
I envisioned one day generating customized stem cells perfectly matched
to my patients, thus bypassing the challenge of immune matching,
eliminating the problems of donor shortages, and making transplants
safer because they would be performed with a patient's own cells.
Moreover, for patients with genetic diseases, this new approach offered
potentially safer ways to repair gene defects and to return healthy
cells to the patient. Indeed, we have succeeded in treating mice with
genetic immune deficiency with this strategy, and we are making headway
towards the goal of developing similar treatments with human cells.
Opponents of embryonic stem cell research will argue that adult
stem cells are more promising, that embryonic stem cells have yet to
cure anyone, and that with iPS cells in hand, embryonic stem cells are
no longer needed. By similar reasoning, why try to develop new classes
of antibiotics? Let's just keep trying to improve penicillin. The only
time I confront the argument that adult stem cells are superior to
embryonic stem cells and should replace embryonic stem cells is at
hearings like this. At scientific meetings, discoveries with adult and
embryonic stem cells are discussed and debated as integrated and
complementary aspects of cell and developmental biology, not as
contestants on American Idol. In my opinion, such arguments are not
sound scientific advice, but rather ideologically driven attempts to
prohibit scientists from using embryonic stem cells to search for new
cures. No matter how much progress is made with other forms of stem
cells, embryonic stem cells will remain a vital research tool, and any
expulsion of embryonic stem cells from the researcher's toolkit would
gravely weaken stem cell research overall.
Embryonic stem cells are valuable because they are pluripotent,
that is, able to make any tissue in the human body, and can grow
indefinitely in a petri dish. In contrast, adult stem cells show a
restricted potential for generating cells of a given tissue, and are
difficult to propagate in a petri dish and thus available in limited
quantities. Not all tissues regenerate from adult stem cells, which is
a major reason why we need embryonic stem cells. Indeed, in juvenile
diabetes, there is little or no regeneration of the insulin-producing
beta cells that have been destroyed by immune attack. We are
technically capable of transplanting a whole pancreas or isolated
pancreatic islets to replace beta cells, but there is a shortage of
these organs for transplanting even the most severe diabetics.
Consequently, embryonic stem cells are being developed by the
biotechnology company Novocell as an alternate and more readily
available source of beta cells for treatment of diabetes.
Only 3 years ago, a new form of pluripotent stem cell was
introduced into stem cell research, the induced pluripotent stem cell,
popularly called the iPS cell. At the end of 2007, my lab was one of
three worldwide to report the successful derivation of human iPS
cells,\3\ and in 2008, my lab was the first to produce a repository of
customized iPS cells from patients with a range of diseases like
Parkinsons, diabetes, and immune deficiency.\4\ iPS cells share the
defining features of embryonic stem cells-pluripotency and limitless
growth, and one goal of stem cell research is to refine techniques for
making iPS cells that are indistinguishable from embryonic stem cells.
Thus, given that iPS cells exist, why is there a need for human
embryonic stem cells, and what is the value of continued development of
new human embryonic stem cell lines?
---------------------------------------------------------------------------
\3\ Park, I.H., et al., Reprogramming of human somatic cells to
pluripotency with defined factors. Nature, 2008. 451(7175): p. 141-6;
online Dec. 23, 2007.
\4\ Park, I.H., et al., Disease-specific induced pluripotent stem
cells. Cell, 2008. 134(5): p. 877-86.
---------------------------------------------------------------------------
First, it is important to note that the iPS breakthrough was
founded upon the study of embryonic stem cells, and isolation of human
iPS cells depended upon specific culture conditions for human, not
mouse, embryonic stem cells. Today, human embryonic stem cells remain
the gold standard against which our cultures of human iPS cells are
compared. Human embryonic stem cells hold many more secrets, and no one
can be sure where the next breakthrough will emerge.
Second, it is not clear that even ideal iPS cell lines are
identical in all respects to embryonic stem cells. My lab and that of
Konrad Hochedlinger recently demonstrated that iPS cells tend to retain
chemical modifications of their DNA reminiscent of their tissue of
origin, so that when the iPS cells are differentiated in the petri
dish, they reflect a preference to form the tissues from which they
were derived.\5\-\6\ This so-called ``epigenetic memory''
dictates that iPS cells made from blood cells make better blood than
iPS cells made from skin cells. We are working towards ways to erase
these memories, but these data teach us that in practice, iPS cells
harbor important differences from embryonic stem cells that influence
their behavior and potential utility in research and therapy.
---------------------------------------------------------------------------
\5\ Kim, K., et al., Epigenetic memory in induced pluripotent stem
cells. Nature, 2010 online July 19.
\6\ Polo, J.M., et al., Cell type of origin influences the
molecular and functional properties of mouse induced pluripotent stem
cells. Nat Biotechnol, 2010. 28(8): p. 848-55.
---------------------------------------------------------------------------
Third, although iPS cells provide a flexible alternative to
embryonic stem cells in modeling human diseases, not all diseases are
readily modeled with iPS cells. One of the first diseases we attempted
to model with human iPS cells was a fascinating but rare condition
called Fanconi anemia that leaves kids with bone marrow failure and a
predisposition to leukemia and various cancers. Despite repeated
attempts, we have been unable to generate iPS cells from patients with
Fanconi anemia, and last year the laboratory of Juan-Carlos Izpisua-
Belmonte published that Fanconi anemia cells were resistant to iPS
generation.\7\ Mice that lack the same genes as human Fanconi patients
do not develop the same marrow failure and leukemia of human patients.
Thus, we turned instead to modeling Fanconi anemia by depleting the
relevant genes from human embryonic stem cells, and then examining the
effects on human blood formation in the petri dish. Using genetically
modified human embryonic stem cells, we discovered that Fanconi anemia
alters the earliest stages of human embryonic blood development,
teaching us that the condition develops in utero, such that children
are born with stem cell deficiency, a new insight for a condition
thought to develop only later in childhood.\8\
---------------------------------------------------------------------------
\7\ Raya, A., et al., Disease-corrected haematopoietic progenitors
from Fanconi anaemia induced pluripotent stem cells. Nature, 2009.
460(7251): p. 53-9.
\8\ Tulpule, A., et al., Knockdown of Fanconi anemia genes in human
embryonic stem cells reveals early developmental defects in the
hematopoietic lineage. Blood, 2010. 115(17): p. 3453-62.
---------------------------------------------------------------------------
Another example where human embryonic stem cells offer an advantage
over iPS cells is in the study of Fragile X syndrome, the most common
genetic cause of mental retardation. Fragile X is caused by a defect in
the FMR1 gene, which is expressed early in human development, but in
affected individuals becomes aberrantly silent in adult tissues,
including nerve cells. My Israeli colleague, Nissim Benvenisty, had
generated human embryonic stem cells from discarded embryos that
carried the gene defect. When these embryonic stem cells were
differentiated in the petri dish, the gene shut off, just as it does
during human development. In collaboration with the Benvenisty lab, we
asked what would happen to the FMR1 gene in iPS cells made from skin
cells of Fragile X individuals. To our surprise, the gene remained
silent in iPS cells, showing that Fragile X-iPS cells differed from
Fragile X embryonic stem cells, with only the embryonic stem cells
reflecting the dynamic FMR1 gene silencing observed in human
development.\9\ For studying gene silencing in Fragile X, human
embryonic stem cells provide a unique advantage.
---------------------------------------------------------------------------
\9\ Urbach, A., et al., Differential modeling of fragile X syndrome
by human embryonic stem cells and induced pluripotent stem cells. Cell
Stem Cell, 2010. 6(5): p. 407-11.
---------------------------------------------------------------------------
Finally, human embryonic stem cells remain valuable tools for
research. There is still much to be learned about human embryonic stem
cells, and about how stem cells derive from human embryos. Only
recently have we learned that human embryonic stem cells are markedly
different from mouse embryonic stem cells, and represent a distinct
type of pluripotent stem cell. Only recently have we learned that
deriving human embryonic stem cells in reduced oxygen conditions
preserves two active X chromosomes, which is the natural embryonic
state, leaving us to question whether any of the existing human
embryonic stem cells have been derived in an optimal way.\10\ When we
still have so much to learn, how can we conclude that embryonic stem
cells are no longer needed?
---------------------------------------------------------------------------
\10\ Lengner, C.J., et al., Derivation of pre-X inactivation human
embryonic stem cells under physiological oxygen concentrations. Cell,
2010. 141(5): p. 872-83.
---------------------------------------------------------------------------
We are told that restrictions on Federal funding do not inhibit
stem cell research because private philanthropy fills the gap.
Realistically, however, research careers are built upon the
architecture of Federal grant support. Investment by the NIH has made
the United States the pre-eminent incubator for biomedical research,
has produced American dominance in Nobel prizes in medicine, and has
contributed directly to our robust biotechnology industry. Medical
research is one of the chief sectors projecting job growth over the
next decade, and one of the few areas of technological innovation where
U.S. leadership remains largely uncontested. A loss of Federal funding
threatens American competitiveness in stem cell research.
Unfortunately, during the last decade prohibitions and restrictions
on Federal funding for human embryonic stem cell research has greatly
restricted progress and dissuaded numerous scientists from entering the
field. President Bush allowed funding for a very restricted set of
cells--in practice only a small handful--but prohibited funding for the
more than 1,000 human embryonic stem cell lines generated since his
policy was enacted on August 9, 2001. Many of these embryonic stem cell
lines have important advantages for medical research, like carrying the
precise gene defects responsible for human disease. President Obama's
policy has expanded access to many more lines and has succeeded in
bringing many dozens of additional laboratories into the field, as
evidenced by the new grants submitted or approved for research in the
last year.
Against this backdrop of rising enthusiasm after nearly a decade of
frustration for patients, their families, their physicians, and the
research community, the announcement of the injunction against Federal
funding came as a major blow. I was justifiably confused by what the
injunction meant for our research program, which depends heavily on
Federal grant dollars, and personally, I was deeply discouraged and
worried for the future of human embryonic stem cell research.
Several cases illustrate the immediate harm to our research program
and the potential harm to the careers of young scientists by the
current confusion. A doctoral student in my lab has just completed
nearly a year of work mastering a protocol for generating red blood
cells from human embryonic stem and iPS cells, a critical step in her
research on sickle cell anemia. Because of variability among the iPS
lines, human embryonic stem cells are essential for her studies, and
she has just started to have success with the H1 line of human
embryonic stem cells. However, because she is being paid by Federal
dollars and the future prospects are so uncertain, she has abandoned
the use of human embryonic stem cells, and is instead restricting her
efforts to iPS cells that may give sub-optimal red blood cell
production. Such a compromise--driven by politics and not science--is
deeply troubling. Several other scientists in my lab have altered their
projects out of concern for a loss in Federal funding. Two scientists
being funded on Federal training grants abandoned plans to test human
embryonic stem cells for their response to a unique cocktail of growth
factors that had stimulated blood stem cell formation from mouse
embryonic stem cells. Moreover, I face losing my largest NIH grant,
which is aimed at defining the precise similarities and differences
between embryonic stem and iPS cells. I have been scrambling to come up
with private funding so that I don't have to lay anyone off. I wrote to
my seven co-investigators on this project and warned them not to expect
funding for the second year, which would stop cold major new research
collaborations that have already proven remarkably productive.
Scientific research is challenging enough without adding the
uncertainty and fickle nature of Federal support for one's research to
the task.
With the recent upheavals, scientists have again been reminded that
human embryonic stem cell research is on fragile and fickle footing.
The cloud that hangs over the field saps enthusiasm for planning a
long-term program of NIH grant-funded human embryonic stem cell
research, which is the bedrock of most research careers. Younger
researchers are discouraged from entering the field, while established
researchers like myself are spending a disproportionate amount of time
on regulatory compliance, legal interpretation, program management, and
external fundraising. With the economy in turmoil, private funding for
stem cell research has become scarce. Ambiguity about Federal policy
itself has a negative impact that extends beyond the practical
restrictions of legislation. Having devoted the last 25 years of my
career to aspects of adult and embryonic stem cell biology, I am
convinced that human embryonic stem cells are critical to a multi-
faceted portfolio of NIH stem cell research, and in the long run will
save lives. New legislation is needed to sustain the momentum of human
embryonic stem cell research in the United States, and to allow
scientists--not politicians and judges--to determine which research
priorities to pursue.
Senator Harkin. Now we turn to Dr. Morrison. Dr. Morrison,
welcome. Proceed.
STATEMENT OF SEAN J. MORRISON, Ph.D., DIRECTOR, CENTER
FOR STEM CELL BIOLOGY, UNIVERSITY OF
MICHIGAN, LIFE SCIENCE INSTITUTE, ANN
ARBOR, MICHIGAN
Dr. Morrison. Thank you, Senator Harkin, for the
opportunity to testify today.
I have spent my entire career doing stem cell research,
almost exclusively adult stem cell research. The research in my
lab has won a number of awards, including a Presidential Early
Career Award from President Bush in 2003.
Nonetheless, like nearly all leading stem cell researchers,
I believe the Federal Government must support all forms of stem
cell research, including human embryonic stem cells. We simply
do not yet know what kinds of stem cells will yield the
breakthroughs of the future and must pursue all forms of stem
cell research to develop new therapies sooner rather than
later.
Stem cell scientists do not cluster into adult versus
embryonic camps. This framing of the debate comes from
political lobbyists. I interact regularly with hundreds of the
leading stem cell scientists throughout the world, and
virtually all of them believe that research must continue with
all types of stem cells for the reasons George just
articulated.
Stem cell research is a remarkably fast-moving field that
has taken a series of unexpected twists and turns over the past
several years. There is no point in the last 10 years where we
could have predicted even 2 years down the road where the field
would be. Yet, at every point there have been people who
believe they could predict the future and who could tell us
which avenues of research should be abandoned. But until the
research is done, we do not know what the answers will be.
Think about the arguments that opponents have made as
alternatives to embryonic stem cell research.
First, they suggested that umbilical cord blood cells could
replace embryonic stem cells. Yet, my lab has studied cord
blood, and I can tell you that there was never any
scientifically plausible basis for the argument that cord blood
cells could do what embryonic stem cells can do. And you no
longer hear much about cord blood as an alternative.
Instead, they subsequently suggested that amniotic cells
could replace embryonic stem cells, but those cells are
biologically different from embryonic stem cells and, again,
were never a plausible alternative. And again, you never hear
about those cells anymore.
Then opponents circulated lists of more than 70 diseases
they claim could be cured with adult stem cells. What they do
not tell you is that only diseases of the blood-forming system
are routinely treated with adult stem cells and that many of
the other ``treatments,'' in quotation marks, they cite are
highly speculative, are often not based on sound science, and
are prohibited from being sold to patients in this country by
our FDA.
The reality is that many types of stem cells are likely to
yield scientific advances and potentially new therapies. And it
would be foolish to place all of our bets on certain stem cells
at such an early stage in the development of this field.
For this reason, the International Society for Stem Cell
Research has repeatedly recommended that all forms of stem cell
research must be pursued and that patients should be cautious
about claims regarding unproven adult stem cell therapies that
are offered overseas. Where would we be right now if you had
taken the advice of opponents of embryonic stem cell research
and directed the NIH to focus their funding on umbilical cord
blood cells or on amniotic cells? Promising research would have
been abandoned in favor of the alternative du jour, sacrificing
scientific progress and the opportunity to develop new
therapies.
The award my lab received from President Bush was for our
work studying stem cells that give rise to the peripheral
nervous system. One of the things we discovered is that a birth
defect called Hirschsprung disease is caused by defects in the
function of these neural stem cells during fetal development.
In kids with Hirschsprung disease, the neural stem cells fail
to migrate into part of the intestine, rendering that segment
of the intestine nonfunctional. Our work suggested that we
might be able to bypass that defect by transplanting neural
stem cells into the nonfunctional portion of the gut. The
problem is that neural stem cells with the right properties
only exist during fetal development. So we decided to generate
those cells by deriving them from human embryonic stem cells.
Now, I want to emphasize this point because for the therapy
we want to use a tissue-specific stem cell, a cell that in the
newspaper is generally referred to as an adult stem cell. And
yet, we have to obtain it from embryonic stem cells. So this
illustrates why it is scientifically meaningless to frame this
debate as a choice between adult and embryonic stem cells
because we sometimes need embryonic stem cells to derive the
adult cells that we want to use in the therapy.
So this research in my lab is funded by the NIH, but it has
suffered from repeated delays. First, the grant was delayed
while NIH put in place its new embryonic stem cell policy. Then
we received the grant but we were unable to spend the money
until NIH had the opportunity to review and approve new stem
cell lines for funding. And finally, we were able to start the
research, but just 8 months later, the Federal injunction was
issued.
In the first few days after the injunction, I told my lab
that if our funding were cut off, we would abandon our work on
Hirschsprung disease. I have with me today Jack Mosher from my
laboratory. Jack, you might want to stand up for a second. Jack
is the guy in my lab who does this work. The project I have
been telling you about is Jack's work, and his salary comes
exclusively from this grant. Jack has dedicated the last 9
years of his life to studying peripheral nervous system
development, culminating in this project, attempting to
translate the basic science that we have done to the benefit of
patients. Yet, in those early days after the injunction, Jack
did not know whether his work would survive the injunction,
whether he would still have a salary, or what would happen to
his career.
PREPARED STATEMENT
So I would just sum up by saying that American science is
the envy of the world because it is a meritocracy in which
there is fierce competition to fund the best ideas. If we
accept the principle that those who are not judged to have the
best ideas can obtain judicial relief that blocks funding of
the best ideas to allow the lesser ideas to compete, this will
erode the very heart of American competitiveness. We owe more
to the patients suffering from incurable diseases. We owe it to
them to support all forms of stem cell research so that no
matter where the science leads and where the cures come from,
we can follow the most promising avenues of discovery.
So I would urge you to clarify the Dickey-Wicker amendment
so there can be no question regarding Congress' intent to fund
the most meritorious science.
Senator Harkin. Thank you very much, Dr. Morrison.
[The statement follows:]
Prepared Statement of Sean J. Morrison
My name is Sean Morrison and I'd like to begin by thanking Senator
Harkin and the members of the subcommittee for inviting me to testify.
By way of introduction, I am the Director of the University of Michigan
Center for Stem Cell Biology, where I am also the Henry Sewall
Professor of Medicine, a Professor in the Life Sciences Institute, and
a Professor of Cell and Developmental Biology. I am also an
Investigator of the Howard Hughes Medical Institute, a Director of the
International Society for Stem Cell Research, and a member of the
American Society for Cell Biology Public Policy Committee.
I have spent my entire career doing stem cell research, almost
exclusively adult stem cell research. The adult stem cell research in
my laboratory has won many awards, including a Presidential Early
Career Award from President Bush in 2003. Nonetheless, I'm here today
to tell you that like nearly all leading stem cell researchers, I
believe that the Federal Government must support all forms of stem cell
research, including human embryonic stem cell research. We simply do
not yet know what kinds of stem cells will yield the scientific
breakthroughs of the future or what kinds of stem cells will yield new
treatments for disease. Therefore, we must pursue all forms of stem
cell research in order to have the greatest chance of developing new
therapies sooner rather than later.
Stem cell scientists do not cluster into ``adult'' versus
``embryonic'' camps--this framing of the debate comes from political
lobbyists. I interact regularly with hundreds of leading stem cell
scientists from all over the world and virtually all of them believe
that research should continue with all types of stem cells.
Stem cell research is a remarkably fast-moving field that has taken
a series of unexpected twists and turns over the past several years.
There is no point over the past 10 years during which we could have
predicted where the field would be, even two years down the road. Yet,
at every point there have been people who believed that they could
predict the future and could tell us which avenues of research should
be abandoned. But until the research is done, we don't know what the
answers will be.
Think about the alternatives that have been offered by opponents of
embryonic stem cell research.
--First, they suggested that umbilical cord blood could replace
embryonic stem cells. Yet as somebody whose laboratory has
studied umbilical cord blood I can tell you that there was
never any scientifically plausible basis for suggesting that
cord blood cells could replace embryonic stem cells. The
opponents of embryonic stem cell research never talk about cord
blood anymore.
--Instead, they subsequently suggested that amniotic cells identified
by Dr. Anthony Atala could replace embryonic stem cells. But
those cells are biologically different from embryonic stem
cells and were never a plausible alternative. Even Dr. Atala
has gone on record stating they are not an alternative to
embryonic stem cells. Again, you never hear about those cells
anymore.
--Then, opponents of embryonic stem cell research circulated lists of
more than 70 diseases they claimed could be cured with adult
stem cells. What they don't tell you is that only diseases of
the blood-forming system are routinely treated with adult stem
cells, and that many of the other ``treatments'' they cite are
highly speculative and often not based upon sound science.
--Most recently, opponents of embryonic stem cell research have
suggested that reprogrammed adult cells, so-called iPS cells,
should be studied instead of embryonic stem cells. While these
reprogrammed cells are very promising, George Daley and others
have recently shown that their properties are somewhat
different from embryonic stem cells.
The reality is that all of these types of stem cells are likely to
yield scientific advances, and potentially new therapies, but it would
be foolish to place all of our bets on a single type of stem cell at
such an early stage in the development of this field. For this reason
the International Society for Stem Cell Research, a society
representing thousands of stem cell scientists all over the world, has
repeatedly recommended that all forms of stem cell research must be
pursued, including adult and embryonic stem cells, and that patients
should be cautious about claims regarding unproven adult stem cell
therapies.
Where would we be right now if you had taken the advice of
opponents of embryonic stem cell research and directed the National
Institutes of Health (NIH) to focus their funding on umbilical cord
blood cells or amniotic cells? Promising research would have been
abandoned in favor of the alternative du jour, sacrificing scientific
progress and the opportunity to develop new therapies. We remain unable
to predict the future. So blocking Federal funding for embryonic stem
cell research at this juncture will certainly block scientific progress
and will likely delay the search for new therapies.
The Presidential Early Career Award that my lab received was for
our work studying the stem cells that give rise to the peripheral
nervous system. One of the things we discovered is that a birth defect
called Hirschsprung disease is caused by defects in the function of
these peripheral nervous system stem cells during fetal development.
Hirschsprung disease affects 1 in 5,000 newborns and is caused by a
defect in the development of the portion of the peripheral nervous
system that regulates intestinal function. In kids that have
Hirschsprung disease, the neural stem cells fail to migrate into the
large intestine, rendering that segment of intestine nonfunctional
because of the lack of nervous system in that segment. Surgery to
remove the nonfunctional segment of intestine can save these kids'
lives, but for many of these kids, their guts never quite work right,
leading to life-long problems.
We figured that if Hirschsprung disease is caused by a failure of
stem cells to migrate into the large intestine, that we might be able
to by-pass this migratory defect by transplanting stem cells into the
nonfunctional portion of gut, and that this cell therapy might improve
the treatment of kids with Hirschsprung disease. The problem is that
neural stem cells with the right properties to correctly innervate the
intestines only exist during fetal development. So where would we get
the neural stem cells for therapy? We don't want to use aborted human
fetal tissue. George Daley's recent results have raised the concern
that if reprogrammed adult cells are not generated from peripheral
nervous system stem cells that they might have difficulty making the
correct types of neural cells to regulate intestinal function. Thus,
the most prudent way of generating peripheral nervous system stem cells
is by deriving them from human embryonic stem cells.
I want to emphasize this point--we wish to use tissue-specific stem
cells (often described as ``adult'' stem cells in the newspaper) for
the therapy, but we will obtain them from embryonic stem cells. This
illustrates why it is scientifically meaningless to frame this debate
as a choice between adult and embryonic stem cells. We sometimes need
embryonic stem cells to generate adult cell types for therapy.
We are funded by the National Institutes of Health (NIH) to try to
develop a cell therapy for Hirschsprung disease, using human embryonic
stem cells to derive neural stem cells for transplantation. But our
research has suffered from repeated delays. First, the awarding of this
grant was delayed while NIH put in place its new embryonic stem cell
research policy, after the repeal of the Bush administration policy.
After the new NIH policy was established, we received the grant, but
were unable to spend any of the money until NIH had the opportunity to
review and approve embryonic stem cell lines for funding. Finally,
lines were approved and we were able to start the research, then just 8
months later the injunction was issued.
In the first few days after the injunction was issued none of us
knew exactly what research would be blocked, or how the ruling would be
interpreted by NIH. During this period, I told my lab that if our
funding were cut off as a result of the injunction, and if the
injunction could not soon be lifted, that we would abandon our work on
Hirschsprung disease. I have with me today Jack Mosher from my
laboratory. The project I have been telling you about is Jack's work,
and his salary comes almost exclusively from this grant.
Jack completed his undergraduate work at Allegheny College in
Pennsylvania, then a Ph.D at the University of North Carolina. He came
to my lab in 2001 as a postdoctoral fellow and was ultimately promoted
into a faculty position at the University of Michigan. He has dedicated
the last 9 years of his life to studying peripheral nervous system
development, culminating in this project, trying to translate our
results to help patients. Yet in those early days after the injunction
he did not know whether his work would survive the injunction, whether
he would still have a salary, or what would happen to his career. Since
the injunction, many students, postdoctoral fellows, and junior faculty
have had similar conversations in scores of laboratories across the
country.
It turns out that because of the timing of our annual review, we
received our second year of funding just before the injunction. As a
result, our funding was not interrupted. But this is not the way in
which funding decisions for medical research should be determined.
American science is the envy of the world because it is a meritocracy
in which there is fierce competition to fund the best ideas. As a
consequence, American scientists lead the world in virtually every
measure of scientific impact and America is the world's engine of
scientific discovery.
If we accept the idea that those who do not have the best ideas can
obtain judicial relief that blocks NIH funding for the best ideas, to
help the lesser ideas compete, this will erode the very heart of
American competitiveness.
We don't know yet whether the cell therapy we are attempting to
develop will work, or whether it will ultimately be performed with
embryonic stem cells, reprogrammed adult cells, or other cells. That's
why they call it research. The point is that we're never going to find
out until we do the research. Yet instead of devoting ourselves to
trying to make a difference for kids with Hirschsprung disease, Jack
and I now find ourselves talking about the uncertain future of
embryonic stem cell research, whether legislative and judicial delays
will continue on-and-off indefinitely, and whether his career would be
better served by working in a different area.
I'd like to leave you with one last story. Opponents of embryonic
stem cell research frequently repeat the argument that this research is
less promising than adult stem cell research because adult stem cells
are already used to treat patients whereas embryonic stem cells are
not. The problem is that adult stem cells have been studied for decades
while we have only had human embryonic stem cells since 1998, 12 years.
So let's examine this argument for a moment.
The adult stem cell therapy that is routinely used clinically is
blood-forming stem cell transplantation (formerly known as bone marrow
transplantation) to restore the blood forming systems of patients after
cancer therapy or to treat various diseases of the blood-forming
system. This is indeed a great success: while it's not perfect it does
save thousands of lives each year. What did it take to get to this
point?
After many years of research, the first bone marrow transplant
among unrelated patients was attempted in 1955 by Donnall Thomas. All
of the patients died. Dr. Thomas went back to the laboratory to figure
out why he couldn't just randomly transplant bone marrow cells from one
patient into another. He discovered that donor and recipient had to be
matched, so that their immune systems didn't attack each other. The
first successful bone marrow transplant between an unrelated donor and
recipient was performed in 1969--14 years later. Thus if we were to
take the advice of opponents of embryonic stem cell research, and
abandon lines of research that do not lead to cures within 12 years,
none of the adult stem cell therapies that they exalt would exist today
and Donnall Thomas would never have won the Nobel prize.
Science takes time, and the path to cures is uncertain and fraught
with setbacks. American science is the envy of the world because it has
fostered creativity and innovation, amidst constant competition and
peer review to invest the public's limited resources in the most
promising ideas. We owe nothing less to the patients suffering from
incurable diseases. For this reason, we must support all forms of stem
cell research so that no matter where the cures come from, we can get
there sooner rather than later. I urge you to clarify the Dickey-Wicker
amendment so that there can be no question regarding Congress' intent
to fund the most meritorious science.
Senator Harkin. Dr. Mosher, welcome, and thank you. I may
even have a question for you when we get to the questions here.
Now we turn to Dr. Peduzzi Nelson and welcome and please
proceed.
STATEMENT OF JEAN PEDUZZI NELSON, Ph.D., ASSOCIATE
PROFESSOR, DEPARTMENT OF ANATOMY AND CELL
BIOLOGY, WAYNE STATE UNIVERSITY SCHOOL OF
MEDICINE, DETROIT, MICHIGAN
Dr. Peduzzi Nelson. Thank you very much, Chairman Harkin,
for the opportunity to present this information today.
I am a translational neuroscientist from Wayne State
University, and today I am--there are two types of stem cells,
embryonic stem cells from embryos and adult stem cells. Today I
am going to talk about adult stem cells, and we use the term
``adult stem cells'' to mean not just stem cells from adults,
but also from children, umbilical cord, from blood.
What you have to understand is that the first human adult
stem cell was isolated in 1992. Now, we do have a long history
of doing bone marrow transplants, which contain stem cells, but
adult stem cells are actually, in terms of looking at other
diseases and injuries, a new field. And it was only in the late
1990s did we realize the potential for other diseases other
than cancer and various blood disorders.
Yes, most of the Federal funding does go to adult stem
cells, but the majority of that goes to old but very important
studies in terms of treating cancer and blood diseases. The big
disadvantage for adult stem cells is often there is not
intellectual property. So the biotech industry that has a much
larger budget for research than Federal funding is not
interested in most cases in adult stem cells. And we only have
a limited amount of Federal funding available.
And where we are in adult stem cells--I am sure the members
have seen previously that there are some examples of people
being treated with adult stem cells where there is considerable
improvement. But the research is going from isolated incidents,
and I am going to present clinical trial data in respectable
journals where we need to move through clinical trials to
standard of care. And to move from a basic science study is
relatively inexpensive, several hundred thousand dollars, but
for each clinical trial, you need billions of dollars. So we
need a lot more Federal support to move forward with adult stem
cells.
This is an example of one of the patients. Well, this would
have been an example of one of the patients that was treated, a
quadriplegic that was treated, using a procedure that was
developed in Portugal by Dr. Carlos Lima and his team. And this
is a picture. I think we do have a poster of this gentleman
that I met several years ago. And he was treated with his own
adult stem cells 2 years after his injury. And 2 years after
his injury, this gentleman is now shown standing up without
anyone supporting him. He is not waving, but he was in the
video. And with only braces on his--a foot ankle brace. So he
is standing up maintaining balance, and he can now walk with a
walker. Amazing, a quadriplegic walking with a walker without
assistance, and this is the progress.
But this is not an isolated incident. If you look at the
two publications that have been published in peer-reviewed
journals----
Senator Harkin. Dr. Peduzzi, could I just interrupt for a
quick question?
Dr. Peduzzi Nelson. Yes.
Senator Harkin. Was he treated with what I would refer to
as autologous stem cells?
Dr. Peduzzi Nelson. Yes, he was. And these autologous stem
cells were obtained from inside of his nose and used to treat
his spinal cord injury.
But this, as I said, is not an isolated incident. There are
peer-reviewed publications and a larger number of patients, and
I would love the opportunity to bring this forward in the
United States after completing a safety study so patients do
not have to go to other countries to have this done.
Another example. This is Doug Rice, and he had several
heart attacks and had chronic heart failure. And he was told in
2002 that he had 2 years to live. He went to another country
and had a treatment done, and he is alive and doing well. At
the time he had the procedure done, he could barely walk. But
this is also not an isolated example.
This is a published, peer-reviewed article of a study where
they used 191 patients who had adult stem cells and compared to
200 patients with similar heart conditions. And the treated
patients lived longer and also could exercise more.
Now, I have to move to a somewhat gross picture, and I
apologize for that. But this is corneal blindness, and this is
the second leading cause of blindness in the country. And on
the left side, it shows eyes of patients who had several
surgeries that were unsuccessful and were blind in that eye.
But using adult stem cells from their other eye, this shows the
results several years later. This particular one was 112
patients, and more than 75 percent of the time it was
successful. And many of the patients regained normal vision in
their eye.
And let me just go to another example. This is the study,
the published study, that was published of these 112 patients
in the New England Journal of Medicine.
I will go to one more patient. I am showing these sort of
poster patients or poster examples, but now they are supported
by results from clinical trials. In the middle between his
parents is Joe Davis, and he had very severe sickle cell anemia
and his parents were told that Joe might not live to his teens.
So he had the procedure using his brother's umbilical cord
blood cells, and Joe is absolutely doing fine right now and has
no sickle cell symptoms.
There have been two published studies for sickle cell,
which is a very painful condition. This first study, 6 out of 7
patients no longer have sickle cell symptoms.
And another study--this particular study was by NIH
scientists and published in the New England Journal of Medicine
in 10 adults with sickle cell anemia. Most of these patients--9
out of 10 of these patients--no longer had sickle cell
symptoms.
The last patient that I would like to show is Barry Goudy
and he had MS. He went to Northwestern Memorial Hospital. His
symptoms of MS have disappeared. And he was part of a larger
study that was published in a peer-reviewed journal, in Lancet,
and these patients showed significant functional improvement
and no one got worse in this degenerative disease.
Senator Harkin. Dr. Peduzzi Nelson, I have to ask you to
wrap up. I would like to get to the last--we just have some
more votes that just----
PREPARED STATEMENT
Dr. Peduzzi Nelson. Okay. This is just another study
supporting that. I will not talk about the amazing results in
newly diagnosed juvenile diabetes in JAMA.
But I would just like to conclude that we need more Federal
funding. We need more NIH funding so patients do not have to go
to other countries and so these amazing results that I
presented can go to clinical trials and become standard of care
for U.S. patients that need their support.
Senator Harkin. Thank you very much, Dr. Peduzzi Nelson.
[The statement follows:]
Prepared Statement of Jean Peduzzi Nelson
Thank you Chairman Harkin, Senator Cochran, and distinguished
subcommittee members for the opportunity to present this information to
you today. My name is Jean Peduzzi Nelson from Wayne State University.
Please note that the testimony I am giving today is my own opinion and
not necessarily that of the university. I am a translational
neuroscientist who is working to bring using one's own olfactory
mucosal adult stem cells for spinal cord injury, head injury, and
radiotherapy damage.
There are two major categories of stem cells: embryonic and adult.
Human embryonic stem cells are derived from human embryos and remain
controversial. I want to focus my comments on the science of adult stem
cells that are treating patients for many diseases. This second
category of stem cells can be obtained from adult tissues, as well as
tissues from children. For my purposes, I will use ``adult stem cells''
to refer to these as well as stem cells from umbilical cord blood.
I wanted to share with you pictures of some brave pioneers who
first explored the potential of adult stem cell treatment. The progress
of adult stem cells has gone so far beyond these particular patients to
long-term follow-up results of numerous patients in peer-reviewed
published clinical trials.
Stem cells are cells that can generate lots of cells and, under the
right conditions, become one of the many cell types in the body. Adult
stem cells are stem cells obtained from adults, children, even infants
and umbilical cord after birth. These include cells from the bone
marrow, nose, fat tissue, umbilical cord, and other places. The great
thing about these cells is that a person's own cells can be used which
eliminates the problem of immune rejection and tumor formation
sometimes observed with other types of stem cells. Adult stem cells are
the best stem cells to replace lost or damaged cells in our bodies.
The financial challenge with adult stem cells is that usually when
you use your own cells, there is no intellectual property or patents.
So, the biotech industry that invests billions in research often does
not fund this research.\1\ Millions of dollars are needed to complete
each clinical trial so all patients can benefit from a treatment, not
the lucky few, and so that billions can be saved in healthcare costs.
The National Institute of Health (NIH) has developed new programs to
encourage translational research and clinical trials, but has a much
smaller budget than private industry.\2\ Much of the funding for adult
stem cells by NIH is directed at older, but important uses of bone
marrow stem cells that were developed in the 1950s and 1960s for
leukemia and other cancers. While bone marrow transplants have been
used in patients for years, the successful isolation and
characterization of adult stem cells is a very recent science. The
first mouse adult stem cell was successfully isolated and purified in
the laboratory in 1983.\3\ The first human adult stem cell was first
successfully isolated and characterized in the laboratory in 1924.\4\
New uses of adult stem cells for other diseases and injuries only
started in the 1990s, but have already reached patients with various
diseases and injuries as I will demonstrate.
---------------------------------------------------------------------------
\1\ ``In 2004, the top twenty companies spent a combined total of
over $56 billion on research and development.'' York University (2008,
January 7). Big Pharma Spends More On Advertising Than Research And
Development, Study Finds. ScienceDaily. Retrieved September 10, 2010,
from http://www.sciencedaily.com-/releases/2008/01/080105140107.htm.
\2\ ``. . . growth in the National Institutes of Health (NIH)
budget would slow sharply to just 2.7 percent in fiscal year 2004 from
just-approved fiscal year 2003 level, to $27.9 billion.'' NIH Budget
Growth Slows to 2 Percent in fiscal year 2004, AAAS R&D Funding Update
on R&D in the fiscal year 2004 NIH Budget--REVISED AAAS Report XXVIII:
Research and Development fiscal year 2004, http://www.aaas.org/spp/rd/
nih04p.pdf.
\3\ Spangrude GJ, et al., Purification and characterization of
mouse hematopoietic stem cells, Science 241, 58 (1988).
\4\ Baum CM, et al., Isolation of a candidate human hematopoietic
stem-cell population, Proc. Natl. Acad. Sci. USA 89, 2804 (1992).
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I would like to tell you about five patients who have been helped
by adult stem cells. These patients were either part of a clinical
trial, and their results are now published in a peer-reviewed journal,
or sometimes a similar procedure was done in a clinical trial that is
now published.
The first patient is Silvio who I met several years ago. I have
been working with a group in Portugal led by Dr. Carlos
Lima.\5\-\6\ Dr. Lima, Dr. Pratas-Vital, Dr. Escada, Dr.
Capucho, and Dr. Hasse-Ferreira have been using a person's own tissue
from inside of the nose as a way of delivering adult stem cells. Silvio
had a spinal cord injury at the base of his neck [cervical level 6/7,
American Spinal Injury Association Impairment Scale (AIS) A, complete
injury. Grade A is considered the worst, which indicates a ``complete''
spinal cord injury where no motor or sensory function is preserved in
the sacral segments S4-S5.]. Silvio was left with no movement of his
legs and minimal movement of his fingers. At 2 years after injury, he
received his own adult stem cells and partial scar removal after
intensive rehab failed to lead to an improvement.
---------------------------------------------------------------------------
\5\ Lima, C., P. Escada, J. Pratas-Vital, C. Branco, C.A.
Arcangeli, G. Lazzeri, C.A.S. Maia, C. Capucho, A. Hasse-Ferreira, and
J.D. Peduzzi (2010) Olfactory Mucosal Autografts and Rehabilitation for
Chronic Traumatic Spinal Cord Injury. Neurorehab & Neural Repair 24:10-
22.
\6\ Lima, C., J. Pratas-Vital, P. Escada, A. Hasse-Ferreira, C.
Capucho and J.D. Peduzzi. Olfactory mucosa autografts in human spinal
cord injury: a pilot clinical study, J Spinal Cord Medicine, 29(3):191-
203, 2006.
Today he can maintain standing position and wave without help. With
a walker and short braces, he can walk more than 30 feet without anyone
helping him. He can now move his fingers, which he could not do before.
Because he was in a wheelchair for 2 years before treatment and could
only move the chair using his wrists, a special rehab program called
BIONT (brain initiated non-robotic/non-weight supported training) was
used at Centro Giusto in Italy so he could learn to walk again. Dr.
Arcangeli and Dr. Lazzeri have developed an effective rehab program
that, when combined with adult stem cells, helps patients recover.
BIONT therapy is being used on some U.S. patients who had this
procedure in Portugal at Walk the Line in Detroit. With NIH and/or the
Department of Defense (DOD) I would like to bring olfactory mucosal
stem cell treatment to the people in the United States.
This is much more remarkable than a treatment of an acute spinal
cord injury within the first few weeks after injury. More than 15
percent of the patients who are American Spinal Injury Association
Impairment Scale (AIS) grade A improve in their classification in the
first year after injury.\7\ If a treatment is given acutely or
subacutely, it is difficult to separate normal recovery and effects of
a treatment unless a large number of patients are enrolled in the
clinical trial and randomly assigned to treatment or control. If a
treatment is given at 1 year or greater after spinal cord injury, only
5.6 percent of AIS A (32/571 patients) improve in grade from year 1 to
year 5 after spinal cord injury.\8\
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\7\ Marino RJ, Ditunno JF Jr, Donovan WH, Maynard F Jr. Neurologic
recovery after traumatic spinal cord injury: data from the Model Spinal
Cord Injury Systems. Arch Phys Med Rehabil. 1999;80(11):1391-6.
\8\ Kirshblum S, Millis S, McKinley W, Tulsky D. Late neurologic
recovery after traumatic spinal cord injury. Arch Phys Med Rehabil
2004;85:1811-7.
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Silvio is not an isolated case. Here are the two peer-reviewed
publications from the Journal of Spinal Cord Medicine and
Neurorehabilitation and Neural Repair which reveal that more than half
of AIS A patients improved in grade compared to the normal 5 percent
without treatment. When the adult stem cells are combined with an
effective rehab program, 12/13 AIS A improved in AIS grade and all of
the patients regained some muscle movement in their legs. These
findings were documented with EMG and SSEP recordings.
The next picture is Doug Rice who was told in 1998 that he had 2
years to live due to chronic heart failure after multiple heart
attacks. At that time he could hardly walk. He did not qualify for any
U.S. clinical trials, so he went to Thailand to have a treatment with
adult stem cells. The cells were sent to a company in Israel where the
cells were purified and allowed to multiply, then sent back to Thailand
for injection. Since that time, he has more energy and is enjoying
life. However, this is also not an isolated incident. This year an
article was published in the European Journal of Heart Failure
reporting the followup of 191 patients who received adult stem cells
from their own bone marrow compared to 200 patients with comparable
symptoms.\9\ These adult stem cell treated patients lived longer and
had a greater capacity to do exercises. Their heart functioned much
better based on a large number of tests (left ventricular ejection
fraction, cardiac index, oxygen uptake, and left ventricle
contractility). This report of the STAR-heart study provides the
controlled clinical trial data, and new trials are now proceeding in
the United States.
---------------------------------------------------------------------------
\9\ Strauer BE, Yousef M, Schannwell CM. The acute and long-term
effects of intracoronary stem cell transplantation in 191 patients with
chronic heARt failure: the STAR-heart study. Europ. J Heart Failure
(2010)12:721-29.
I have to apologize for the next picture. It isn't a photo of a
single patient, but somewhat gross pictures of the eyes of three
patients with corneal blindness from an article just published in the
New England Journal of Medicine.\10\ Corneal disease is the second
leading cause of blindness after cataracts in the world.\11\ Corneal
transplants are commonly used, but the transplants are rejected in
about 20 percent of the cases.\12\ On the left are pictures of the eyes
of patients who had severe burns or damage to their eye and suffered
from corneal blindness. These patients had surgery on their eyes, but
these surgeries did not help. Several years later, adult stem cells
were removed from the opposite eye and implanted in the damaged eye.
The results of the adult stem cell transplant are shown on the right
several years after the procedure. The patients went from barely being
able to see hand movements to normal sight in these eyes. This
procedure was successful in more than 75 percent of the 112 patients.
Some of these patients were followed for 10 years. We need more
clinical studies in the United States to treat U.S. patients with
corneal blindness.
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\10\ Rama, P, S. Matuska, G. Paganoni, A. Spinelli, M. De Luca and
G. Pellegrini. Limbal Stem-Cell Therapy and Long-Term Corneal
Regeneration N Engl J Med 2010; 363:147-55.
\11\ Whitcher, JP, M. Srinivasan, & MP Upadhyay. Corneal blindness:
a global perspective. Bulletin of the World Health Organization, 2001,
79 (3):214-221.
\12\ Facts About The Cornea and Corneal Disease, NIH, National Eye
Institute http://www.nei.nih.gov/health/cornealdisease/#4.
The next patient is Joe Davis, Jr. Joe is the boy between his mom
and dad; he was born with severe sickle cell anemia. Sickle cell anemia
is a blood disease that affects 1/500 African Americans. The doctors
thought that Joe might not live to see his teens. When Joe was 2 years
old in 2002, he received a transplant of stem cells from his younger
brother's umbilical cord. Joe no longer has sickle cell anemia. So,
where are we now? About 72,000 people in the United States have sickle
cell anemia that causes pain, chronic tiredness from anemia and severe
infections, usually beginning when they are babies.\13\ In a published
study last year in the New England Journal of Medicine that was
supported by NIH, 10 adults were treated with adult stem cells from
their brother or sister. Of these patients, nine no longer had symptoms
of sickle cell anemia and were doing well at 4 years after their
treatment.\14\ A similar study was published in 2008 showing that 6/7
of the children with severe sickle cell anemia treated in a similar
manner were without sickle cell symptoms when they were examined at 2-8
years after treatment.\15\ It would be great if we could have everyone
with sickle cell anemia treated.
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\13\ Anemia, sickle cell, http://www.ncbi.nlm.nih.gov/bookshelf/
br.fcgi?book=gnd&part= anemiasicklecell.
\14\ Hsieh, MM, EM Kang, CD Fitzhugh, Allogeneic hematopoietic
stem-cell transplantation for sickle cell disease. N Engl J Med
2009;361:2309-2317.
\15\ Krishnamurti L, Kharbanda S, Biernacki MA, Zhang W, Baker KS,
Wagner JE, Wu CJ. Stable long-term donor engraftment following reduced-
intensity hematopoietic cell transplantation for sickle cell disease.
Biol Blood Marrow Transplant. 2008 Nov;14(11):1270-8.
The last picture is Barry Goudy who was suffering from multiple
sclerosis (MS). He had numerous relapses and the medication was not
helping his condition. He was part of a study conducted at Northwestern
Memorial Hospital in Chicago and received his own stem cells in 2003.
His MS symptoms disappeared in 4 months, and he continues to be symptom
free today. Results were published last year by Burt and colleagues in
Lancet.\16\ Patients had what is known as relapsing-remitting MS. These
were patients who were still having relapses despite interferon beta
treatment. All of the treated patients did not show the normal
progressive worsening associated with MS, and a significant functional
improvement was noted in these patients. In a similar study published
this year, they describe the 1-year followup of six patients who showed
improvement when their muscles were evaluated using
electrophysiology.\17\ Their condition either stayed the same or
improved in a disease that is characterized with progressive decline in
function.
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\16\ Burt RK, Y Loh, B Cohen, D. Stefosky et al., Autologous non-
myeloablative haemopoietic stem cell transplantation in relapsing-
remitting multiple sclerosis: a phase I/II study. The Lancet
Neurology--1 March 2009 (Vol. 8, Issue 3, Pages 244--253.
\17\ Rice, CM, E A Mallam, A L Whone, P Walsh, D J Brooks, N Kane,
S R Butler, D I Marks and N J Scolding. Safety and feasibility of
autologous bone marrow cellular therapy in relapsing-progressive
multiple sclerosis. Clinical Pharmacology and Therapeutics, May 5, 2010
DOI: 10.1038/clpt.2010.44.
The five pictures and their related clinical trials using adult
stem cells show amazing progress for severe spinal cord injury, chronic
heart failure, corneal blindness, sickle cell anemia, and multiple
sclerosis. However, this is not an exhaustive list of the recent
clinical trial findings using adult stem cells. I would just like to
mention the amazing progress using adult stem cells in juvenile
diabetes. A recent clinical trial report \18\ in the Journal of the
American Medical Association found that the majority of the 23 patients
who received adult stem cells achieved insulin independence in the 2-
year followup. Many may remember the news report of the person who
received a new trachea using adult stem cells. An article published
this year details the recovery of 20 patients with upper airway
problems that received adult stem cells.\19\ Another break-through
article was published this year in Blood which calls the use of adult
stem cells ``. . . the gold standard in the frontline therapy of
younger patients with multiple myeloma because it results in higher
complete remission (CR) and longer event-free survival than
conventional chemotherapy.\20\
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\18\ Couri CE, Oliveira MC, Stracieri AB, Moraes DA, Pieroni F,
Barros GM, Madeira MI, Malmegrim KC, Foss-Freitas MC, Simoes BP,
Martinez EZ, Foss MC, Burt RK, Voltarelli JC. C-peptide levels and
insulin independence following autologous nonmyeloablative
hematopoietic stem cell transplantation in newly diagnosed type 1
diabetes mellitus. JAMA. 2009 Apr 15;301(15):1573-9.
\19\ Macchiarini P, Rovira I, Ferrarello S. Awake upper airway
surgery. Ann Thorac Surg. 2010 Feb;89(2):387-90; discussion 390-1
\20\ Blade J, Rosinol L, Cibeira MT, Rovira M, Carreras E.
Hematopoietic stem cell transplantation for multiple myeloma beyond
2010. Blood. 2010 May 6; 115(18):3655-63.
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Only with the help of NIH and the DOD Congressionally Directed
Medical Research Programs, can these successful treatments reach all
the people that desperately need them. I applaud Senator Harkin's
efforts to increase the NIH budget in the past and ask all of the
Senators and Representatives to make the people with diseases and
injuries a major priority and put the patients first when considering
funding stem cell research. These pioneers need to be joined by many
other people to help those suffering from diseases and injuries. Adult
stem cells aren't just showing great promise, but are treating people
now. Much more of the limited funding needs to be directed at adult
stem cells that are showing success right now.
Senator Harkin. And now, Ms. Unser, welcome and please
proceed.
STATEMENT OF CODY UNSER, FOUNDER, CODY UNSER FIRST STEP
FOUNDATION, WASHINGTON, DC
Ms. Unser. Thank you, Chairman Harkin, for allowing me to
testify and use my voice on behalf of millions of Americans
living with debilitating diseases. I feel very honored and, to
be honest, frustrated as to why we are here today.
Ten years ago, my hero, my superman, Christopher Reeve, sat
in his power wheelchair and using every breath he took, thanks
to a machine, testified to Congress with the hope that
embryonic stem cell research would be federally funded. Today
in 2010 we are still fighting for this promising and hopeful
research to continue.
Embryonic stem cells are science based on hope, hope for
improving the quality of life of millions of Americans by
providing better treatment and eventually cures.
My journey began 11 years ago. I was a healthy, 12-year-old
kid who was very active and had big dreams. Everything changed
on February 5, 1999. I cannot recall how it felt to put my feet
on the floor, how I got dressed that morning, or what I had for
breakfast, but what I do remember is that in a matter of 20
minutes my body became paralyzed and my life drastically
changed. I was playing basketball at school and suddenly could
not catch my breath and my head started pounding with sharp
pain. The school I was attending called the ambulance and while
laying down in the locker room, my left leg became numb and
tingly. I picked it up, put it back down, and I could not feel
the floor. I was scared out of my mind, but I thought that
whatever was wrong the doctors could fix.
Transverse myelitis is an autoimmune disorder in which the
immune system attacks the spinal cord causing inflammation that
damages the cells that control sensory and movement of the
body.
After staying in the hospital for a couple of months, I
went to rehabilitation where I learned how to do everything
from a wheelchair, all the while having dreams of my feet
imprinting in the sand.
Today I am a 23-year-old woman who has learned to adapt to
a life in a wheelchair and in a paralyzed body. Even though I
live life to the fullest and look as though I am just sitting
down in a wheelchair, I don't have to always worry about
pressure sores from constant sitting. I worry about my
osteoporosis advancing in my bones from not standing and
bearing weight, which led to a fracture of my left femur. I
worry about my scoliosis getting worse, a curvature of the
spine common in people with spinal cord injuries. I have
bladder and bowel complications and advancing nerve pain. But I
am just one out of millions of Americans living with various
diseases and conditions that no matter how hard we try affect
how we live our lives.
The first time hope actually meant something me to and
became sort of my religion was when I saw what human embryonic
stem cells can do. A year after I became paralyzed, my doctor
and stem cell scientist, Doug Kerr, who was at Johns Hopkins at
the time, showed me a mouse that was once paralyzed and now can
bear its weight and take steps. At that moment, I realized that
this is science I could not ignore, and it gave me a feeling of
hope I wanted to fight for, which brings me to another point.
It is frustrating to hear critics of this research say this
is a path we cannot go down and adult stem cells hold just as
much promise as embryonic stem cells do. Science is the pursuit
of discovery and possibility. We should explore every
opportunity and not count anything out because I cannot wait.
And I know millions of Americans now and in the future cannot
wait.
In Christopher Reeve's testimony in 2000, he said, ``No
obstacle should stand in the way of responsible investigation
of their possibilities.'' I am here today to remove yet another
obstacle in the path of this research, this answer, this hope.
The political debate over this research is forcing many of
our brilliant scientists to think twice about whether they
should stay in this field. I know how dedicated and passionate
they are about helping all of us find answers to our pain and
suffering. If we keep dragging this debate back here to
Washington, in Congress, and in the courts, more and more
scientists will have no choice but to either find a different
research avenue or move to another country where they can
pursue the promise that embryonic stem cells possess. Once and
for all, I urge Congress to pass unambiguous legislation that
allows this research to move forward.
PREPARED STATEMENT
I grew up around racetracks, and my family has won the
Indianapolis 500 a total of nine times. The goal of every
driver is to pass under the black and white checkered flag
first. The meaning of the checkered flag is winning. Right now,
I can see the flag waiting for me to go by, but with this
current court ruling, I feel that I have been driving under a
long, yellow caution flag. Today I came here to say that this
research is real, promising, and hopeful to me and to others as
we want so much to take that checkered flag and win our battles
over diseases that constantly challenge our quality of life.
Thank you very much.
Senator Harkin. Thank you, Ms. Unser.
[The statement follows:]
Prepared Statement of Cody Unser
Thank you Chairman Harkin for allowing me to testify and use my
voice on behalf of millions of Americans living with debilitating
diseases. I feel very honored and to be honest, frustrated as to why we
are here today.
Ten years ago, my hero, my superman, Christopher Reeve sat in his
power wheelchair and using every breath he took thanks to a machine,
testified to Congress with the hope that embryonic stem cell research
would be federally funded. Today, in 2010, we are still fighting for
this promising and hopeful research to continue. Embryonic stem cells
are science based on hope. Hope for improving the quality of life of
millions of Americans by providing better treatment and eventually
cures.
My journey began 11 years ago. I was a healthy 12-year-old kid who
was very active and had big dreams. Everything changed on February 5,
1999. I can't recall how it felt to put my feet on the floor, how I got
dressed that morning or what I had for breakfast, but what I do
remember is that in a manner of 20 minutes my body became paralyzed and
my life drastically changed. I was playing basketball at school and
suddenly couldn't catch my breath and my head started bounding with
sharp pain. The school I was attending called the ambulance and while
laying down in the locker room my left leg became numb and tingly. I
picked it up, put it back down and I couldn't feel the floor. I was
scared out of my mind, but I thought that whatever was wrong the
doctors could fix. Transverse Myelitis is an autoimmune disorder in
which the immune system attacks the spinal cord causing inflammation
that damages the cells that control sensory and movement of the body.
After staying in the hospital for a couple of months I went to
rehabilitation where I learned how to do everything from a wheelchair
all the while having dreams of my feet imprinting in the sand.
Today I am 23-year-old woman who has learned to adapt to a life in
a wheelchair and in a paralyzed body. Even though I live life to the
fullest and look as though I am just sitting down in a wheelchair, I
have to always worry about pressure sores from constant sitting, I
worry about my osteoporosis advancing in my bones from not standing and
bearing weight which led to a fracture of my left femur. I worry about
my scoliosis getting worse, a curvature of the spine common in people
with spinal cord injuries. I have bladder and bowel complications and
advancing nerve pain. But I am just one out of millions of Americans
living with various diseases and conditions that no matter how hard we
try affect how we live our lives.
The first time Hope actually meant something to me and became sort
of my religion was when I saw what human embryonic stem cells can do. A
year after I became paralyzed, my doctor and stem cell scientist, Doug
Kerr who was at Johns Hopkins at the time, showed me a mouse that was
once paralyzed and now can bear its weight and take steps. At that
moment, I realized that this is science I couldn't ignore and it gave
me a feeling of hope I wanted to fight for. Which brings me to another
point. It's frustrating to hear critics of this research say this is a
path we can't go down and adult stem cells hold just as much promise as
embryonic stem cells do. Science is the pursuit of discovery and
possibility. We should explore every opportunity and not count anything
out because I can't wait. And I know millions of Americans now and in
the future can't wait. In Christopher Reeve's testimony in 2000 he
said, ``No obstacle should stand in the way of responsible
investigation of their possibilities''. I am here today to remove yet
another obstacle in the path of this research, this answer, this hope.
The political debate over this research is forcing many of our
brilliant scientists to think twice about whether they should stay in
this field. I know how dedicated and passionate they are about helping
all of us find answers to our pain and suffering. If we keep dragging
this debate back here to Washington, in Congress and in the courts,
more and more scientists will have no choice, but to either find a
different research avenue or move to another country where they can
pursue the promise that embryonic stem cells possess. Once and for all
I urge Congress to pass unambiguous legislation that allows this
research to move forward.
I grew up around racetracks and my family has won the Indianapolis
500 a total of nine times. The goal of every driver is to pass under
the black and white checkered flag first. The meaning of the checkered
flag is winning. Right now, I can see that flag waving for me to go by.
But with this current court ruling I feel that I have been driving
under a long yellow caution flag. Today, I came here to say that this
research is real, promising and hopeful to me and to others as we want
so much to take that checkered flag and win our battles over diseases
that constantly challenge our quality of life.
Thank you very much.
Senator Harkin. We now have two more votes, which I did not
anticipate. I will try to get in a few questions. How much time
do we have left? Eight minutes left?
A couple of things. Dr. Morrison, in your statement, you
alluded to claims made by some that adult stem cell research is
more promising than embryonic stem cells because adult stem
cells are already used to treat disease. We just heard a lot
about that from Dr. Peduzzi Nelson. Could you expand on that?
Should we be disappointed that embryonic stem cells have not
yet yielded a cure? And how about all these pictures and things
we just saw of people that have been cured by adult stem cells?
Dr. Morrison. These arguments that you hear about focusing
on adult stem cell research because they already treat people
are meaningless arguments because human embryonic stem cells
were first created in 1998. We have only had 12 years in which
to work on them, whereas the adult stem cell therapies that are
used clinically are related to bone marrow transplantation
which was started in the 1950s. So we have had decades of work
on adult stem cell therapies.
Now, let me tell a very quick story. The first attempt at
bone marrow transplantation between an unrelated donor and
recipient was in 1955 by Donnall Thomas and his team. All the
patients died. He went back to the laboratory to try to figure
out why it was that he could not just randomly transplant bone
marrow cells from one donor into another recipient and learned
that you had to match the immune systems of the donor and the
recipient so they did not attack each other.
The first successful transplant from an unrelated donor and
recipient was 1969, 14 years later.
So if we applied this criterion of abandoning any form of
research that does not lead to cures within 10 or 12 years, as
has been suggested by opponents of embryonic stem cell
research, then none of these adult stem cell therapies would
exist today and, frankly, most of the medicines that we benefit
from would never have been possible to develop.
Senator Harkin. Dr. Daley, one line in your testimony. You
said iPS cells and embryonic stem cells are different in
important ways. I understand you have an NIH grant to examine
this very issue that could be endangered, I understand, if
Judge Lamberth's injunction were upheld.
Again, tell me why this research is so important. What are
the future discoveries that could be spurred by isolating the
differences between these two types of cells?
Dr. Daley. Yes. It is a major question to compare this new
and very exciting and very powerful type of iPS cell against
the embryonic stem cell, and we have one such grant. I am
losing a lot of sleep over the future of that grant because
when the injunction was in place, that grant was threatened. It
was going to be pulled. It was not going to be renewed, and
very promising projects that involve seven different
institutions, the University of Miami, Boston University, Johns
Hopkins, as well as Harvard Medical School, were all at risk.
What our research has shown, our early research, primarily
in mice and now also in humans, is that whereas our goal is to
make iPS cells as close as possible to embryonic stem cells,
despite our best efforts to date, there are still some
differences. And understanding those differences is essential
to understanding how those cells will behave in all of our
research projects and ultimately for therapy.
What we found is that after we turned the skin cells or the
blood cells back to their embryonic state, they remember where
they came from. Now, that can be an advantage. For us we are
interested in treating blood diseases, and so we are migrating
our work to work with iPS cells that are derived from the
blood. But if you are interested in treating Hirschsprung
disease or in treating liver disease, this fact that that
memory exists may actually thwart your research.
So fundamentally we are still so ignorant about how these
new types of stem cells are going to function. We continue to
depend on human embryonic stem cells.
AUTOLOGOUS STEM CELL TREATMENT
Senator Harkin. Thank you very much.
I have got some more. There are two more votes. I cannot
hold you here any longer.
Dr. Collins, Dr. Peduzzi's presentation see these people
that have been cured--I have had people like that in my own
office who have come in who have had autologous stem cell
treatment in another country, and they come in and openly
testified that whereas they could not walk, now they could a
little bit. One person also had heart problems. What do I make
of all this?
Dr. Collins. So Dr. Peduzzi Nelson's examples are, in fact,
exciting to see the potential that is here.
Rob Califf who runs the clinical center at Duke once said
something that I thought was kind of important, though, in all
of this, that God gave us two gifts for understanding whether a
treatment works or not: blinding and randomization. And if you
have not applied those standards to an intervention, then you
have to be skeptical because things happen that have nothing to
do with the intervention. So the studies----
Senator Harkin. What did you say again, Dr. Collins?
Dr. Collins. Blinding, that is, the patients and the
investigators cannot know whether that individual received the
new treatment or some other placebo approach. And
randomization, that is, patients get randomized to one or the
other arm so that you do not have a bias in the outcome just
based on their not being well matched.
For all of us involved in medical research, until an effort
has been put through that particular very stringent test, then
one has to be a little concerned about whether what has
happened is going to be generalizable. And that is what we
want. We want things that you know will work for lots of
people.
The exciting research reported by Dr. Peduzzi Nelson for
the most part has not yet reached that standard in terms of the
spinal cords results that she talks about with these olfactory
mucosal cells, although I think it is very exciting to see how
that is. In fact, I understand there is an Australian study
that has had difficulty replicating that. I am not, by this,
saying that we should not be supporting that research. It is
very exciting. We should be. But let us be clear about what we
consider to be proof of success. Whether we are talking about
human embryonic stem cells or iPS cells or adult stem cells, we
have to be rigorous in our standards about when we are clear
that we have established something confidently.
Dr. Peduzzi Nelson. If I might make a comment.
Senator Harkin. Dr. Peduzzi, I will give you a minute
because I have got to go vote. I am sorry. Go ahead.
Dr. Peduzzi Nelson. Just 1 minute. I would like to say that
Dr. Collins is correct. And what I am saying is that we need
the funds. We need funding from NIH and the Department of
Defense, to bring these clinical trials to the next phase where
there is blinding and there is randomization.
I would like to make the second point. There is some
confusion with the study in Australia. They in no way
replicated the work in Portugal. They were using a different
cell type.
But beyond the fact about blinding and randomization, we do
need that. In the case of the Portugal trial, there is a
problem in that this is a surgical technique. They are actually
putting the cells and tissue into the spinal cord. So you
cannot go to the standard of having patients have a sham
surgery. So that is part of the difficulty in verifying the
technique.
But all of these other clinical trials that I presented
need to be replicated in the United States and they need to be
brought on to the clinical trial where you do blinding of the
patients, meaning that the people doing the investigation do
not know if they received the treatment or not and the patient
does not know that. So we need to move in that direction, and
it is terribly expensive.
Senator Harkin. Do you think that funding for embryonic
stem cell research should be prohibited?
Dr. Peduzzi Nelson. This gets to--I am here as a scientist
and not here giving a personal opinion. As a scientist, what I
came here to say is that in this country and other countries,
we have seen some results that are, frankly, amazing, that are
published in major journals that are clinical trials, and we
need the funding for adult stem cells so they can become
standard of care. It does not do anyone any good to treat 5 or
10 patients.
ADDITIONAL COMMITTEE QUESTIONS
Senator Harkin. I am sorry.
Ms. Unser, again, I thank you very much for being here
today. You are a very courageous young woman and thank you for
picking up Christopher Reeve's mantel and moving ahead with it.
I compliment you very much on that.
I thank our whole panel. Thank you for being here. I am
sorry. I could stay here and talk about this for another hour.
I have got other things that I want to ask. I may submit
questions to you in writing, and I would appreciate your
responses to those.
Dr. Collins, again, thank you very much.
[The following questions were not asked at the hearing, but
were submitted to the Department for response subsequent to the
hearing:]
Questions Submitted by Senator Thad Cochran
SCIENTIFIC HURDLES
Question. In your testimony you said ``. . . our best window into
human development is using human embryonic stem cells.'' In July, the
Food and Drug Administration (FDA) authorized the first test--in
humans--of an embryonic stem cell therapy. When these cells were
tested, partially paralyzed animals walked. Dr. Collins, what is the
most significant hurdle in translating current stem cell research into
treatments like the one recently approved by the FDA?
Answer. To use human embryonic stem cells (hESCs) for cell
replacement and/or repair we must develop procedures that consistently
produce a stem cell product that is appropriate for the specific use
and safe for use in humans. Each particular disease or condition to be
treated is likely to require a different cell therapy product. In some
cases, scientists know the cell type required and the steps required
for it to be produced. In others, they know the cell type required but
not how to produce it and in yet others, investigators may not be sure
what cell type would be most appropriate. Once the cell type has been
identified and a protocol developed, scientists need to demonstrate the
ability to produce enough of the desired cells consistently to allow
comprehensive preclinical safety testing in animals, and support
initiation of an early phase clinical trial in humans under FDA
oversight. Significant hurdles during this stage of the process include
manufacturing product of sufficient purity, tracking the cells inside
the animal's body, and confirming that the cells integrate functionally
into the target tissue. The timeframe for developing a stem cell
therapeutic could easily be 10 years. For the few private companies
making progress in the field of stem cell biology, such as Geron and
ViaCyte, private sector funding has been consistent over a long period
of time, while public funding has been unpredictable. If stem cell
therapy is left to the private sector alone, development will likely be
more restricted in breadth, access to research tools or results could
be limited due to proprietary constraints, and innovative research may
not be undertaken, thus hampering progress and threatening United
States predominance in the field.
Question. In your testimony, you said that human embryonic stem
cells are a better model for how humans will respond to drug treatment
than the current method using animal models. Can you expand upon this
and provide a few examples?
Answer. In the past, testing a drug or intervention on an animal
model has been the best test that could be done before actually testing
a drug on human beings in a clinical trial. In using an animal model,
scientists are making an assumption that the human body is likely to
respond to the drug or intervention being tested in a manner similar to
that of the animal model's body, because humans and other animals are
so similar in genetic makeup. However, scientists may now be one step
closer to observing how the human body will respond to a therapy: we
can use hESCs to generate the tissue of interest (heart, brain, skin,
etc.) and then test the drug or intervention on those human cells for
safety and effectiveness.
For example, in the area of diabetes, scientists have identified
numerous therapies that ``cure'' Type 1 diabetes in mice. Many of those
treatments, however, that seemed so promising in the mouse have not
proven to be effective in treating human diabetes. So, although animal
models such as mice are still useful, they cannot tell us exactly how
humans will respond. Scientists are making significant progress in
learning how to coax hESCs into becoming mature human beta cells--the
cells that produce insulin. They hope that these cells will be more
useful tools to test potential diabetes drugs or other interventions
and better predict how the human body will respond.
In the area of heart disease, hESCs may also prove to be an
invaluable tool. Although early stage clinical trials of drugs designed
to improve heart function sometimes report positive results, the later
stages are frequently halted due to unanticipated and negative side
effects of the tested drug. Many of the drugs end up harming the very
cells they were meant to help--the human heart cells, or
cardiomyocytes. Scientists have now produced clinical grade
cardiomyocytes from hESCs, and they hope that testing promising drugs
on these cells prior to beginning clinical trials will speed safe and
useful heart disease drugs to the many who need them.
FEDERAL FUNDING
Question. If Federal funding is no longer available to support hESC
research, would private or State funding be able to maintain the
current pace of research?
Answer. No. It would be extremely difficult for State or private
funding in the United States to maintain the current pace of hESCs if
Federal funds were no longer available.
Currently, less than a dozen States have implemented funding
programs for hESC research and the amount of research funding varies
from State to State. When State research funds are available, the funds
are restricted to scientists who conduct research within those States.
However, scientists from all States are eligible to apply to the
National Institutes of Health (NIH) for research funding and NIH awards
grants based on the scientific merit of the research proposed. In
fiscal year 2009, NIH made hESC research awards to institutions in 22
different States.
In addition, although there is no hESC policy in the United States
that applies to both the public and private sectors, the NIH Guidelines
for Human Stem Cell Research provide ethical standards for the States
to follow if they choose.
Without the central direction and coordinated research approach
that the Federal Government can provide, many are concerned that the
States' actions will result in duplication of research efforts among
the States, variation in the level of ethics oversight, and ultimate
loss of U.S. pre-eminence in basic hESC research, the foundation of
translational and clinical hESC research.
Long-term investment in basic research is necessary before
scientific findings can be translated into clinical applications. For
example, research is needed to understand the basic biology of hESCs
before scientists can determine how hESCs can be coaxed into a
particular cell type before stem cells can be used for drug testing or
use in regenerative medicine. NIH is more likely to support these
fundamental studies. Basic research must produce evidence of clinical
relevance and demonstrate a potential market before the private sector
will take up the research.
INTERNATIONAL COMPETITIVENESS
Question. Medical research is projected to be one of the chief
sectors for job growth over the next decade. What is the most
significant hurdle for American scientists to remain competitive in the
international stem cell arena?
Answer. The most significant hurdle for American scientists to
remain competitive in the international stem cell arena is the
uncertainty of Federal funding for hESCs. In contrast, there is strong
government support and investment in hESC in countries such as
Singapore, India, China, and the United Kingdom. A 2008 study ranked
the United States as a low performer in hESC research as compared to
its leadership in other areas of emerging, but noncontroversial,
biomedical research.\1\ Notably, the top four high-performing countries
in hESC-related research (United Kingdom, Israel, China, and Singapore)
all have supportive government policies for this field. The uncertainty
in Federal funding for hESC research discourages established
investigators from pursuing promising leads since they cannot count on
stable funding for their best projects. Outstanding young scientists
are reluctant to focus their efforts on promising hESC research when
they may not be able to continue because of changes in funding policy.
---------------------------------------------------------------------------
\1\ Levine, A.D. ``Identifying Under- and Overperforming Countries
in Research Related to Human Embryonic Stem Cells'' Cell Stem Cell 2,
June 2008, pp. 521-524.
---------------------------------------------------------------------------
______
Question Submitted by Senator Patty Murray
RESEARCH FUNDING
Question. In your testimony, you mentioned that the National
Institutes of Health (NIH) has invested more than $500 million in human
embryonic stem cell (hESC) research since 1998. You also mentioned that
stopping Federal investment of this research mid-stream would result in
wasting the funds that have been put in accounts or already drawn down.
You stated this wasted amount will amount to $270 million. This
inconsistent policy of Federal support has effects on research budgets
and planning. As a researcher, have you seen how this policy has
affected budgets for promising research? Could you expand a little bit
on how looking for other types of funding when Federal support stops
and starts affects the continuation of research?
Answer. Speaking as both NIH Director and a researcher with my own
laboratory, even a temporary suspension of funds can jeopardize ongoing
research projects. When a laboratory experiment or clinical study is
interrupted, it cannot be easily restarted. Such experiments may
involve biological materials such as cell lines growing in lab
incubators that must be managed daily to encourage growth and prevent
contamination. Valuable laboratory animals serving as models of a wide
range of human diseases and disorders that are being used to test new
therapies could be lost due to the lack of funds to pay personnel to
care for them. Once critical research tools and reagents--including
unique materials that have taken years to develop--have been lost for
lack of funding, it may take months or years to recreate them, if that
is even possible. In clinical research projects, it can be very
difficult to maintain the willingness of participants to stay involved
with research. In cases where clinical interventions are being tested,
this could pose severe ethical concerns about benefits and risks to
those who have received only part of the scheduled protocol. In
addition, laboratory personnel whose jobs depend on grant funds may be
let go and the best investigators, including promising young
investigators, may abandon that particular line of research or possibly
move to other countries that have more predictable support for hESC
research.
CONCLUSION OF HEARING
Senator Harkin. Thank you all for being here. I am sorry I
have to run.
[Whereupon, at 12:17 p.m., Thursday, September 16, the
hearing was concluded, and the subcommittee was recessed, to
reconvene subject to the call of the Chair.]
MATERIAL SUBMITTED SUBSEQUENT TO THE HEARING
[Clerk's Note.--The following testimonies were received by
the Subcommittee on Labor, Health and Human Services, and
Education, and Related Agencies for inclusion in the record.
Prepared Statement of the American Association for Cancer Research
The American Association for Cancer Research (AACR), the world's
oldest and largest professional organization dedicated to advancing
cancer research, represents more than 32,000 cancer researchers,
physician-scientists, other healthcare professionals, and survivors and
patient advocates. On behalf of AACR, I thank you, Chairman Harkin and
members of the Senate Appropriations Subcommittee on Labor, Health and
Human Services, and Education, and Related Agencies, for holding this
important hearing on the future and promise of human embryonic stem
cell research. The AACR appreciates the opportunity to share its views
on this issue.
There is vast potential for stem cell research to improve the
prevention, diagnosis, and treatment of cancer and many other diseases.
Human embryonic stem cell research, in particular, may lead to new
biological insights that offer previously unknown avenues for the
development of promising new therapies for cancer patients. As stated
in our 2005 policy statement on stem cell research,\1\ the AACR
believes that reasonable, ethical exploration of the full spectrum of
stem cell biology is a crucial component of scientific discovery.
---------------------------------------------------------------------------
\1\ American Association for Cancer Research. Responsible
Exploration of the Full Spectrum of Stem Cell Biology is Essential to
the Advancement of Cancer Research. Position Statement, 2005. http://
www.aacr.org/home/public-media/aacr-press-releases/press-releases-
2005.aspx?d=482.
---------------------------------------------------------------------------
THE COURT INJUNCTION IS A SETBACK FOR SCIENTIFIC DISCOVERY AND CANCER
RESEARCH
Scientists who were recently given new opportunities under
President Obama's Executive order \2\ to pursue important research
questions using human embryonic stem cell lines could now be stopped in
their tracks. The recent decision by the Federal District Court of the
District of Columbia to block Federal funding for human embryonic stem
cell research underscored the instability faced by scientists working
in this promising field. The injunction created mayhem for scientists,
who in the blink of an eye became unsure whether they could legally
continue their experiments funded by the National Institutes of Health
(NIH). A whole cadre of young scientists interested in pursuing this
area of science may be discouraged from doing so due to concerns about
funding stability. The AACR is deeply concerned that the lack of
clarity on Federal funding for human embryonic stem cell research will
significantly affect the ability of the United States to be a leader in
this cutting-edge field of science that has real potential to save
lives. United States scientists already face a distinct disadvantage in
this field compared to their colleagues in countries such as Great
Britain and Australia with more progressive, yet still ethically
responsible, policies. While the injunction temporarily was lifted,
great uncertainty remains as the case goes to the appellate court.
---------------------------------------------------------------------------
\2\ On March 9, 2009, President Barack H. Obama issued Executive
Order 13505 Removing Barriers to Responsible Scientific Research
Involving Human Stem Cells.
---------------------------------------------------------------------------
HUMAN EMBRYONIC STEM CELL RESEARCH HOLDS MUCH PROMISE FOR CANCER
PATIENTS
Stem cell research is part of a multi-faceted approach to
understanding the biology of cancer and developing new ways to combat
the 200 diseases collectively called ``cancer.'' Potentially paradigm-
shifting research may be developed from embryonic stem cell research,
as scientists are just now learning what potential these stem cells
hold and how they differ from the less-controversial adult stem cells.
For example, recent scientific discoveries have shown that human
cancer cells often display features that are reminiscent of human
embryonic stem cells and that the more a cancer cell resembles an
embryonic stem cell, the more aggressive its behavior. Indeed, it is
only now being appreciated that the initiation and progression of many,
if not all human cancers, involves deregulation of the very same genes
and pathways that are necessary and responsible for normal human
embryonic development. Inappropriate activation of these pathways in an
adult cell can overtake its development and drive creation of a tumor.
Early studies in the laboratories of numerous cancer researchers
are showing that if these genetic and epigenetic errors are corrected,
the growth of the cancer can be slowed or even reversed. However,
successful translation of these exciting laboratory discoveries into
advances for patient care requires that we better understand the
differences between normal embryonic stem cell and cancer biology. To
achieve this, it is absolutely imperative that this fundamental
research, which has already led to so many significant discoveries, be
allowed to continue. This research de facto depends on laboratory-based
investigations of human embryonic stem cells.
Another important advancement in cancer research has been the
discovery that certain tumors arise as a consequence of genetic
mutations in normal adult stem cells. For example, leukemia can arise
when mutations occur in normal hematopoietic (blood) stem cells, and
brain tumors can arise as a consequence of mutations in normal neural
stem cells. The ability to isolate normal hematopoietic stem cells from
bone marrow has fueled discovery into the origins of leukemia and is
leading to the development of novel therapies to target leukemia stem
cells. However, because of the relative rarity and inaccessibility of
other adult stem cells, very little is yet known about their normal
biology or how they morph into cancer cells. Cancer researchers are
harnessing the pluripotency and regenerative power of embryonic stem
cells to generate these rare adult stem cells in the laboratory.
As a renewable source of neural, neural crest, pancreatic, liver,
and other tissue-specific stem cells, embryonic stem cells are--for the
first time--providing cancer researchers with the tools to study
differences between normal adult stem cells and cancer stem cells.
Already these studies are generating novel insights into tumor biology
and identifying potential therapeutic targets that could be exploited
to selectively kill cancerous stem cells.
The benefits of this research are applicable especially to the
pediatric population. Given that fully two-thirds of childhood cancer
survivors are afflicted with long-term side effects from cancer
treatments that negatively impact their health and well being, it is
imperative that we strive to develop new therapies for pediatric
cancers that spare normal stem cells and developing tissues. The
promise of human embryonic stem cells as tools for scientific discovery
provides hope for these children and for all patients who are afflicted
with brain tumors, bone and soft tissue sarcomas, neuroblastoma,
malignant melanoma, pancreatic, liver, and other solid tumors that all
too frequently resist current therapies.
AACR SUPPORTS SOUND, ETHICAL AND RESPONSIBLE STEM CELL RESEARCH
POLICIES
The AACR believes that human embryonic stem cell research must be
conducted in accordance with policies that are sound, ethical, and
responsible. As with any scientific investigation, explorations of stem
cell biology must be pursued in strict accordance with such policies to
safeguard the welfare of research donors and recipients. Individuals
donating biological materials for research--including somatic cells,
gametes and embryos--need to give their fully informed and voluntary
consent through a mechanism uncompromised by financial incentive.
The NIH has exerted significant effort to ensure that this
promising research, like all NIH research, is conducted in a manner
consistent with established ethical principles. After a thorough and
transparent process involving extensive public input, the NIH put forth
guidelines last July that stipulate the assurances and supporting
documentation that must accompany requests for NIH funding for research
using human embryonic stem cells. The guidelines also expressly
prohibit funding for research projects using lines derived for the
purpose of research through processes such as somatic cell nuclear
transfer, in vitro fertilization or parthenogenesis. Neither Obama's
Executive order nor the NIH guidelines permit Federal funding to be
used for the generation of new stem cell lines.
In considering its support for research utilizing human embryonic
stem cells, the AACR recognizes and shares the universal sentiment that
the human embryo deserves respect. Research involving human embryonic
stem cells must serve important research aims that cannot be reached by
other means. Moreover, we agree with the internationally accepted 14-
day limit on the developmental age of blastocysts from which the
embryonic stem cells are derived.
Although research using human embryonic stem cells raises many
important ethical considerations, the majority of Americans believe
that the potential for research to yield significant advances in
patient care warrants responsible conduct of research. A 2008 Time
magazine poll showed that nearly three-quarters of Americans support
embryonic stem cell research using cells derived from embryos that will
be discarded following in vitro fertilization procedures.\3\ Enforcing
strict guidelines with appropriate oversight will ensure that such
research is conducted according to the highest ethical standards.
---------------------------------------------------------------------------
\3\ SBIR Research poll for Time magazine. June 2008. http://
www.pollingreport.com/science.htm. Accessed September 8, 2010.
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CONCLUSION
The AACR believes that stem cell research can be conducted in a
manner consistent with established ethical principles, and strongly
supports responsible explorations of the full spectrum of stem cell
biology, including the use of human embryonic stem cells, for
meritorious scientific research and therapy development.
The AACR has been moving cancer research forward since its founding
in 1907. The AACR and its more than 32,000 members worldwide strive
tirelessly to carry out its important mission to prevent and cure
cancer through research, education, and communication. Responsible
embryonic stem cell research holds tremendous promise to deliver new
therapies to patients suffering from cancer, as well as many other
diseases such as heart disease, Parkinson's, diabetes, Alzheimer's,
HIV/AIDS, and spinal paralysis.
______
Prepared Statement of the Americans for Cures Foundation
Honorable Senators Tom Harkin and Thad Cochran, members: Thank you
for this opportunity to provide testimony on a subject which affects
100 million Americans with a chronic (incurable) disease or
disability--and everybody who pays the medical bills.
The costs are staggering: last year, chronic illness cost America
$1.65 trillion, more than all Federal income taxes ($1.2 trillion)
combined. The suffering is incalculable.
These are not empty statistics, but members of your family and
mine: people like my son.
On September 10, 1994, Roman Reed was playing college football. At
middle linebacker he was having a great game: 11 solo tackles, a diving
one-hand interception, a forced and recovered fumble.
And then, the accident. There was a hideous sound, like an axe
handle breaking on a rock. In an instant our son was paralyzed from the
shoulders down. He was 19.
The doctors gave us no hope.
``He will never walk again, nor close his fingers; almost certainly
no children'', they said.
We would not accept that diagnosis then, and we do not accept it
now. We worked to find a cure.
With the leadership of Fremont Assemblyman John Dutra, we passed a
California law, Assembly Bill 750, the Roman Reed Spinal Cord Injury
Research Act of 1999.
On March 1, 2002, I held in my hands a rat which had been
paralyzed, but which walked again, thanks to embryonic stem cells--as
my son watched from his wheelchair.
This was the famous experiment to re-insulate damaged nerves in the
spine. Geron is taking it to the world's first human trials of
embryonic stem cells, recently approved by the Food and Drug
Administration (FDA). Ten newly paralyzed young men or women will be
offered a chance my son did not: to maybe get better, through embryonic
stem cell research.
``Roman's law'' funded the first use of the Presidentially approved
embryonic stem cell lines. And, importantly, the Federal Government
backed us up. For our total expenditure of $14 million over 9 years, we
brought in an additional $60 million in follow-up grants and matching
funds from the National Institutes of Health (NIH), new jobs and
revenue. But it was not enough.
For a cure to come, not only for paralysis, but also the dozens of
incurable diseases afflicting so many, the entire field of regenerative
medicine had to advance.
In 1942, research connected with the medical aspects of radiation
sickness from the atomic bomb revealed that bone marrow transplants had
healing properties. That was the beginning of adult stem cell research,
which has proved extremely useful in the treatment of forms of cancer
and blood disease.
But it is not the exclusive answer to all chronic illness and
injury.
Embryonic stem cells which build every portion of the body are also
important.
The difference between adult and embryonic stem cells is like the
difference between gift certificates and cash money--one can only be
spent in certain places, the other is acceptable everywhere.
For example, adult stem cells heal surface wounds slowly, leaving a
scar. Embryonic stem cells build the entire human body. The difference
is power is extraordinary.
For the field of regenerative medicine to advance, both types of
cells are needed. Each is different and has different powers and
purposes.
But there are subtle dangers to be aware of with adult stem cells.
They cannot always do what embryonic stem cells can. Sometimes adult
cells which have been experimentally turned into useful cells revert to
their original adult stem cell state. One attempt to turn adult stem
cells into nerve cells did not last, and after a few days, the rats
which had the cells implanted developed excruciating pain, so they
gnawed off their paws. (A replication of this study was done by Dr.
Candace Floyd, UC Davis.)
An approach I regard as a failure is the attempt to use Olfactory
Epithelial Glia (OEGs) to restore spinal cord function, basically
reaching a scalpel up into the nose and scraping off part of the brain,
which is then spread like jelly on the injured spine. I have spoken
with a recipient of that treatment who described (after an expenditure
of approximately $40,000) the essential failure of it: the paralyzed
person regained a patch of skin sensation on his elbow, so that he
could feel his sleeve go on, when they dressed him in the morning.
Much has been said about ``adult stem cell treatments for 70
diseases'', but this is misleading at best. Prescribing aspirin for
cancer may be a treatment, but it is not a cure.
The ancient scientist Galen spread pigeon dung on the spines of
paralyzed gladiators. It was a treatment, but hardly a successful one.
The idea of adult stem cells being ready to be the sole standard of
treatment is not only unwise but cruel, imposing something unreliable
in place of the possibility of actual cure.
California's Bob Klein began an initiative, Proposition 71, the
Stem Cells for Research and Cures Act. I was proud to serve on the
board of directors of that successful effort.
But even when 7 million voters approved the $3 billion stem cell
program, lawsuits were hurled against us: frivolous in their grounds,
but devastating in their consequences.
For almost 2 years the full program was held up. Research delayed
is research denied. Who knows what might have been discovered during
that time, if we had our program fully operational?
But we prevailed, and today the California Institute for
Regenerative Medicine (CIRM) is the pride of our State and a friend to
all the world.
Recently, four major grants, $20 million each, were awarded by the
CIRM for embryonic stem cell research: Lou Gehrig's disease, stroke,
juvenile diabetes, and age-related blindness were chosen. Each is an
attempt to do the impossible with the invisible: to try and heal a
malady incurable since the dawn of time.
Cures the CIRM develops will benefit everyone; not only the
individual families whose suffering will end, but also the economies of
every nation, struggling to pay mountains of medical debt. All will
benefit.
But we need the Federal Government to help with the enormous costs
which wait beyond initial research: the ``valley of death'' which faces
all new medical discoveries: the costs of turning theory into therapy,
all the way from bench to bedside, may approach $1 billion.
California's program has a budget of approximately $300 million a year:
we can't do it alone.
March 9, 2009, a day of joy. Roman, Gloria and I were in the room
when President Barack Obama reversed the Bush restrictions. Now, at
last, the Federal Government would take its rightful place, leading in
the quest for cure.
But another obstacle arose. The case of Sherley v. Sebelius may
shut down Federal funding of the research so many patients and families
have worked to advance.
The argument is often made by ideological opponents that embryonic
stem cell research is a form of abortion.
This is false. How can there be an abortion, when there is no baby?
There is no pregnancy in embryonic stem cell research. Nothing is
placed in the womb. It is biologically impossible for an unemplanted
blastocyst to become a child. It is living tissue, like a wiggling
sperm, but not a life. It cannot possibly become a child without the
nurturing protection of a mother's womb. No mother, no baby: this is
unarguable fact.
Congress had a full and vigorous debate on Federal funding for the
research: and approved it twice. The Stem Cell Research Enhancement
Acts of 2005 and 2007 passed both houses with strong majorities.
President Bush exercised his prerogative and vetoed both bills, but the
will of Congress was crystal clear.
The Senate, the House of Representatives, and the President of the
United States support Federal funding of embryonic stem cell research.
If research funding is blocked for ideological reasons, we abandon
a principle: that every American family deserves the best medical
treatment science can provide.
Denying cure condemns 2 million paralyzed Americans like my
paralyzed friend Karen Miner to a life sentenced incarcerated in a
chair; it diminishes hope for those who suffer cancer and leukemia,
which killed my mother and my sister Patty; and it slows the growth of
jobs in America's shining new industry: biomedicine. Nine years ago,
September 5, 2001, I provided testimony for Senator Edward Kennedy's
similar hearings on scientific freedom for stem cell research. I
conveyed my son Roman Reed's request, asking that the Senate:
``Take a stand: take a stand in favor of medical research; take a
stand-so one day everybody can.''
Roman and his wife Terri, and their three children, Roman Jr.,
Jason, and Katie--send that message again.
Finally, I would be remiss if I did not cite one of America's
greatest advocates.
The late Christopher Reeve sent a dictated letter to our family. It
said: ``One day, Roman and I will stand up from our wheelchairs, and
walk away from them forever.''
Cure did not come in time for the paralyzed Superman, but we still
believe in his great dream. Our champion has fallen, but the flame of
his faith still lights our way. He always said, we must ``go forward''.
And we will go forward: because America has picked up the torch.
______
Prepared Statement of the California Institute for Regenerative
Medicine
In 2004, 7 million Californians, accounting for 59 percent of the
electorate, approved Proposition 71, The Stem Cell Research and Cures
Initiative; creating the California Institute for Regenerative Medicine
(CIRM), the State stem cell institute. In the ensuing 5 years,
scientists and clinicians empowered by CIRM have made extraordinary
advances in medical research.
As the largest United States based funder of human embryonic stem
cell research during the Bush administration, CIRM has a unique
understanding of the importance of stable funding for therapies derived
from human embryonic stem cell research. At least four grants for
therapies derived from human embryonic stem cells are currently headed
towards human clinical trials, including: Type 1 Diabetes, Stroke,
Macular Degeneration (age-related vision impairment or blindness), and
Amyotrophic Lateral Sclerosis (ALS--Lou Gehrig's Disease).
NATIONAL INSTITUTES OF HEALTH (NIH) GRANTS FOR HUMAN EMBRYONIC STEM
CELL RESEARCH COVER CRITICAL WORK ON WHICH CIRM/CALIFORNIA RESEARCH IS
DEPENDENT
Although California-based embryonic researchers receive substantial
financial commitments from CIRM, the NIH's backing is crucial for many
of our grantees. If the Federal Government stopped funding embryonic
stem cell research, many of our grantees most promising work would be
in jeopardy. With 50 percent of our stem cell researchers responding,
more than 31 of our grantees that perform embryonic stem cell research
have indicated that they also received NIH funding covered by NIH
regulations. The reported total value of these grants is $45.5 million.
Virtually all reported there would be negative impact on their research
if NIH funds were cut.
More importantly, halting this research will have a devastating
impact on the future of the field and the United States' leadership
position in biomedical research. With a 50 percent response rate, 16 of
our grantees reported the need to eliminate or reduce postdoctoral
positions, if NIH funding is not permanently restored. America's best
and brightest scientists are unlikely to enter this promising field if
Federal funding is cut off or stagnant.
While we are thrilled California is among the worlds leaders in
biomedical research, California cannot drive the field alone. It is
imperative for the NIH, the leading funder of biomedical research in
the world, to fund this vitally important field. Collaboration between
scientists at different institutions around the world is imperative if
we are going to develop therapies and cures to fight some of today's
most debilitating diseases. The collaboration among many of these
scientists depends on U.S. scientists receiving NIH funds.
VALIDATING THE POTENTIAL FOR THERAPIES DERIVED FROM HUMAN EMBRYONIC
STEM CELLS
In October 2009, CIRM awarded $230 million for 14 unique
multidisciplinary Disease Team Research Awards. The goal of these
awards is to develop new medical therapies from stem cell research to
reduce the suffering from chronic disease and injuries to cure these
conditions, if possible. According to an international peer review
panel of 15 scientists (all from outside of California) the Disease
Team grants and loans, have all demonstrated ``compelling and
reproducible evidence'' that ``demonstrates that the proposed
therapeutic has disease- (or injury-) modifying activity. The project
is sufficiently mature, such that there is reasonable expectation that
an Investigational New Drug (IND) filing'' for a phase 1 human trial
``can be achieved within 4 years of the project start date.''
As previously stated, four of these projects utilize embryonic stem
cell research to treat some of today's most harmful conditions,
including: Type 1 Diabetes, stroke, macular degeneration, and
amyotrophic lateral sclerosis (ALS--Lou Gehrig's Disease).
TYPE 1 DIABETES
This public-private disease team partnership between Novocell Inc.
and the University of California San Francisco (UCSF) has developed
methods to make large-scale batches of replacement beta cells from
human embryonic stem cells (hESC). The team has demonstrated that these
hESC-derived beta cells cure experimental diabetes in mice and rats.
Additionally, they have devised strategies to reduce the risk that
recipients will see these implanted hESC-derived beta cells as foreign
cells and subsequently reject them. The team now plans to complete the
manufacturing, efficacy, safety testing required to generate the
necessary data for Food and Drug Administration approval to test in
phase 1 clinical trials.
STROKE
Led by renowned Stanford and University of California Los Angeles
(UCLA) researchers, this team has produced preliminary evidence on the
use of cells derived from human embryonic stem cells as a poststroke
treatment to improve recovery in the weeks and months following a
stroke. The team has developed a technique that to restrict the
potential of embryonic stem cells to neural stem cells that
differentiate only into cell types that are normally found in the
brain. When these neural stem cells are transplanted into the brains of
mice or rats 1 week after a stroke, the animals are able to regain
strength in their limbs. Based on these findings, the Stanford led team
proposes to further develop these neural stem cells into a clinical
development program for stroke in humans at the end of this grant
period.
MACULAR DEGENERATION (AGE-RELATED VISION IMPAIRMENT OR BLINDNESS)
The multidisciplinary team led by researchers at the University of
Southern California and the University of California--Santa Barbara
have produced preliminary evidence on the use of human embryonic stem
cells to replace dysfunctional or destroyed retinal pigment epithelial
cells to slow or reverse the disease. They plan to coax human embryonic
stem cells to differentiate into a monolayer of retinal pigment
epithelial cells that can be transplanted into the eye. The replacement
RPE cells will function normally to support and protect the light-
sensitive cells of the retina and prevent further degeneration and
vision loss.
ALS--LOU GEHRIG'S DISEASE
This San Diego based team (from the Salk Institute for Biological
Studies, University of California San Diego, and the Ludwig Institute
for Cancer Research) plans to protect surviving neurons in people
diagnosed with ALS from further degeneration. The strategy involves
targeting glial cells, which are neuroprotective cells that surround
and support neurons. A type of glial cell called an astrocyte is found
in both the brain and spinal cord and acts as a regulator of glutamate
surrounding motor neurons. The team intends to grow human embryonic
stem cell-derived astrocyte precursors that will be transplanted
directly into the spinal cord environment to prevent further
neurodegeneration caused by ALS. The work, which is based on mouse
experiments, should be effective in both familial and sporadic ALS.
ALZHEIMER'S DISEASE
Alzheimer's disease, the most common cause of dementia among the
elderly and the third-leading cause of death, presently afflicts more
than 5 million people in the United States, including more than 500,000
in California. University of California Irvine (UCI) received an early
translational grant from CIRM aimed at developing a development
candidate for treating Alzheimer's disease. Their proposed studies,
utilizes embryonic stem cells to develop a novel and promising strategy
for creating an effective therapeutic. Their preliminary studies
indicate that stem cell biology may provide a significantly more
effective therapy for the disease than any current pharmaceutical
products. These results, however are preliminary, and will require
years of additional research to confirm the potential.
We have a moral obligation as citizens of the United States to
support the dedicated scientists, clinicians, and patient advocate
organizations to pursue the best scientific approaches across the
scientific field of stem cell research, including human embryonic stem
cell research--to reduce the suffering of our families and friends and
families around the world.
______
Prepared Statement of the Student Society for Stem Cell Research
On behalf of the Student Society for Stem Cell Research (SSSCR),
our chapters across this great Nation, and our membership worldwide, we
urge Congress to act expeditiously to address recent events regarding
Federal funding of human embryonic stem cell research. The recent
preliminary injunction against human embryonic stem cell research in
Judge Lamberth's district court is deeply disturbing and threatens the
education and training of thousands of students. More specifically,
graduate students working on human embryonic stem cell projects
supported by the National Institutes of Health (NIH) are in danger of
having their financial support entirely cut off. Our constituency is
directly affected by the court's ruling. Many of us will not be able to
continue our biomedical programs if the injunction holds and Congress
fails to act. Simply stated, we will lose our means of financial
support and potentially our careers. The impact on the American people
will be devastating as our country risks losing scores of developing
scientists working on the most promising medical science in human
history.
On March 9, 2009, SSSCR and the more than 3,500 members of our
network were elated when President Obama issued Executive Order 13505,
entitled ``Removing Barriers to Responsible Research Involving Human
Stem Cells.'' It is our assertion that the order expressed the will of
the American people, Congress, and in particular our generation.
Medical research and clinical advances that would alleviate human
suffering and restore quality of life is a humanitarian concern of
greatest importance to us. Each year, at hundreds of U.S. institutions,
students enter undergraduate, graduate, and medical school programs
designed to fulfill the needs of the biomedical industry. The
biomedical industry is one of the fastest-growing industries nationally
and internationally. Within the biomedical industry, stem cell research
has attracted the excitement of students, researchers, doctors, and
companies. In 2009, the State of California passed Bill 471, ``The
Biomedical Training and Stem Cell Research Education Act'' to ensure
that enough workers would be trained to meet the growing demands of the
regenerative medicine industry. Students believe that the medical
promise of cellular regeneration using stem cells is unparalleled in
human history. This excitement is demonstrated by our decision to
choose medical research projects focusing on stem cell applications, in
which the vast majority of graduate student stipends are funded by NIH
grants. The accelerated development of this new field, unprecedented
State bills to support the research and career training of scientists
and doctors, and the influx of commercial investments are all
indicative of a trajectory consistent with our intuitive assertion that
stem cell research will revolutionize medicine. However, absent the
temporary stay, the recent preliminary injunction turns the field on
its head and is immediately devastating to career development in
regenerative medicine, threatening our generation's long term objective
of finding cures to intractable medical conditions. Federal funding of
human embryonic stem cell research is the will of the people, necessary
for biomedical advance, critical to America maintaining its competitive
advantage, morally and ethically acceptable, and integral to the
education and training of the next generation of scientists and
doctors. Human embryonic stem cells (hESCs) are unique in their use as
biomedical research tools and for their current and eventual clinical
application. HESCs are not supplanted by any other cell source,
including adult stem cells or induced pluripotent stem cells.
Therefore, SSSCR urges Congress to act swiftly and decisively to
legislatively fix our current public policy debacle on funding hESC
research
In the interest of maintaining a strong, healthy, and competitive
Nation we present to Congress the following arguments:
Federal Funding of Human Embryonic Stem Cell Research is the Will
of the American People and Congress.--Poll after poll since the early
2000's has unanimously demonstrated a majority support for hESC
research and Federal funding of the research. State led campaigns in
California, Missouri, and Michigan have sided with the research. In the
most recent poll on the subject conducted in August 2010 by
Research!America, it was found that 70 percent of Americans favor
expanded Federal funding of research using human embryonic stem cells.
Gallup polls from 2005 to 2009 have shown support for fewer
restrictions on hESC research to range between 52-60 percent. In 2006
and 2007, Congress passed Stem Cell Research Enhancement Acts in both
the House and Senate specifically removing Federal funding restrictions
on new stem cell lines. It has been the unambiguous interpretation of
three administrations, the NIH in 1999, congressional votes in 2006 and
2007, and Senate appropriations since 2002, that Federal funding of
hESC research does not violate the Dickey-Wicker amendment. Five
hundred forty-six million dollars in Federal funds has been invested in
hESC research, since 2002, and nearly a decade of scientific advance is
in jeopardy. Projects may be lost forever and millions of taxpayer
dollars wasted. The students engaged in these projects will very likely
have to change their discipline or their careers entirely due to losing
their research stipends.
HESC is Morally and Ethically Acceptable.--It is SSSCR's contention
that a society's highest moral obligation is to treat the sick
medically and with dignity. When a research path presents hope to
millions of patients with debilitating conditions, the only dignified
approach by society and government is to provide that hope by pursuing
promising medical research in an expeditious and ethical manner. SSSCR
feels that the reality of the potential for excess IVF embryos to
generate offspring is often clouded by ideology from those opposing the
research. Scientifically, many of the embryos that would be donated to
research for the generation of new human embryonic stem cell lines are
enviable for implantation and could never lead to a successful
pregnancy. The supply of IVF embryos far exceeds the demand for
reproductive purposes. In a famous RAND corporation study, it was found
that more than 400,000 IVF embryos were still in storage, dating back
to the 1970s. This fact underscores that hESC research does not
necessitate the destruction of any embryo nor has the research
prevented a single pregnancy. The generation of IVF embryos for
reproductive purposes results in excess embryos that will be stored
indefinitely or destroyed. The creation of stem cell lines for research
is a subsequent, determining act that chooses humanitarian benefit over
biomedical waste. Furthermore, prior congressional legislation and the
``New Guidelines on Human Stem Cell Research'' have carefully addressed
ethical considerations by mandating approved lines to have been donated
under informed consent, without financial incentive, and for the embryo
to have been created with reproductive intent, but no longer desired
for such purposes. Therefore, SSSCR feels that it is our society's
moral obligation to conduct hESC research and that the Government has
put in place an appropriate framework for students to ethically
continue our research projects and to pursue our passion for finding
cures.
NIH Funding is Critical to the Education and Training of the Next-
generation of Scientists and Doctors.--The vast majority of biomedical
research conducted at our universities is carried out by graduate and
medical students who depend on a mentor's grant to fund their stipend,
which covers living expenses while completing the biomedical research
program. For fiscal year 2010, the NIH funded $131 million for hESC
research. In total, there are 223 hESC NIH-funded research projects
estimated to support 1,300 jobs. However, the impact can spread beyond
these projects. One example is the UCSF Medical Scientists Training
Programming involving 88 students earning joint M.D. and Ph.D. degrees.
The entire program is in jeopardy of losing NIH funding, since mentors
working with hESCs cannot be separated out based on the interdependency
of the award and the applicant. Twenty-four NIH-funded projects that
are up for $54 million in annual renewal on September 30, 2010, is in
jeopardy if a stay in not continued at the projected September 27
hearing. In future fiscal years, projects up for annual renewal are
also in danger of losing all funding. In all these cases, the immediate
impact of an injunction on Federal funding of hESCs is the imminent
loss of students' stipends. Current students will be financially forced
out of the field to find alternative salary, while new students will be
dissuaded from entering the field, and America will begin to lose its
competitive advantage in science and medicine. It is imperative that
Congress takes action to establish the policy for hESC research
funding, so that we never again jeopardize the future and training of
our young scientists and doctors in this field.
HESCs are Unique in Their Medical Promise and are not Replaced by
Other Types of Stem Cells.--Despite 50 years of research using adult
stem cells, severe limitations have not been overcome, such as growing
them in sufficient numbers for clinical use and continued failure to
treat nonhematological tumors. Pluripotent cells offer a distinct
advantage for neurological conditions where brain biopsies can only be
used for diagnostic purposes and autopsies do not yield viable nerves.
A recent medical advance in reprogramming adult cells back to a
pluripotent state, called induced pluripotent stem cells (iPSCs), is
very promising; however, iPSCs do not replace the need for hESCs in
basic research and clinical application. The industry standard for iPSC
cells is not well-established, resulting in a great deal of inter-lab
variability, and characterization continues to be based on hESC
comparison. Clinically, iPSC cells remain very hazardous and are
unlikely for FDA approval anytime soon. The reprogramming process
involves hazardous viral gene delivery methods and in some cases known
cancer causing genes. While the field hopes to resolve these issues,
it's too early to project confidently their use in the clinic. Much
more basic research needs to be done on both iPSC and hESCs to
understand their biological differences and similarities. Geron has
received FDA approval for clinical trials using hESCs to treat spinal
cord injury. Advanced Cell Technologies is expected to receive FDA
approval to use hESC-derived retinal cells in clinical trials to treat
eye disease. IPSCs do not replace hESCs. Clinical trials with hESCs
have already received FDA approval, while iPSCs remain clinically
hazardous with the current technology.
Our generation has a great responsibility to society to advance
science and medicine. In order to realize the potential of regenerative
medicine and maintain our global scientific leadership, our young
scientists and doctors in training must receive the financial support
to continue their programs. The NIH is critical in this aim and thusly
Federal funding for hESC research must be safeguarded and maintained.
We urge Congress to sort out the legal wrangling and provide our
generation the chance to use hESCs in regenerative medicine to discover
cures for devastating medical conditions.
-