[Senate Hearing 110-208]
[From the U.S. Government Publishing Office]
S. Hrg. 110-208
CAN CONGRESS HELP FULFILL THE PROMISE OF STEM CELL RESEARCH?
=======================================================================
JOINT HEARING
BEFORE THE
COMMITTEE ON HEALTH, EDUCATION,
LABOR, AND PENSIONS
AND THE
SUBCOMMITTEE ON LABOR, HEALTH AND HUMAN SERVICES, EDUCATION AND RELATED
AGENCIES
OF THE
COMMITTEE ON APPROPRIATIONS
UNITED STATES SENATE
ONE HUNDRED TENTH CONGRESS
FIRST SESSION
ON
EXAMINING STEM CELL RESEARCH, FOCUSING ON ONGOING FEDERAL SUPPORT OF
BOTH EMBRYONIC AND NON-EMBRYONIC STEM CELL RESEARCH AND SCIENTIFIC
PROGRESS, INCLUDING RECENT FINDINGS ON AMNIOTIC FLUID STEM CELLS
__________
JANUARY 19, 2007
__________
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COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS
EDWARD M. KENNEDY, Massachusetts, Chairman
CHRISTOPHER J. DODD, Connecticut MICHAEL B. ENZI, Wyoming
TOM HARKIN, Iowa JUDD GREGG, New Hampshire
BARBARA A. MIKULSKI, Maryland LAMAR ALEXANDER, Tennessee
JEFF BINGAMAN, New Mexico RICHARD BURR, North Carolina
PATTY MURRAY, Washington JOHNNY ISAKSON, Georgia
JACK REED, Rhode Island LISA MURKOWSKI, Alaska
HILLARY RODHAM CLINTON, New York ORRIN G. HATCH, Utah
BARACK OBAMA, Illinois PAT ROBERTS, Kansas
BERNARD SANDERS (I), Vermont WAYNE ALLARD, Colorado
SHERROD BROWN, Ohio TOM COBURN, M.D., Oklahoma
J. Michael Myers, Staff Director and Chief Counsel
Katherine Brunett McGuire, Minority Staff Director
(ii)
COMMITTEE ON APPROPRIATIONS
ROBERT C. BYRD, West Virginia, Chairman
DANIEL K. INOUYE, Hawaii THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont TED STEVENS, Alaska
TOM HARKIN, Iowa ARLEN SPECTER, Pennsylvania
BARBARA A. MIKULSKI, Maryland PETE V. DOMENICI, New Mexico
HERB KOHL, Wisconsin CHRISTOPHER S. BOND, Missouri
PATTY MURRAY, Washington MITCH McCONNELL, Kentucky
BYRON L. DORGAN, North Dakota RICHARD C. SHELBY, Alabama
DIANNE FEINSTEIN, California JUDD GREGG, New Hampshire
RICHARD J. DURBIN, Illinois ROBERT F. BENNETT, Utah
TIM JOHNSON, South Dakota LARRY CRAIG, Idaho
MARY L. LANDRIEU, Louisiana KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island SAM BROWNBACK, Kansas
FRANK R. LAUTENBERG, New Jersey WAYNE ALLARD, Colorado
BEN NELSON, Nebraska LAMAR ALEXANDER, Tennessee
Charles Kieffer, Staff Director
Bruce Evans, Minority Staff Director
------
Subcommittee on Labor, Health and Human Services, Education, and
Related Agencies
TOM HARKIN, Iowa, Chairman
DANIEL K. INOUYE, Hawaii ARLEN SPECTER, Pennsylvania
HERB KOHL, Wisconsin THAD COCHRAN, Mississippi
PATTY MURRAY, Washington JUDD GREGG, New Hampshire
MARY L. LANDRIEU, Louisiana LARRY CRAIG, Idaho
RICHARD J. DURBIN, Illinois KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island TED STEVENS, Alaska
FRANK R. LAUTENBERG, New Jersey RICHARD C. SHELBY, Alabama
ROBERT C. BYRD, West Virginia (ex
officio)
Professional Staff
Ellen Murray
Erik Fatemi
Mark Laisch
Adrienne Hallett
Lisa Bernhardt
Bettilou Taylor (Minority)
Sudip Shrikant Parikh (Minority)
Administrative Support
Teri Curtin
Jeff Kratz (Minority)
?
C O N T E N T S
----------
STATEMENTS
FRIDAY, JANUARY 19, 2007
Page
Kennedy, Hon. Edward M., Chairman, Committee on Health,
Education, Labor, and Pensions, opening statement.............. 1
Enzi, Hon. Michael B., a U.S. Senator from the State of Wyoming,
opening statement.............................................. 3
Harkin, Hon. Tom, a U.S. Senator from the State of Iowa.......... 4
Specter, Hon. Arlen, a U.S. Senator from the State of
Pennsylvania................................................... 6
Landis, Story C., Ph.D., Director, National Institute of
Neurological Disorders and Stroke (NINDS), Department of Health
and Human Services, Washington, DC............................. 7
Prepared statement........................................... 9
Daley, George Q., M.D., Ph.D., Associate Professor of Pediatrics,
Children's Hospital, Boston, MA................................ 13
Prepared statement........................................... 15
Stanford, Lauren, Juvenile Diabetes Patient, Plymouth, MA........ 16
Wagner, John E., Jr., M.D., Professor of Pediatrics, University
of Minnesota Medical School, Minneapolis, MN................... 19
Prepared statement........................................... 21
ADDITIONAL MATERIAL
Statements, articles, publications, letters, etc.:
RAND Research Brief.......................................... 35
Letter from David A. Prentice and Gene Tarne with supporting
materials.................................................. 51
Response to Questions of Senator Enzi by George Q. Daley,
M.D., Ph.D................................................. 76
Response to Question of Senator Cochran by George Q. Daley,
M.D., Ph.D................................................. 77
Response to Questions of Senator Enzi by Lauren Stanford..... 77
Response to Questions of Senator Enzi by John E. Wagner, Jr.,
M.D........................................................ 78
Response to Questions of Senator Cochran by John E. Wagner,
Jr., M.D................................................... 79
(IV)
CAN CONGRESS HELP FULFILL THE PROMISE OF STEM CELL RESEARCH?
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FRIDAY, JANUARY 19, 2007
U.S. Senate,
Committee on Health, Education, Labor, and Pensions,
Committee on Appropriations,
Subcommittee on Labor, Health and Human Services,
Washington, DC.
The committees met, pursuant to notice, at 9:33 a.m. in
Room SD-192, Dirksen Senate Office Building, Hon. Edward
Kennedy, presiding.
Present: Senators Kennedy, Harkin, Brown, Lautenberg, Reed,
Sanders, Enzi, Specter, Stevens, Isakson, Murkowski, Coburn,
Hatch, and Allard.
Opening Statement of Senator Kennedy
The Chairman. Good morning. We'll come to order.
This is a very special day for not only the very important
subject that we're considering, stem cell research, but for
those of us on these two committees: our Health, Education,
Labor, and Pensions Committee, and the Appropriations
Committee, which Senator Harkin and Senator Specter are leaders
in the Senate and have done an extraordinary job over the
period of these years, in terms of giving focus and life to
this subject matter. We're all partners, working closely
together. We have a great admiration for the leadership that
Senator Harkin and Senator Specter have provided in moving us
all toward this place where we are today, really on the eve,
almost, of Senate consideration of this legislation. And we're
enormously grateful to my colleague and friend Senator Enzi,
who has been the chairman of our committee, and who is my
partner in so many of these health issues and has been a valid
and important ally in this undertaking.
So, I'll make a brief comment and ask my colleagues if they
would be good enough to say a brief word, and we'll move
forward with a very, I think, distinguished panel that can be
very helpful in bringing us up to date with the great sense of
opportunity about stem cell research.
Today's hearing is really about hope. And hope is what stem
cell research brings to millions of Americans who seek cures
for cancer, diabetes, spinal cord injury, many other serious
conditions--hope for those with Parkinson's disease--the
tremors of that disease can be cured; hope that spinal injury--
spinal cord injuries can be healed; hope for children with
diabetes. The constant worry and vigilance required to cope
with their disease will be a thing of the past.
A week ago, a solid bipartisan majority, in the House of
Representatives, voted for hope and new progress in these
battles against illness, by approving legislation to unlock the
potential of stem cell research. Now the challenge is before
the Senate, and we, too, must respond. Many of the Senate's
staunchest of supporters of stem cell research are here today.
We represent diverse backgrounds and many faiths. We have come
to our support of stem cell research by different paths, but we
have all concluded that this research is one of the great
potential breakthroughs of modern medicine, that it brings the
potential of fuller, longer life for countless people who
suffer from debilitating diseases.
Many of those who oppose this research are here today, too,
and we welcome their perspective. Those who oppose the research
do so out of deeply held moral convictions, and we respect
their views, even as we differ with them. Today, we'll also
hear from the leading scientists about recent advances in stem
cell research, their potential to help Americans whose lives
have been devastated by disease and injury. Some have suggested
these new developments avoid the need for the use of stem cells
derived from embryos, and we will hear the scientific
community's evaluation of that possibility.
We welcome Dr. Story Landis, who will be the director of
the--she is the director of the National Institute of
Neurological Diseases and Stroke, as well as Dr. George Daley,
of the Children's Hospital in Boston, Dr. George Wagner, the
University of Minnesota. All of them are leaders in the field
of stem cell research.
But today's hearing is not just a celebration of research,
it's a call for change in the search for new cures that have
been severely limited by the restrictions that President Bush
imposed on stem cell research 6 years ago when he limited the
use of funds to the inadequate number of cell lines existing at
the time. Last year, President Bush vetoed the bipartisan
legislation to end those restrictions and offer the hope of
fuller and longer lives to millions of our citizens.
Today, we'll hear of that hope from Lauren Stanford, of
Plymouth, Massachusetts. We'll hear of her courage and dignity
in the face of diabetes. I was profoundly moved by the letter
that she sent me during the stem cell debate, last year,
describing her hope that stem cell research might allow her to
live a future free of her illness. I'm sure our colleagues on
our two committees will welcome the opportunity to hear her
words, too.
Lauren is not alone. She joins Nancy Reagan, dozens of
Nobel laureates, thousands of scientists, millions of patients
across the Nation, in calling for an end to the restrictions
that have hobbled the search for new cures. The debates that we
have held in recent years have already led many of our
colleagues who opposed the research in the past to support it
now. It may be too much to hope that President Bush will join
those ranks, but if he could be here today to hear the hopes
and dreams of patients like Lauren, surely he would have to re-
examine his conscience and reconsider the restrictions imposed
on the research. Let us all hope that, in a private moment, the
President will undertake that re-examination and signal the
acceptance of our new bipartisan stem cell legislation and the
hopes of millions of Americans it represents.
Time has come for Congress and the President to join
together to unchain the creative energies of America's
scientists and allow them to pursue the promise of stem cell
research. There could be fewer greater triumphs of bipartisan
progress than to have the Stem Cell Research Enhancement Act
signed into law.
Senator Harkin.
Senator Enzi.
Opening Statement of Senator Enzi
Senator Enzi. Thank you, Mr. Chairman, for holding this
hearing. I want to thank the witnesses for coming.
Throughout the history of our Nation, generations of
American scientists have looked for ways to improve human
condition and address the problem of disease and afflictions of
old age. As they conducted their research, each scientist's
work built on the discoveries that preceded it, and the results
they achieved over the years have enabled us to live longer,
healthier, more productive lives. From time to time, there's a
breakthrough, or possible breakthrough, in medical science that
has the potential to revolutionize not only our ability to
diagnose or treat an affliction, but our basic understanding of
how the human body operates. When that occurs, a debate ensures
as society attempts to evaluate the new procedure's potential
to address the diseases that threaten our health, as well as
the ethics of putting the new procedures into practice. Such a
possible breakthrough is stem cell research.
At present, its promise and potential for changing the way
we view health and disease seems limitless. In theory, stem
cells may be capable of doing everything we can possibly
imagine, and more. Unfortunately, there's often a wide gap
between what's possible in theory and what's practical and
possible in the real world. What the future of stem cells will
be, no one knows for certain. Still, the possibilities are more
than intriguing, and certainly worth an in-depth look.
The research that's been conducted into stem cells so far
has been so exciting because of the very nature of these cells.
Stem cells have the capacity to renew themselves and then
become specialized cells. Most of the cells that are in the
body are created and committed to performing a specific
function. The stem cell remains on the fence, uncommitted,
until given a signal by the body to develop into a specialized
cell. We've all heard the saying, ``You don't have to be a
weatherman to know which way the wind's blowing.'' As for the
research, however, you really do need a strong background in
science to understand fully the specifics of stem cell research
and its implications for the future.
Fortunately, we're not here to predict the impact stem
cells will have on the healthcare system in the years to come,
we're here to discuss if it is appropriate to use Federal
taxpayer dollars to finance additional work in this area, and
there is a big difference. In discussing stem cell today, we're
not making a judgment about the science itself; rather, we're
considering what science should be supported by Federal
taxpayer dollars. We're considering the appropriate political
oversight and public fiscal support of the work of those
scientists in manipulating and possibly even destroying the
basic building blocks of human life. We're considering if we
should pass legislation that will be vetoed by the President or
legislation that will move this research field forward. We're
reaffirming how we, as a society, view the human embryo and its
function. Without question, science must be guided by morality.
There have been too many instances, over the course of human
history, in which terrible things have been done in the name of
science.
In determining how to proceed, we, of course, must consider
the promise of stem cell research generally and embryonic stem
cell really specifically. But, in considering that promise, we
must make it clear that, while stem cells may someday lead to
therapeutic advancements for devastating diseases, like
Alzheimer's, diabetes, Parkinson's, leukemia, and spinal cord
injuries, that that day has not come. We must be careful not to
oversell the promise of this research to the American people.
While several nonembryonic stem cell therapies are now in
practice, every reputable scientist will admit that possible
cures or advanced treatment, using embryonic stem cells are
many years away. So, while the research provides great hope for
millions of Americans, at this point the full benefits have not
been realized. They fire our imagination as we consider the
possibilities that may or may not come to pass. If we truly
trust science, then we should give science a chance to solve
the dilemma before we reach the issue of public funding of
embryonic stem cell research.
As outlined by the report from the President's Council on
Bioethics, and is highlighted again with the recent
announcement by Dr. Atala and others, related to amniotic stem
cells--researchers are exploring a multitude of different ways
by which we can create embryonic-like stem cell lines without
harming or destroying embryos. Further, States and private
research organizations are already plowing billions of dollars
into human embryonic stem cell research that goes beyond the
parameters of President Bush's policy. Let those efforts
continue while we continue working in Congress to support stem
cell research that doesn't involve harming or destroying an
embryo, which is something that the vast majority of Americans
could support.
Thank you all for coming today. I look forward to the
ongoing discussion.
The Chairman. Thank you very much, Senator Enzi.
And, as I mentioned earlier, Senator Harkin and Senator
Specter played a special role in keeping this issue in the
forefront here in the Senate, and we work very closely
together. We're delighted that we've been able to work so that
the members of both committees could hear our excellent
witnesses.
Senator Harkin.
Opening Statement of Senator Harkin
Senator Harkin. Well, thank you very much, Mr. Chairman.
You've been a leader on so many health issues for so many
years, and I want to thank you for suggesting that we team up
our two committees together on this joint hearing.
This marks the 20th hearing that Senator Specter and I have
held on human embryonic stem cells, dating back to December
1998, 1 month after Dr. Jamie Thompson, from the University of
Wisconsin, announced that he had isolated them, for the first
time ever. Since that time, I've talked to hundreds of patients
and their family members about their hopes for this research.
I've visited laboratories and talked to scientists. I've heard
from ethicists and religious leaders. And every day, I become
more and more convinced that we, in Congress, need to do all we
can to promote this possible life-saving, life-enhancing
research.
Meanwhile, the opponents have become more and more
desperate. We saw that earlier this month during the hysteria
over Dr. Anthony Atala's new research on amniotic stem cells.
Opponents breathlessly claimed that, on the basis of this one
paper, embryonic stem cell research should be abandoned, even
though Dr. Atala himself completely disagrees with that
conclusion. Dr. Atala wrote, ``It is essential that National
Institutes of Health-funded researchers are able to fully
pursue embryonic stem cell research as a complement to research
into other forms of stem cells.''
That's a direct quote from Dr. Atala.
A few days later, the White House released a 60-page
polemic against embryonic stem cell research, in which it
touted research by Dr. Kevin Eggan, of Harvard, who testified
before our subcommittee last year. Here's what Dr. Eggan wrote
in response to that White House report. And Dr. Eggan was just
in my office last week to substantiate it further. But here's
what Dr. Eggan wrote,
``We are disappointed that the White House Office of Domestic
Policy gave us no opportunity to correct the report's clear
misrepresentation of our work. On the contrary, we assert that
human embryonic stem cells hold great promise to find new
treatments and cures for diseases, and we support the Stem Cell
Research Enhancement Act.''
The House overwhelmingly passed that bill earlier this
month, and the Senate will pass it soon. There's no question
about that. The only question is what the President will do
when the bill reaches his desk. Most people assume that he'll
veto it. I'm not so sure.
Earlier this month, White House spokeswoman Jeannie Mamo
was quoted in a Gannett news story as saying this about stem
cell research,
``The President has said that, after careful and thoughtful
deliberation with government and outside experts, there was
only one moral line he said he would not cross, and that is
that Federal taxpayer dollars should not be used in the
destruction of embryos.''
Well, this is a very interesting statement, because, if
it's true, the President should have no problem signing our
bill. S. 5 would not allow Federal funding to be used for the
destruction of embryos. That's prohibited by what's called the
Dickey Amendment, which is included every year in our
appropriations bill. Our stem cell bill doesn't have anything
to say about the Dickey Amendment. We're only talking about
using embryos that are going to be destroyed anyway. Every day,
IVF clinics discard embryos that are no longer needed for
fertility treatments. All we're asking is to use stem cells
from some of those excess embryos for research that would save
people's lives. No Federal tax dollars would be used to derive
the stem cells. That work would be done using non-Federal
funding.
So, either this spokeswoman misrepresented the President's
position, in which case, I assume she's been taken out to the
woodshed, or the White House just opened the door to signing
our bill. And I hope it's the latter. I hope that President
Bush will listen to the scientists at NIH and elsewhere, so
many Nobel laureates all around this country and around the
world, who want this research to proceed. Most important, I
hope he'll listen to millions of Americans who suffer from
juvenile diabetes and spinal cord injuries and ALS and
Parkinson's and cancer, who view this stem cell research as
their best hope for a treatment or a cure.
I want to thank all the witnesses who have taken the time
to give testimony before us today. We have an outstanding group
of scientists, all of whom I've met before at some point over
the years. I hadn't met Lauren Stanford until this morning, but
I feel like I know her, because Senator Kennedy and I talked
about her a lot on the Senate floor last year, and I believe
her story helped us pass H.R. 810, and will do so again.
So, again, Mr. Chairman, thank you very much. I look
forward to the testimony of our witnesses.
The Chairman. Senator Specter.
Opening Statement of Senator Specter
Senator Specter. Thank you, Mr. Chairman.
I believe that we are setting a record here this morning,
on a Friday, in the U.S. Senate, to have 13 Senators present
for a hearing. I believe that is solid testimony to the
importance of this subject, and I believe it signifies a
tremendous interest in utilizing Federal funds for embryonic
stem cell research.
We found out about stem cells when the scientists told us
about them in November 1998, and, within a few days, the
appropriations subcommittee held the first hearing, in this
room, and this is our 20th hearing. And I believe that sets
something of a record, too.
I agree with Senator Kennedy on his call for hope. I would
supplement that with a call for political pressure. We are
within close range of overriding a presidential veto. Sixty-
three Senators voted in favor of use of Federal funds for
embryonic stem cell research last year, and we're within
shouting distance, in the House, of having enough votes to
override a presidential veto.
Sometimes we forget that we live in a representative
democracy, and that means that the people decide what the
government is going to do. We had a clarion call on that, on
the last election, where the American people spoke out on Iraq.
I'm not sure that it's been heard in all quarters, but the
American people did speak out. And they also spoke out, in a
number of States, on the issue of stem cell research. And I
believe, if some of the Republican candidates, to put it
candidly and bluntly, had been for stem cell research, I'd
still be chairman of the Judiciary Committee.
[Laughter.]
Now, it's a very basic matter of fact that there are
400,000 embryos that are frozen, and almost all of them will be
thrown away if they're not used. The subcommittee put up $2
million for an embryo adoption program, and, since that time,
only about 100 have been adopted. So, it's a simple matter of
either to use them or lose them. If these embryos were going to
create life, no one would be in favor of using them for
research. And as Senator Harkin points out, this bill clearly
does not allow Federal funding for the destruction of embryos.
We have increased NIH funding on initiatives originating in
this room with our subcommittee, raising the funding from $12
to $29 billion, and it is scandalous that those funds are not
available for embryonic stem cell research. In 1970, President
Nixon declared war on cancer, and, had we pursued that war with
the same intensity we pursue other wars, cancer would have been
cured by now. And, frankly, I'm madder than hell about our
failure to prosecute that war. I'm one of the victims of the
failure to prosecute that war. I have urged the advocacy groups
to organize a million-person march on the Mall loudly enough to
be heard in the second floor of the living quarters of the
White House. It's close to the Mall. And it is really
reprehensible that the National Cancer Institute was cut last
year by $50 million, which goes to the NIH funding issue and
the stem cell issue. But I think that, properly organized and
with the pressure being put on the Members of Congress who have
voted no, and ultimately on the White House, it's a matter of
when, not if, we'll be using Federal funds for embryonic stem
cell research.
Thank you, Mr. Chairman.
The Chairman. Thank you very much.
Our first witness, Story Landis, who's the director of the
National Institute of Neurological Disorders and Stroke. Dr.
Landis has been the director since September 1, 2003, and, as
director of NINDS, Dr. Landis oversees an annual budget of a
billion and a half dollars and a staff of more than 900
scientists--physicians, scientists, and administrators. The
Institute supports research by investigators, public and
private institutions across the country, as well as by
scientists working in intramural laboratories and branches in
Bethesda, Maryland. The Institutes' mission is to reduce the
burden--neurological disease, a burden borne by every age
group, by every segment of society, by people all over the
world.
Ms. Landis, thank you very much for being here.
Ms. Landis. Thank you very much----
The Chairman. We look forward----
Ms. Landis [continuing]. For inviting me.
The Chairman [continuing]. And for your service.
STATEMENT OF STORY C. LANDIS, PH.D., DIRECTOR, NATIONAL
INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS),
DEPARTMENT OF HEALTH AND HUMAN SERVICES, WASHINGTON, DC
Ms. Landis. Mr. Chairman, Senator Specter, Senator Enzi,
and members of the subcommittee, I'm pleased to appear before
you today to testify about the science of stem cell research. I
look forward to discussing the compelling need to pursue both
embryonic and nonembryonic stem cell research and the
scientific challenges and progress, including a recently
published scientific finding on amniotic-fluid stem cells.
So, both embryonic and nonembryonic stem cells show promise
for developing treatments for human diseases and injuries, and
at the present time, we can't predict which type of stem cell
will be best for treating a given disease, nor, to be perfectly
honest, is it likely that any one type of stem cell will be
best for all uses of stem cells. Therefore, NIH should support
research on stem cells from both embryonic and other sources.
Now, the most obvious use of stem cells, which has captured
the public's attention, is to replace specific types of cells
which are damaged by disease or injury, and my written
testimony describes recent progress in preclinical animal
studies using embryonic stem cells to replace dopamine-
producing nerve cells that are lost in Parkinson's, motor
neurons, and supporting cells that are damaged in spinal cord
injury, and liver cells that are affected by chronic liver
diseases.
However, beyond replacing cells or tissue, stem cell
biology has many other potential applications. We could, for
example, speed drug development by testing potential drugs in
cell culture on specific kinds of human cells that are affected
by disease, and stem cells represent a source of the necessary
cells.
Studies of human embryonic stem cells also yield
information about the complex events that occur during human
development, including the molecular mechanisms through which
these pluripotent cells generate the hundreds and thousands of
different kinds of cells that make up the human body. This
knowledge will not only help us control stem cells from both
embryonic and nonembryonic sources, but also will help us
better understand the cause of many diseases, and that, in
turn, will lead to more effective treatments.
Finally, another potential application of stem cell biology
is to learn how to encourage the stem cells that are present in
even the adult human brain to repair damage. And this approach
has recently shown promise in animal experiments in Parkinson's
disease and also stroke.
But to realize the potential promise, the promise of stem
cell biology for treating disease, scientists must learn how to
reliably manipulate stem cells to have the characteristics
necessary for each of these applications. We have to learn how
to control stem cell proliferation to generate sufficient
quantities of cells, we have to learn how to control their
differentiation, create recipes for specific classes of cells.
We also have to enable stem cells to survive after we
transplant them, to integrate into the surrounding tissue, and
to function for extended periods of time. Finally, we must
control stem cell behavior to avoid harming the recipient,
whether by generating tumors--and I'm sure this is an issue
that will come up--by forming faulty nerve cell connections, or
in any other way.
I'd like to speak briefly about amniotic-fluid-derived stem
cells. This is a topic that's received a great deal of
attention recently.
In a recently published article in Nature Biotechnology,
Dr. Atala and his colleagues at Wake Forest University
described how they isolated and characterized stem cells from
the amniotic fluid that cushions the developing fetus in the
uterus. This fluid is collected from pregnant women during
amniocentesis, when they ask to be tested for a variety of
congenital and developmental diseases and disorders.
Now, scientists had previously shown that some of these
cells could turn into fat cells, muscle cells, bone cells, and
cells of the nervous system, but what Dr. Atala has done is to
devise a method to select, from those multiple kinds of cells
in the fluid, those cells which have the most stem-cell-like
property, and then, also, he has extended our understanding of
the kinds of properties of these cells, and what they can turn
into.
So, he and his colleagues have demonstrated that amniotic-
fluid-derived stem cells could produce several different adult
cell types--nerve cells, liver, cells, bone-forming cells--and,
in the case of nerve cells, that they make proteins
characteristic of nerve cells and that they can be integrated
into the nervous system, that they're self-renewing and
maintain the normal number of chromosomes. But these cells are
not equivalent to pluripotent embryonic stem cells. They have
some of the properties, but not all. And, as we've already
heard, he has concluded that these cells complement, but do not
replace, human embryonic stem cell research.
So, in conclusion, NIH places a very high priority on both
embryonic and nonembryonic stem cell research that will be
useful for basic, translational, and clinical studies. Science
works best when scientists can pursue all avenues of research.
And if I could be so presumptuous as to borrow a metaphor that
Senator Harkin used in hearings in 1997 on the importance of
funding basic science research, if the cure for Parkinson's
disease or juvenile diabetes lay behind one of four doors,
wouldn't you want the option to open all four doors at once
instead of one door? And stem cell research is the same.
Thank you very much.
[The prepared statement of Ms. Landis follows:]
Prepared Statement of Story C. Landis, Ph.D.
OPENING REMARKS
I am pleased to appear before you today to testify about the
science of stem cell research. I look forward to discussing ongoing
Federal support of both embryonic and nonembryonic stem cell research
and scientific progress, including the recently published findings on
amniotic-fluid stem cells and other studies raising the possibility
that nonembryonic stem cells have similar properties allowing them to
differentiate into many different cell types.
the need for research to explore the potential of human stem cells
Stem cells are cells that can multiply without changing, that is,
self-renew, or can differentiate to produce specialized cell types.
Stem cells have been derived from both embryonic and nonembryonic
tissues, and these cells have different characteristics. Both embryonic
and nonembryonic stem cells show potential for developing treatments
for human diseases and injuries. Because of this, this Administration
in 2001 became the first to fund research on human embryonic as well as
adult stem cells. There are many ways in which human stem cells might
be used in basic and clinical research. However, only further research
will overcome the technical hurdles between the potential of stem cells
and the realization of these uses.
The most obvious potential application of human stem cells would be
the generation of cells and tissues for cell-based therapies. Stem
cells, directed to differentiate into specific cell types, offer the
possibility of a renewable source of replacement cells and tissues to
treat a number of common diseases and disorders, including Parkinson's
disease, spinal cord injury, stroke, burns, heart disease, diabetes,
osteoarthritis, and rheumatoid arthritis.
To realize the potential of stem cell-based therapies for pervasive
and debilitating diseases, scientists must learn to reliably manipulate
stem cells so that they possess the necessary characteristics for
successful differentiation, transplantation, and engraftment. Although
scientists are making progress, we cannot yet control the
differentiation of stem cells adequately. To be useful for transplant
purposes, stem cells must:
Proliferate extensively and generate sufficient quantities
of specialized cells.
Differentiate into the desired cell type(s).
Survive in the recipient after transplant.
Integrate into the surrounding tissue after transplant.
Function appropriately for extended periods of time.
Avoid harming the recipient in any way.
Stem cells have many other potential uses. Studies of human
embryonic stem cells, for example, yield information about the complex
events that occur during the initial stages of human development. A
primary goal of this research is to identify the molecular mechanisms
that allow undifferentiated stem cells to differentiate into one of the
several hundred different cell types that make up the human body.
Scientists know that turning genes on and off is central to this
process. A significant challenge for stem cell research is that
scientists do not yet fully understand the signals that turn specific
genes on and off to influence the differentiation of the stem cell into
a specialized cell with a specific function, like a nerve cell. This
knowledge not only offers the opportunity to learn how to control stem
cells from both embryonic and nonembryonic sources, but also to better
understand the cause of a number of serious diseases, including those
that affect infants and children, which in turn could lead to new and
more effective intervention strategies and treatments.
Among other applications, human stem cells could also be used to
speed the development of new drugs. Initially testing thousands of
potential drugs on cells in cell culture is potentially far more
efficient than testing drugs in live animals. In vitro systems are
useful in predicting in vivo responses and provide the benefits of
requiring fewer animals, requiring less test material, and enabling
higher throughput. New medications could be tested for safety on the
specific types of human cells that are affected in disease by deriving
these cells from human stem cell lines. Other kinds of cell lines are
already used in this way. Cancer cell lines, for example, are used to
screen potential antitumor drugs. The availability of useful stem cell
lines could allow drug testing in a wider range of cell types. However,
scientists must learn to control the differentiation of stem cells into
the specific cell type on which drugs will be tested.
FEDERAL FUNDING OF STEM CELL RESEARCH
NIH has acted quickly and aggressively to provide support for this
research in accordance with the President's 2001 stem cell policy.
Since 2001, NIH has invested nearly $3 billion on all forms of stem
cell research. Within this total, NIH has contributed more than $130
million in research studying human embryonic stem cells, more than $1.1
billion on research using human nonembryonic stem cells, nearly $509
million on nonhuman embryonic, and more than $1.2 billion on nonhuman
nonembryonic stem cells.
Additionally, in fiscal year 2007, it is projected that NIH will
spend more than $30 million on human embryonic stem cell research and
about $200 million on human nonembryonic stem cell research, while also
investing nearly $100 million on nonhuman embryonic stem cell research
and more than $270 million on nonhuman nonembryonic stem cell research.
In addition to this ample support, NIH has encouraged stem cell
research through the establishment of an NIH Stem Cell Task Force, a
Stem Cell Information Web Site, an Embryonic Stem Cell Characterization
Unit, training courses in the culturing of human embryonic stem cells,
support for multidisciplinary teams of stem cell investigators, and a
National Stem Cell Bank and Centers of Excellence in Translational
Human Stem Cell Research, as well as through extensive investigator
initiated research. NIH determined that access to hESC lines listed on
the NIH Stem Cell Registry and the lack of trained scientists with the
ability to culture hESCs were obstacles to moving this field of
research forward. To remove these potential barriers, the National Stem
Cell Bank and the providers on the NIH Stem Cell Registry together have
currently made over 700 shipments of the hESC cell lines that are
eligible for Federal funding, as posted on the NIH Stem Cell Registry
Web site. In addition, the NIH-supported hESC training courses have
taught over 200 scientists the techniques necessary to culture these
cells. We plan to continue to aggressively fund this exciting area of
science.
NIH-supported scientists have developed efficient techniques to
derive dopamine-producing nerve cells from human embryonic stem cells.
The loss of dopamine-
producing nerve cells is responsible for the movement problems of
Parkinson's disease. When grafted into the brain of a rat model for
Parkinson's disease, the stem cell-derived dopamine cells significantly
improved the animals' movement. However, after 3 months of
transplantation, the scientists found that treated rats' brains
contained groups of undifferentiated cells that had become tumors.
(Nature Medicine 12:1259-1268, laboratory of S. Goldman). This had not
been observed in other studies that transplanted neural stem cells and
emphasizes the need for scientists to learn to better regulate cell
division in transplanted pluripotent stem cells, whatever the source,
before they may serve as a renewable source of replacement dopamine-
producing nerve cells to treat Parkinson's disease in humans. These
results demonstrate both the potential and the challenge of stem cell
research.
In recent years, NIH-supported scientists have demonstrated that
even the adult human brain can generate new nerve cells. Studies
focused on encouraging the innate potential of stem cells that are
normally present in the adult brain are another avenue of research that
has also shown potential for treating Parkinson's disease. In recent
experiments, researchers used drugs to activate adult stem cells in the
brains of adult rats with experimental Parkinson's disease, which
increased the proliferation of replacement cells and improved movement
(The Journal of Neuroscience 26:7272-7280, laboratory of C. Eckman).
Currently, scientists are also using stem cells from a variety of
sources to help animals with spinal cord injuries regain movement.
Human embryonic stem cells have been coaxed into becoming a type of
cell that repaired damaged nerve fiber insulation called myelin (The
Journal of Neuroscience 25:4694-4705, laboratory of H.S. Keirstead).
Human nonembryonic-neural stem cells helped replace damaged rat spinal
cord nerve cells and myelin (Proceedings of the National Academy of
Sciences of the USA 102:14069-14074, laboratory of A.J. Anderson). NIH-
supported scientists now report that they can use mouse embryonic stem
cells to make functional motor neurons, which are the spinal cord cells
that send long nerve fibers called axons (the threadlike extensions on
a neuron, or nerve cell, which conducts nerve impulses) to connect with
leg muscles and other muscles used to move the body. The scientists
combined several methods to coax the mouse embryonic stem cells to
become motor neurons, to overcome molecules that restrain axon growth
in adults, and to attract the motor neuron axons to the correct
muscles. Previously paralyzed rats treated with the motor neurons were
able to move their legs again, although they could not walk or grip
with their feet as well as uninjured rats. This research gives
scientists insight on how they might one day replace human motor
neurons damaged by spinal cord injuries and motor neuron diseases such
as Lou Gehrig's disease (amyotrophic lateral sclerosis, or ALS) and
spinal muscular atrophies. (Annals of Neurology 60(1)32-44, laboratory
of D. Kerr)
Japanese and NIH-funded scientists used mouse embryonic stem cells
to make liver-like cells to create an implantable bioartificial liver.
Chronic liver diseases such as cirrhosis and hepatitis affect 25
million Americans and scientists hope to overcome the shortage of
organs available for transplants by using liver cells derived from stem
cells to replace lost liver function. This implanted device uses liver
cells to replace some liver function. Ninety percent of mice with liver
failure that were implanted with the bioartificial liver survived at
least three times longer than the untreated mice. If scientists can
repeat these results with liver cells made from human stem cells, the
technique offers potential both to individuals born with liver problems
and to those who develop liver disease later in life. (Nature
Biotechnology 24:1412-1419, laboratory of I. Fox).
AMNIOTIC-FLUID-DERIVED STEM CELLS
As you all know, there has been much interest in the recently
published article in Nature Biotechnology by Dr. Anthony Atala and
colleagues at Wake Forest University regarding stem cells isolated from
the amniotic fluid that cushions the developing fetus in the uterus.
Amniotic fluid is collected from pregnant women during amniocentesis to
test for a variety of congenital and developmental diseases and
disorders. Scientists have previously reported that some of these cells
can differentiate into fat, muscle, bone, and nerve cells. Dr. Atala's
work extends our knowledge of the properties of these amniotic-fluid-
derived stem cells (AFS).
Dr. Atala and colleagues showed that AFS could produce cells that
originate from each of the three embryonic germ layers that give rise
to all of the cells in the body. More specifically, the scientists were
able to develop in vitro conditions that produced nerve cells, liver
cells, and bone-forming cells from AFS. The AFS-derived human nerve
cells were able to make proteins typical of specialized nerve cells and
were able to integrate into a mouse brain and survive for at least 2
months, although it is not yet clear whether these cells have all the
properties of normal neurons. They also showed that AFS cells were also
self renewing and maintained the normal number of chromosomes after a
long time in culture over many cell divisions. However,
undifferentiated AFS did not make all of the proteins expected in
embryonic stem cells, and they were not shown to form a teratoma (a
germ cell tumor), one of the essential characteristics of embryonic
stem cells. Thus, given the characteristics of AFS, scientists conclude
that these cells may be multipotent rather than pluripotent. Although
scientists do not yet know how many different cell types AFS are
capable of generating, banked AFS may one day enable the generation of
tissue-matched cells for transplantation into humans.
CONCLUSION
Since 2001, NIH has aggressively pursued research using embryonic
and nonembryonic stem cells that will be useful for basic,
translational, and clinical studies. We are continuing to move this
research forward through training programs, the establishment of the
NIH stem cell characterization unit, and the many grants that have been
made to scientists to explore stem cell research. With NIH support,
scientists have already made remarkable progress in understanding human
embryonic stem cells, and we will provide continued support for these
research efforts, consistent with Administration policy.
I will be more than happy to answer any questions.
The Chairman. Thank you very much.
I'm going to ask if you'd be joined by George Daley, who's
the associate professor at Harvard Medical School, President-
elect of the International Society of Stem Cell Research;
Lauren Stanford, to join you--Lauren Stanford, who has
courageously fought juvenile diabetes and her letter has moved
the entire Senate; and Dr. John Wagner, who's a professor of
pediatrics, University of Minnesota, an internationally
respected researcher--stem cells. And we'll hear from them, and
then have the questions from the committees--for any of our
panelists.
We'll start with Dr. Daley, if you'd be good enough--
please----
Dr. Daley. Thank you.
The Chairman [continuing]. Welcome, from Boston.
Dr. Daley. Thank you, Senator Kennedy. I appreciate the
opportunity to speak here. I was given the instructions that I
could not read my testimony, so I will not.
The Chairman. That's right.
Dr. Daley. I just have some notes.
The Chairman. Well, we're trying something--there are a lot
of people around that come up here and don't know a great deal
about it, and they spend a lot of time reading long
dissertations on it that are rather dull and----
Dr. Daley. Yeah.
The Chairman [continuing]. Not terribly informational.
[Laughter.]
Dr. Daley. I----
The Chairman. And our staffs could work out of that, so----
Dr. Daley [continuing]. I'm worried----
The Chairman [continuing]. We have a rule on our commit-
tee----
Dr. Daley. I'm certainly worried about being dull.
The Chairman [continuing]. That unless you can speak on
your subject for 5 minutes, we're not going to spend the time.
If you want to file other statements--but that is not----
Dr. Daley. Thank you.
The Chairman [continuing]. Guidance for any--we have a
brilliant panel here.
[Laughter.]
And some of us have read extensively about your works,
and----
Dr. Daley. Well----
The Chairman [continuing]. Are enormously grateful. I
just----
Dr. Daley [continuing]. At the risk of being dull----
The Chairman. Well, I'd divert you for 1 minute. I do have
to mention about getting testimony in on time. We are really
going to try and do this. It makes a great deal of difference
to our ability to prepare. And, in this instance, some of the
material didn't get in until 8:30 last evening, and we were in,
ourselves, late. We're really going to insist on that for our
hearings in the future, and we are going to let people know, in
the future, that we are going to insist on it.
But I thank all of you. It was basically the NIH, and--I've
been around here long enough--it isn't NIH, it's OMB clearing
NIH, so I--we know who the culprits are. So----
[Laughter.]
Culprits be warned.
Dr. Daley----
Dr. Daley. OK.
The Chairman [continuing]. Carry on, please.
Dr. Daley. Thank you very much.
STATEMENT OF GEORGE Q. DALEY, M.D., PH.D., ASSOCIATE
PROFESSOR OF PEDIATRICS, CHILDREN'S HOSPITAL,
BOSTON, MA
Dr. Daley. As you said, I'm here as a physician scientist
from Children's Hospital, Harvard Stem Cell Institute. I am the
President-elect of the International Society for Stem Cell
Research, and I'm here representing the American Society of
Cell Biology, whose 10,000 members include some of the world's
leading stem cell scientists.
And I was asked to make some comments that would be
pertinent to the current aspects of the stem cell debate, and
to re-inforce the need for expanded funding for embryonic stem
cell research.
The media has covered a remarkable array of supposed
breakthroughs over the last many years that purport to announce
cells that could replace the need for embryonic stem cells in
research. A number of years ago, it was the multipotential
adult progenitor cell from Catherine Verfaillie's lab in
Minnesota; we'll hear more about that in the coming days. Then
it was the fat stem cell, and clearly there's a lot of fat stem
cells around. And then it was umbilical-cord-blood stem cells,
and then testis stem cells, and, only more recently, the
amniotic-fluid stem cells. These are all fascinating and
important tools for research, but none of them are embryonic
stem cells.
Stem cells, in fact, I want to point out, is really a
category of cells, and the term ``stem cells'' is inexact. And
it's really more akin to the term ``seeds.'' We appreciate that
not all seeds are alike. An apple seed makes apple trees, an
orange seed makes orange seeds. And when we talk about apples
and oranges, we don't get them confused. Well, the distinctions
between seeds are essential to the biologist, just as the
distinctions among different stem cell types are essential. And
yet, in the public debate, I think, we lose the sense of
refinement about what different types of stem cells actually
are.
So, after many years of competing claims, embryonic stem
cells remain the most versatile stem cell, they remain the gold
standard of this fascinating biological concept of
pluripotency. And, after 20 years of research in the mouse, we
know that embryonic stem cells can make any cell type in the
body. Routinely, in my laboratory, we move from an embryonic
stem cell in a petri dish to an entire mouse within a month.
Those cells, we know, can make every cell type.
So, embryonic stem cells have unique properties, and they
will fulfill a unique purpose in research, a purpose that, I
would argue, will not be replaced by all of these other types
of stem cells. As was pointed out by Dr. Landis, human
embryonic stem cells are important tools for basic research. We
spend an enormous amount of time talking about their
therapeutic value. All of the different stem cell types will
have, we hope, 1 day, therapeutic value. But unique aspects of
embryonic stem cells pertain to their ability to model the
earliest steps of human development. If you really want to
understand the genetic regulation and the diseases that set in
during those first few days of human development, then studying
amniotic-fluid stem cells and fat stem cells will not get you
to those answers. Embryonic stem cells, therefore, are unique.
Now, it's often said, by opponents of embryonic stem cell
research, that embryonic stem cells have never yielded a
treatment, have never cured a patient. And that's true, but I
think it's a patently unfair criticism, because human embryonic
stem cells have only been around for 9 years. Actually, in the
last year, if you just look at the medical literature, human
embryonic stem cells have been used to generate a whole variety
of human cell types--blood cells, heart muscle cells, nerve
cells, and many, many more. So, they're beginning to yield
their fruits in basic research, and I think it's only a matter
of time before we see an impact on therapy. But to criticize
embryonic stem cell value for medical research is to trivialize
the enormous contribution of mouse ES cells for the past 20
years.
Scientists have generated literally thousands of strains of
knockout mice, which all derive from mouse embryonic stem
cells. And these have been used to model human cancer,
neurodegenerative disease. And, just a few years ago, there was
a publication that reported that knockout mouse strains
validate the targets of the hundred best selling drugs. So,
where it's true that human embryonic stem cells have not yet
yielded cures in the form of cell therapy, I think it's clear
that embryonic stem cells have already had a revolutionary
effect on biology, and they have saved lives--not directly,
through cell replacement, but indirectly, through insights into
disease and the development of drugs.
So, I want to close by saying that I believe there are no
credible scientific arguments which say that we should be
studying adult stem cells at the exclusion of embryonic stem
cells. And I'm looking forward to answering questions
pertaining to those issues. We must promote embryonic stem cell
research and adult stem cell research with equal vigor. And
Senate passage of S. 5 would be a very healthy start.
Thank you very much.
[The prepared statement of Dr. Daley follows:]
Prepared Statement of George Q. Daley, M.D., Ph.D.
My name is Dr. George Q. Daley and I'd like to begin by thanking
the members of the committee for inviting me here today. I believe
passionately in the scientific value of stem cell research, and I am
eager to present my views to the committee.
I am an Associate Professor at the Harvard Medical School based at
the Boston Children's Hospital. I am Associate Director of the
Children's Hospital Stem Cell Program and a founding member of the
Harvard Stem Cell Institute. I serve on the Public Policy committee of
the American Society for Cell Biology, which represents over 10,000
scientists, and I am President-Elect of the International Society for
Stem Cell Research, the world's leading organization of stem cell
scientists, which has grown to over 2,500 members in just over 4 years.
As a practicing physician-scientist, I run a busy research
laboratory at the Children's Hospital, where we study adult stem cells
of the blood--both their normal regulation and their pathology, as in
leukemia--and we study the formation of blood during embryonic
development. For this, we use embryonic stem cells. I also care for
adults and kids with malignant and genetic bone marrow conditions--
diseases like leukemia and lymphoma, immune deficiency, and sickle cell
anemia. Many of these diseases can be cured by bone marrow
transplantation--a form of stem cell therapy that harnesses the power
of adult blood stem cells, or as you will hear (or have heard) from Dr.
Wagner, from stem cells in Umbilical Cord Blood. While transplants are
effective for some, the reality is that marrow replacement represents a
heroic attempt at a life saving therapy for fatal diseases. The
transplantation regimen itself is highly toxic. I would not wish this
therapy on anyone who was not otherwise facing a potentially terminal
illness. As a direct response to these shortcomings of adult stem cell
therapies, my lab investigates the formation of blood stem cells from
embryonic stem cells, and is pursuing strategies for making rejection
proof, autologous tissues for transplantation. Our current treatments
for many blood diseases are stone age, and only through research can we
hope to make progress. I believe that embryonic stem cell research
holds the key to treating many blood diseases.
Stem cells come in many varieties. Even the term ``stem cell'' is a
very general term. It defines a generic category of cells that has many
members with different properties. It's about as specific as the
category ``seed.'' Seeds of all types share many properties, but an
apple seed makes apple trees and an orange seed makes oranges. When we
compare apples and oranges no one confuses the two. To a biologist, the
distinctions between seeds are crucial, as are the distinctions between
different types of stem cells. No credible biologist would argue that
one type of seed can teach you all you need to know about all seeds and
all fruit. Yet somehow, when we speak about stem cells in the current
debate, people tend not to appreciate the differences, and consider
them all interchangeable.
The media has covered a long list of ``breakthroughs'' that
purportedly represent new sources of stem cells that substitute for
embryonic stem cells. Initially, it was the Multipotential Adult
Progenitor Cell from Catherine Verfaillie's lab in Minnesota, later it
was the fat stem cell, then umbilical cord blood stem cells, and stem
cells from testes. Just last week we heard reports about stem cells
from amniotic fluid. All of these new types of stem cells are important
tools for research and may even one day yield new therapies. However,
none of them is the equivalent of embryonic stem cells. Perhaps they
can do some of the things that embryonic cells can do, but they cannot
do all of them. The differences between these other stem cells and
embryonic stem cells are very, very important.
We have also heard that there are alternative means of generating
embryonic stem cells without sacrificing embryos. There have been
exciting recent developments that claim ``reprogramming'' of adult
cells back to their primitive embryonic state, either by cell fusion
with existing embryonic stem cells, or by introducing a small number of
genes. Again, these achievements are noteworthy and fascinating, but
they have not yet produced cells that faithfully mimic or replace the
functions of true ES cells.
After many years of competing claims, ES cells remain the most
versatile of all stem cells. ES cells are the gold standard for the
biological concept of pluripotency, and it has been known from over 20
years of research in the mouse that ES cells can make all the cells of
the body. ES cells have unique properties and they fulfill a unique
purpose in biological research. Human ES cells are irreplaceable tools
for understanding the earliest stages of human development. They are
unique precisely because they come from the earliest human embryos--
before implantation into the womb, before even the most rudimentary
human form has begun to take shape. Understanding how these primitive
cells orchestrate the process of human development represents one of
the greatest goals of modern biology. Figuring out how amniotic stem
cells work or fat stem cells work will not teach us about the earliest
days of human development. Many different types of stem cells--adult
and embryonic--may prove useful for therapies. But embryonic stem cells
are the only stem cells that have been proven to form all cells in the
body, and this feature alone makes them worthy of study.
With regards to medicine, it is sometimes said by opponents of ES
cell research that ES cells have never cured anyone. This is a patently
unfair assertion because human ES cells have only been around for 9
years, and even now cannot be considered routinely available to
scientists in the United States. However, the detractors of ES cells
are naive in trivializing the contributions that ES cells have made to
biomedical research. Mouse ES cells have been used extensively to model
human disease and to study how gene variations influence cancer, heart
disease, neurodegeneration, metabolic disease, and many, many others.
Indeed, a paper published in 2003 reported that gene knock-out strains
of mice, which derive from ES cells, provided key target validation for
the effects of the 100 best selling drugs (Zambrowicz and Sands, Nature
Reviews, 2003). It is therefore fair to say that ES cells have already
saved lives--not directly through cell replacement therapies--but
indirectly through key insights into human disease and the development
of new drugs.
In closing, I want to stress that there is no credible scientific
argument that would justify studying only adult stem cells to the
exclusion of embryonic stem cells. Medical science does not advance
fastest by cutting off fruitful avenues of research that the
overwhelming majority of scientists and leading scientific societies
like the ASCB and the ISSCR believe are vital. We must promote
embryonic and adult stem cell research with equal vigor. We need a more
conducive Federal policy for human embryonic stem cell studies, and
Senate passage of Stem Cell Bill would be a healthy start. This vital
research should not be left up to the States to fund. We need to stop
making pseudo-scientific arguments against embryonic stem cell
research, and get on with the scientific challenges ahead.
Thank you.
The Chairman. Thank you very much, Dr. Daley. Very, very
helpful.
We have Lauren Stanford, here, a freshman at North Plymouth
High School. And we welcome her mother and father. I hear your
grandfather was William Ohrenberger, who was the superintendent
of schools in Boston, and a very enlightened and courageous
one, for many, many years, one of the great educators in
Boston, who also played professional football in the 1920s. He
was quite a guy. And Lauren follows in a very wonderful
tradition of public interest. She was good enough to write a
very moving letter, a year or so ago, when we were--had these
issues on the floor, and we've invited her back. We want to
welcome her parents.
This is the first day of school that she's been absent in I
don't know how many years. But, Lauren, we--you're among
friends here, and so, we hope you'll relax and, sort of, enjoy
it, too. It might not seem that way, but we want----
[Laughter.]
We want you to know that you're among friends, and you're
very welcome here. You've got a very, very, very important
message, and you've taken the time to give this a good deal of
thought, and we're very thankful for your being here.
STATEMENT OF LAUREN STANFORD, JUVENILE DIABETES PATIENT,
PLYMOUTH, MA
Ms. Stanford. Thank you.
I'd like to thank Senators Kennedy, Harkin, Specter, and
Enzi for inviting me to appear before your committees today.
It's wonderful to live in a Nation where the cares of a 15-
year-old girl from a small town are heard in the U.S. Senate,
and that is because of leaders like you. I admire and respect
all of you so much.
To see me sitting here, you'd think I'm just a normal
American teenager. And, in most ways, I am. I play tennis and
field hockey, I swim, and I ski. I'm pretty much addicted to
Instant Messaging.
[Laughter.]
I cannot survive without my cell phone nearby. Yes, on the
surface I'm just another American girl.
But inside me, a battle has been raging for 10 years now,
because, just after my 6th birthday, I was diagnosed with Type
1 diabetes. Type 1 isn't something you do wrong to get, it
isn't something you can change your habits to avoid. In the
past 10 years, diabetes has sent me to the hospital 14 times,
twice to intensive care; it has pricked my fingertips over
30,000 times; it has injected needles in me tens of thousands
of times; and it has forced me to learn to change my own pump
catheter every 2 days, from the time I was just 7 years old. It
has forced my mother to be a part of my life in a constant way,
every hour of every day. Now, imagine accepting that, as a 15-
year-old girl.
Diabetes has, indeed, ruled every minute of my life. Every
2 months, doctors peer deep into my eyes waiting for the time
when they can tell me it's begun to break down my eyesight.
They poke at my feet and my hands to see if it's robbed me of
my circulation yet. They test my kidneys to see how far its
assault on them has gone. And through all of this, I walk and
talk and try to live in the world as just another American
girl.
But time is not on my side, and I know that my only hope
for a cure lies in medical research. My parents--my family has
helped me learn about research over the years. And my friends
and I have raised a lot of money to help fund it. My group,
called ``Got Islets: Lauren's League for a Cure,'' has raised
hundreds of thousands of dollars for the Juvenile Diabetes
Research Foundation since I was diagnosed, and we are just a
bunch of kids. But we kids can't do it alone. We need the
Government to help by allowing scientists to fully unleash the
potential of embryonic stem cell research. This research could
hold the key to a change in, not just my life, but in the life
of so many Americans.
Imagine if it can help get to the source of what causes
diabetes and stop it before it starts. Imagine if it can find a
way to create new islet cells so my destroyed ones can be
replaced with working ones. I cannot imagine what it's like to
have 1 day--just 1 day when I was not sick. That's because I've
had diabetes for longer than I can remember. Now is the time to
expand the current stem cell research policy, not just because
I want to know firsthand what a healthy day feels like, but
because scientists believe they can make real advances in the
search for cures for diabetes and for other diseases, as well.
While I wait for scientific advances, I really am doing all
I can to help keep myself alive. Recently, I took a brave new
step in fighting diabetes, and it has not been easy. I am now
wearing what is called the Continuous Glucose Monitoring
System, and I'm one of the first kids in the Nation to do it.
This means I have a radio transmitter strapped to my side 24/7,
in addition to my insulin pump. Attached to it is a wire probe
that I insert under my skin every few days--again, on my own,
doing something most would need medical staff for. It helps me
see, more often, what my blood sugar is, and it helps me keep
my blood sugar in better control. But it's not a cure. It's a
step forward in helping me take better care of myself until
scientists find a cure, because, even though I have more
information from it, it's not stopping diabetes from attacking
my body.
I still get high and low. I still need insulin. I still
fear the future, because, you see, I have hopes and dreams for
a future, like most other kids. I want to go to a great
college, but I have to worry about how to balance my constant
care with life in the dorms. I want to get married and have
children, but I have to worry about: How will I make that
happen? Women with diabetes can have children now, but only
with a constant and very invasive care. I want to be a Senator,
like you, but I have to worry if my body will hold up long
enough to help me get the experience I need to even try for
that.
I have to admit, I am lucky in some ways. Living in
Massachusetts and near Boston means I am very close to some of
the best care in the world. At my diabetes camp and through my
advocacy, I've met kids who are not that lucky. They don't have
a good team to help them take care of themselves and try new
treatments, they don't meet with great researchers like we have
at Harvard. I worry for them, too. How will they achieve their
dreams if I'm worried about mine?
I'm also very lucky that my parents are willing and able to
work very hard to pay for all the things that diabetes demands,
because, even with good insurance, it's expensive. Pump
supplies, needles, insulin, test strips, and more, it all adds
up to tens of thousands of dollars my parents spend. What about
the kids who are not lucky enough to afford that?
Embryotic stem cell research could be a key answer to all
of this. As I try my hardest to take the best care of myself I
can, and those thousands of kids out there who are not as lucky
as me do best in their situations, I hope that the Government
will do its part by giving our best scientists the best tools
to get a cure as soon as possible.
One of the best tools out there is definitely embryonic
stem cell research. With it, with our great Nation and
brilliant scientists, I can go on and live the life that I
dream of. Will I go to a good college? Maybe. Will I get
married and have kids? Hopefully. Will I be a Senator? We shall
see. But one thing is for sure--once stem cell research helps
us cure diabetes, I'll be that one thing I truly dream of
being: just another American girl.
The Chairman. Very good, Lauren.
[Applause.]
Very well done.
John Wagner, professor of pediatrics, University of
Minnesota, we welcome your testimony.
STATEMENT OF JOHN E. WAGNER, JR., M.D., PROFESSOR OF
PEDIATRICS, UNIVERSITY OF MINNESOTA MEDICAL SCHOOL,
MINNEAPOLIS, MN
Dr. Wagner. Thank you, Senator Kennedy, Senator Enzi,
Senator Specter----
The Chairman. Push the button. Push the button.
Dr. Wagner [continuing]. Thank you for allowing me to speak
today. As was said, my name is John Wagner. I'm a professor of
pediatrics. I'm a co-director of the Stem Cell Institute at our
institution, as well as the head of the Bone Marrow Transplant
Program.
Over the past decade, there have been several major events.
One is breaking down the genetic code, and the second is stem
cell therapy. I take care of patients with incurable diseases,
and I'm here to represent many of those patients, who are
looking for cures, whether it be spinal cord injury, diabetes,
Parkinson's, whatever the disease.
We're looking for new strategies that give them hope, and,
as others have already said, I think we're on the cusp of
seeing this become a reality. But I'm also here as a staunch
advocate of adult stem cells. Clearly, there is a role for
adult stem cells. We've seen a great deal of promise in all the
publications that have been coming out over the past couple of
years. These clearly need to be explored. But it needs to also
be unequivocally clear that there is only one proven cure,
that's been documented, with stem cell therapies from adult or
neonatal tissues, and that's in the setting of bone marrow
transplantation for the treatment of leukemia, lymphoma, sickle
cell disease, immune deficiency. Clearly, what we're doing
there is, we're replacing diseased bone marrow with bone-marrow
stem cells or cord-blood-derived stem cells. Now, that's the
only proven cure. And as Dr. Daley said, you know, ``Well, what
have you shown us, in terms of cures, with embryonic stem
cells?'' Well, clearly lots of work needs to be done, both with
embryonic stem cells, but with adult stem cells, as well.
Many different trials are being conducted right now looking
at the use of adult stem cells in the treatment of heart
disease, in the treatment of spinal cord injury, bone
disorders, genetic diseases. Clearly, they need to be explored.
But have we proven any success yet? No, we haven't. But I think
that we need to also step back for a second, because I'm a
clinical trialist, I'm the one who actually designs new
therapies and tries them out for the first time. Some of the
families of my patients are actually right here, because
they've actually tried brand new things, because there is no
cure for their underlying disease. So, we try new things, and
it doesn't always work.
I think that there are a few obstacles and a few things
about moving this field forward. One, is that--What are
realistic expectations? When we do stem cell therapies, whether
it be adult stem cells, as we're doing very much today, or
embryonic stem cells, perhaps in the future, you don't expect
home runs to occur the first time you test them out.
Let me give you one example. What I did, and what I am a
pioneer in, is the use of umbilical-cord blood as a source of
stem cells for treating patients with leukemia. If you go back
and look where we were in 1990, when I performed the first
cord-blood transplant for a child with leukemia in the world,
the patient didn't survive. Did we give up? No, we continued.
And, just a year ago, there--with the Stem Cell Act, we were
able to actually markedly expand the collection and storage of
umbilical-cord blood. And why did we do that? It's because
we've actually been able to show, now, through our work at the
University of Minnesota, that others are now replicating--we've
tripled the survival in adult patients with leukemia and
lymphoma. We've now been able to improve upon the overall
survival rates with children. And we now are able to address
the concerns of access to stem cell therapies to patients of
ethnic and minority descent. We can find donors for almost
everyone, which we could not previously do. So, we've made
substantial progress, despite the fact that the first trials
were failures.
There are other obstacles, however, that you have to keep
in mind. One of the things that's touted as a benefit of adult
stem cells, which is probably still a benefit of adult stem
cells, is the fact that there could be tissue matching. I could
collect stem cells from every one of you in this room and
actually be able to create a multipotent adult stem cell that
we could actually then re-infuse into your diseased heart or
whatever the organ that needs to be fixed. Now, one thing we've
also learned is that the immune system, unfortunately, attacks
those cells, as well, even if it's from your own body. There's
something peculiar about the stem cell
that we have to address. The fact that it's matched, the fact
that it's from your own body, doesn't mean that it won't be
immune-
rejected.
Well, what we've also learned is strategies to make this
work. And, in fact, over the next year, I hope I can say to you
that we will have done the first trials with the multipotent
adult stem cell that was discovered in our institution by Cath
Verfaillie. It will then be tested in patients who are
undergoing chemotherapy and radiation, as a way of tissue
repair. The advantage of that setting is because of the fact
that these patients will also be immune-suppressed and
hopefully given the chance, the best chance, for these stem
cells to engraft, to divide, to replicate, and to repair
tissue.
But what happens if it doesn't work? Do we give up? No, we
continue. And, in fact, probably the first trials won't work.
The first trials are actually a safety study. But this will be
one of many generations of trials. Just like with cord blood,
16 years ago, when we did that first transplant, this will be
an evolutionary process.
The last thing, because one of the tasks today was--I was
asked, Can Congress help fulfill the promise of stem cell
research? And this goes back to Dr. Landis, is the fact that--
you know, where are we, in terms of NIH dollars? We are still
inhibited by--we have our hands tied by the amount of funding
that's available for this research. And, in fact, although I am
an example of a successful candidate for getting research for
clinical trials, unfortunately not a single trial has been
designed by me, at least in the past, that has been substantial
enough to be able to pay for the clinical trial itself. It
requires multiple sources of funding for every clinical trial
that we do, or I have to design the trial such that it's a
small trial that can be within the confines of what the NIH
will allow me in their cap.
But if we want to move these cell therapies forward, we
have to invest in them, we have to recognize the obstacles, you
have to understand the translational pipeline and its current
problems. And how do we make this work? We have the tools to do
that, and we're here to help you, if you want us to.
But every single one of us, in conclusion, will be faced
with a disease that will be amenable to stem cell therapy. It
might be our child, it might be our spouse, it could be us.
Adult stem cells and cord-blood stem cells have benefits in the
treatment of blood cancers. We know that. What we have to do is
to be able to explore other diseases outside the context of
bone marrow transplantation. It's essential that Federal funds
be devoted to this. I think that you support it. We have to
make it move forward, but also have real expectations. We do
this for ourselves, for the science, but, most importantly, for
the children and our families.
Thank you.
[The prepared statement of Dr. Wagner follows:]
Prepared Statement of Professor John E. Wagner, Jr., M.D.
EXECUTIVE SUMMARY
Over the past decade, two major events promise to revolutionize the
practice of medicine--unraveling the genetic code and the isolation of
the stem cell. Today, there is only one proven use of adult stem cells
and that is in the context of blood and marrow transplantation to treat
diseases such as leukemia, lymphoma, sickle cell disease and various
other blood and immune disorders.
Accomplishments using stem cells from adult and neonatal tissues
include: (1) our demonstration of their capacity to differentiate into
cells of multiple tissues, (2) their safety and efficacy in laboratory
models of disease, and (3) procedures for manufacturing stem cells for
human testing.
There are many new adult stem cell projects moving to clinical
trials. It is unrealistic to expect that there will be home runs; and,
it may take several generations of studies to make a new therapy work.
The Stem Cell Therapeutic and Research Act of 2005 authorized
substantial funds to be used to increase the Nation's inventory of cord
blood by 150,000 units. The NCI and NHLBI are supporting multi-
institutional trials in children and adults to validate these results
pioneered at the University of Minnesota. This is an example of what
your support has accomplished and what it takes to move stem cell
therapeutics from concept to clinical testing to standard of care.
We are now ready to test the multipotent adult stem cell, the cells
discovered by Dr. Verfaillie and colleagues. But, importantly we have
also identified obstacles, reasons why these may fail to repair injured
tissues. While it is touted as one more advantage of adult stem cells
over ES cells, it is now clear that the most primitive adult stem
cells, even those directly from the patient, are susceptible to immune
attack. This serves as a clear example of why it is not enough to show
that a cell can differentiate into a tissue, the right models need to
be used to predict clinical outcome.
Gap funding for Phase I clinical trials is an obstacle to our
success. Currently, the Federal grants are too small to complete the
trials and we must compile several funding sources to move forward.
There are things we can do now that will speed the process of
moving new laboratory discoveries to clinical trials. First, you need
to understand the translational pipeline, its components, how it is
funded, and the potential obstacles. Second, it is necessary to
understand why there are disincentives for clinicians and basic
scientists to engage in this translational research--as this will help
identify solutions. Third, and perhaps most important, you must be able
to differentiate speculation from fact, as it pertains to stem cells,
as there is a considerable misinformation and misunderstanding out
there on what adult stem cells can and cannot do.
______
Senator Kennedy, Senator Harkin, Senator Enzi, and Senator Spector,
thank you for the opportunity to speak today. My name is John Wagner. I
am the Director of Hematology/Oncology and Blood and Marrow
Transplantation Program and Scientific Director of Clinical Research
for the Stem Cell Institute at the University of Minnesota.
Over the past decade, two major events promise to revolutionize the
practice of medicine--unraveling the genetic code and the isolation of
the stem cell. The rate that new genes are discovered and their
function understood have been extraordinary. Take for example, BRCA2--
the breast cancer gene. In my own clinic in the treatment of children
with rare life threatening disorders, we have learned that this genetic
defect is not only associated with breast and ovarian cancer in adults
but also leukemia, brain tumors and kidney tumors in very young
children. In fact, detection of this genetic defect in young children
has allowed me to predict with high certainty what cancers will develop
and when. This is powerful information because it has allowed me the
opportunity to pre-emptively intervene and alter the future predicted
by these genes. One intervention has been the use of stem cells.
Today, there is only one proven use of adult stem cells and that is
in the context of blood and marrow transplantation to treat diseases
such as leukemia, lymphoma, sickle cell disease and various other blood
and immune disorders. This has been known for 40 years. For these
diseases, we infuse stem cells to repair marrow that has either been
destroyed by the disease itself or by treatments, such as high doses of
chemotherapy and radiation. These blood producing stem cells come from
adult marrow or cord blood (the blood left in the placenta after a baby
is born).
A year and a half ago I presented before Senators Harkin and
Spector to defend the vital importance of embryonic stem cell research.
While I unequivocally support embryonic stem cell research, it must
also be clear that adult stem cells have an important place in medicine
as well. While adult stem cells do not replace the need for ES cells,
they will likely complement it.
The principal accomplishments over the past 5 years using stem
cells from adult and neonatal tissues (such as cord blood, amniotic
fluid and the cord itself) include: (1) our demonstration of their
capacity to differentiate into cells of multiple tissues (e.g.,
mesenchymal cells into neurons; cord blood stem cells into cells of the
lung), (2) their safety and efficacy in laboratory models of disease,
and (3) procedures for manufacturing stem cells for human testing. In
fact, the first clinical trials have already been initiated in acute
heart disease (heart attacks) and chronic heart failure, acute brain
injury and lung injury. In addition, clinical trials with organ-
specific stem cells are already being studied in diabetes in addition
to those in bone marrow transplantation.
With National Institute of Health (NIH) research dollars and other
governmental and nongovernmental support as well as philanthropic
support, there are many new projects moving to clinical trials. At our
own laboratory, we are collaborating with investigators at Johns
Hopkins, helping to develop clinical manufacturing methods for testing
cardiac stem cells; we are collaborating with investigators at Tulane,
developing stem cell populations for treatment of genetic disease and
bone repair; and, we are working with industry, such as Athersys,
manufacturing multipotent adult stem cells for treatment of radiation
and chemotherapy injury. Significant progress has been made.
It is unrealistic to expect that there will be home runs; and, it
may take several generations of studies to make a new therapy work. As
an example, cord blood used to treat leukemia and lymphoma took years
before it reached its current success. In 1990, I performed the first
cord blood transplant in the world for a child with leukemia. While
this child unfortunately died of his underlying disease, scientifically
it was a success--thereby giving us a reason to push forward. Eight
clinical trials later, we made modifications that have led to
extraordinary survival rates in adults with leukemia. Now, patients
from all over the world are now receiving this therapy. In addition,
the ``double cord blood'' platform, has solved the problem of access--
permitting us to find donors for more than 80 percent of patients,
particularly important for patients of ethnic and racial minority
descent.
The Stem Cell Therapeutic and Research Act of 2005 authorized
substantial funds to be used to increase the Nation's inventory of cord
blood by 150,000 units. The NCI and NHLBI are supporting multi-
institutional trials in children and adults to validate these results
pioneered at the University of Minnesota. This serves as just one
example of what your support has accomplished and what it takes to move
stem cell therapeutics from concept to clinical testing to standard of
care.
After 5 years of intense study, we are now ready to test the
multipotent adult stem cell, the cells discovered by Dr. Verfaillie and
colleagues. We are about to submit our first application to the U.S.
Food and Drug Administration. Over the past 2 years, we have compiled
safety and efficacy data in laboratory models and developed the
procedures for reliably producing these cells for individual patients.
The first trials will take place in the setting of radiation and
chemotherapy injury and the goal is to demonstrate safety and hopefully
signs of tissue repair. Will it cure patients--may be not. Do we give
up--no. As in the early trials with cord blood, we have to carefully
design the right studies that will insure that we learn why the cells
work or why they don't work should that occur. We already know in
laboratory models that multipotent adult stem cells will home
preferentially to areas of tissue injury.
But, importantly we have also identified obstacles, reasons why
these may fail to repair injured tissues. While it is touted as one
more advantage of adult stem cells over ES cells, it is now clear that
the most primitive adult stem cells, even those directly from the
patient, are susceptible to immune attack. This serves as a clear
example of why it is not enough to show that a cell can differentiate
into a tissue, the right models need to be used to predict clinical
outcome. For this reason, our first trial with the multipotent adult
stem cell will be in immune suppressed patients with tissue injury,
giving every chance for these stem cells to engraft into damaged
tissues and effect tissue repair.
It is not enough to give hope based on the results from a Petri
dish. We must have better models to move the science forward. It is
exactly this stage of research that is sorely lacking in funding--this
in between stage. Gap funding for Phase I clinical trials is an
obstacle to our success. Currently, the Federal grants are too small to
complete the trials and we must compile several funding sources to move
forward.
It is not a question of whether this new knowledge will
``translate'' into a useful clinical treatment but rather--when? I
receive hundreds of emails and letters monthly asking for direction,
help and above all--hope. As a physician who sees patients for whom
there is no known treatment, I explore the unknown. I have to keep
trying. For the most part, I have made some good decisions and patients
have benefits. While it will never be fast enough, there are things we
can do now that will speed the process of moving new laboratory
discoveries to clinical trials. First, you need to understand the
translational pipeline, its components, how it is funded, and the
potential obstacles. Second, it is necessary to understand why there
are disincentives for clinicians and basic scientists to engage in this
translational research--as this will help identify solutions. Third,
and perhaps most important, you must be able to differentiate
speculation from fact, as it pertains to stem cells, as there is a
considerable misinformation and misunderstanding out there on what
adult stem cells can and cannot do.
It must be clear that no study with adult or cord blood stem cells
outside the context of bone marrow transplantation has proven efficacy.
While there are claims to suggest otherwise, the results are either
contradictory or too preliminary. While I wish that I could tell you
otherwise, speculation seems to get confused with fact. While
promising, adult stem cells do not exhibit all the capacities of ES
cells. For example, we have yet to see stem cells from cord blood or
adult tissues (outside the heart) differentiate into heart muscle cells
that spontaneous beat, as has been shown repeatedly with ES cells.
Can Congress Help Fulfill the Promise of Stem Cell Research?--
Absolutely. We are here today to help you understand what we know, what
we think we know and how you might help translate this hope of stem
cells into reality. In addition, it is important to know exactly how
much is currently being spent on stem cell research. This involves
separating how much is spent on adult/cord blood versus ES stem cells
and separating adult/cord blood stem cells into hematopoietic (bone
marrow transplant) and nonhematopoietic. In my opinion, this is not
clear to the public.
Every single one of us will be faced with a disease amenable to
stem cell therapy. It may be our child, our spouse, our friend or even
ourselves. Adult and cord blood stem cells have proven benefits in the
treatment of blood cancers and other disorders and perhaps even in
tissue repair that has yet to be clearly proven. It is essential that
Federal funding be devoted to stem cell biology and therapeutics. All
the required components to make this work already exist--we just need
to bring them together. There are patients in this room today and
parents of children who have passed away looking for a chance to see
this hope move into a reality. The results are extraordinary; we have
to make it happen now on their behalf. For them, the stakes are
unimaginable.
The Chairman. Well, thank you. Thank you very much. Very
good panel.
We've got 12 members here. I thought we'd just do 4
minutes, so everybody gets--tries, basically, a question and a
followup. That's still 48 minutes, but at least we'll give
everybody, hopefully, an opportunity. And then, for those that
want to--are able to remain, and our panel remain, then we'll
stay here afterwards, but permit everyone.
I'd like to ask, Dr. Landis, Do you believe that
restricting the NIH funding to the small number of cell lines
included in the current policy allows the federally funded
scientists to explore the full healing potential of a
remarkable new field? Are we missing out on possible
breakthroughs under the current policy?
Ms. Landis. Yes, we are missing out on possible
breakthroughs. From a purely scientific perspective, Federal
funding of additional cell lines is necessary to advance the
field. The cell lines that are eligible for NIH funding now
have been shown to have genetic instabilities; in particular,
with respect to epigenetic changes in methylation. NIH--
scientists who are funded by NIH would also like to have access
to cell lines that have been derived without the use of feeder
cell lines or animal products. And, finally, there are a number
of cell lines--many cell lines that have been generated since
the President's policy was put in place that have in them
mutations specific to human diseases, like Huntington's and ALS
and Parkinson's. That would be extraordinarily useful for
learning about the progression of disease and testing drugs,
and those are not available either. So, yes, more cell lines
would be incredibly important.
The Chairman. Dr. Daley, what happens to the best of the
American researchers--give us--with the current policy? Where--
has this research been going abroad? Tell us what's happening
to the young, ablest, most gifted researchers. Will they get
into this field, or are----
Dr. Daley. Yeah.
The Chairman [continuing]. Or are they going into other
areas?
Dr. Daley. Yeah, you know, we, in the United States, enjoy
a remarkable luxury of support from the Federal Government for
our research. And because we have, I think, some of the best
research infrastructure, the best universities, we tend to
attract the top young scientists from all over the world.
Increasingly, though, when I interview researchers from Europe
or from Asia, they ask whether or not there is a supportive
enough environment in the United States that they should commit
their careers to coming to the United States to do embryonic
stem cell research. I can't say--or give you a number of the
ones who decide against coming. The ones who do come to my lab
are those intrepid few who are so caught up in the excitement
of the science--and I say there are a remarkable number of
scientists internationally who are voting with their feet to
study these cells, they are fascinating cells. But I have every
sense, every belief, that there are people who are being
dissuaded from this very interesting new area of science
because of the political climate here in the United States.
The Chairman. Lauren, a young lady of courage and
fearlessness, if you had the President here today, what do you
think you'd tell him to encourage him to support this program?
Ms. Stanford. I think I'd probably just tell him about the
struggles that I've gone through and about how passing this
bill would be very important to me and all the other people
with diabetes around the world, and it would be a big help if
he just didn't veto the bill.
The Chairman. Very good to hear.
My time is up.
Senator Enzi.
Senator Enzi. Thank you, Mr. Chairman.
I recognize the message that everyone's given, that more
money needs to be spent on all kinds of stem cell research. And
I don't think there's, probably, anybody that disagrees that if
there was more spent, there would be more discoveries, and we'd
know more. One of the difficulties is allocating more money to
some things, when we're requested to do it for everything. We
have to recognize that there is a significant group of people
out there that feel that embryonic stem cell research would be
very similar to the other end of the spectrum, where people
might go through nursing homes and find people who no longer
can talk, probably close to death, they're just going to be
thrown away, and perhaps they could be used for research, but
not with their permission. That group of people will object to
spending taxpayers' dollars on similar procedures for embryonic
research.
The more people that agree that there are moral ways to do
this, the more support there'll be for it. I want to
congratulate Senator Isakson for the work that he's done to try
and come up with some compromises and expand the capability of
research. A bill that, I think, has the capability of bringing
more money into the system.
Professor Wagner, I want to thank you for coming, and I
want to thank the patients that joined with you today, as well.
It does sound like you're making great progress with the adult
stem cell research. I know that you recognize embryonic stem
cell research is important, as well. But do you think an
expansion of adult stem cell research will lead to more
therapies in the next 10 years, perhaps more quickly than
embryonic stem cell research? Realistically, are there any
particular treatments, other than the ones you're working on,
that you're intrigued by and excited about seeing put into the
clinical setting?
Dr. Wagner. Well, Senator Enzi, I mean, first off, you
know, as you stated, I mean, I think that we should be
exploring both embryonic stem cell research, as well as adult
stem cell research. Clearly, more money in adult stem cell
research will obviously help us advance that, perhaps more
quickly, because of the very fact that there's less money for
embryonic. On the other hand, with that said, it clearly is a
supporter for both, but yet, adult stem cell work is now being
explored not only for, you know, correcting bone disease, liver
disease, lung disease, it's also now being explored for a way
of treating patients with diabetes, as well.
But we're at the very earliest phases. The fact is, that
it's still quite speculative. You know, I'm not saying that it
will ever achieve the same status as an embryonic stem-cell-
derived therapy, but clearly we need to explore all the
options, and everything is wide open. Many people are working
on all these areas simultaneously.
Senator Enzi. Very quickly, Dr. Landis, we're operating
under CR now, which limits the amount of money. There's no
expansion of money. Were we to end the embryonic stem cell
Federal funding prohibition, what research would you cut in
order to get the research done on that?
Ms. Landis. That's a very challenging question that we're
facing every day at my Institute. If we do this, what won't we
do? What NIH does, in general, is to not set aside specific
pots of money for particular projects, but to fund the very
best science. And, as we've heard, some of the very best
scientists are incredibly excited about human embryonic stem
cells, and expansion of the lines would enable them to write
wonderful applications, which we would review and hopefully
have the money to fund.
Senator Enzi. Thank you.
And my time is expired.
The Chairman. Senator Harkin.
Senator Harkin. Thank you, Mr. Chairman.
I just want to respond a little bit to what was just said.
You know, this image is always brought up of old people, as if
we're going to use them for experimentation and stuff. Let's
just keep in mind what we're talking about here. We're talking
about a blastocyst with about 150 cells, has absolutely no
human form whatsoever. Does it contain all the genetic material
and stuff? Yes, it does, just like a sperm and an egg does.
That's what we're talking about here.
So, I listened to the debate that was on the House floor
last year on this, and one speaker got up and talked about
destroying fetuses. This is the kind of misinformation that
gets out all over America, that we're going to destroy a fetus.
And they said it clearly on the House floor, that that's what
this was about. So, you know we've got to continually combat
this kind of misrepresentation of what we're talking about
here.
One other thing we have to clear up is the fact that the
Federal Government is already spending U.S. Federal tax dollars
on embryonic stem cell research. We already are, on 21 outdated
contaminated lines that were derived prior to 9 p.m., August 9,
2001. So, don't tell me that we can't spend U.S. Federal
taxpayers' dollars on stem cell research. We're already doing
it. The fact is, we're only doing it on those that were derived
prior to 9 p.m., August 9, 2001. Somehow, that's moral. But to
do it on those derived after August 9, 2001, 9 p.m., is
immoral. I don't know why that is a dividing line of morality.
I've often asked, ``Why wasn't it 9:05 p.m., 9:30 p.m.?''
``Midnight, 8 p.m.'' Why was it 9 p.m., August 9, 2001, that
somehow is the dividing line?
Well, when that happened, I said, we thought 70-some lines
were available--I thought that might be enough. But now we know
it's only 21, and every one's been contaminated and will
probably never lead to any kind of human therapies. So, we have
to keep in mind that we already are spending taxpayer dollars
on embryonic stem cell research. All we're asking is, let's
expand that, and let's get new lines, that are not
contaminated, some that are healthy and vibrant, that have been
derived already by private sources. That's what we're talking
about. So, I continue to try to clear this up, to point out
that NIH funds are already available for this.
Now, I was just figuring out the budget here, Dr. Landis.
Last year, about 2 percent--my figure--of the entire NIH budget
went for all forms of stem cell research--adult, animal
embryonic, animal nonembryonic, all of it. It was about 2
percent.
I just think that that is woefully inadequate. And I just
won't buy this argument that somehow we're so limited by the
budget that we can't do this, when we're spending $8 billion a
month on the war in Iraq. Eight billion a month? And we're
spending $637 million, last year, total, on all stem cell
research? Don't tell me the budget's limiting us. It's the
priorities we have as a Nation, and it's the priorities we set
as a Senate and a House, that determines how much we spend.
There's no magic thing out there that says you can't spend more
than this on research.
Well, I've used up my time, and I didn't even get to ask a
question, but there is one I just want to ask.
[Laughter.]
Dr. Daley, I wanted to ask you this. Some people say we
don't need more Federal support of embryonic stem cell research
because States and private resources are funding it.
California's jumped in. Wisconsin's jumped in. New York's
jumped in. I don't know if Massachusetts has.
Dr. Daley. Not yet, but I hope so.
Senator Harkin. Well, okay. So, maybe we don't need more
Federal funding. Let the States do it.
Dr. Daley. No, actually, this is not an issue for the
States. I mean, who's to say that the breakthroughs are going
to come in California or New Jersey? And I have outstanding
colleagues who are in other States--Michigan, Arkansas, Iowa.
Those researchers in those States should be allowed to obtain
Federal funding. This is a Federal issue. The Federal
Government is the lifeblood of scientific research. Virtually
all of my funding comes through the Federal Government. It's a
reliable source, it's subject to peer review, it's subject to
ethical oversight. It's very hard to raise private money, and
it's taken outside of those oversight processes when it's--when
the research is done privately.
Senator Harkin. Thank you, Doctor.
Thank you, Mr. Chairman.
The Chairman. Thank you. Thank you very much.
Senator Specter.
Senator Specter. Thank you, Mr. Chairman.
Thank you very much for coming in, Ms. Stanford. I'm very
interested to hear your desire to become a U.S. Senator.
[Laughter.]
You're 15, you'll be eligible to run in 15 years. I just
want to offer a word of caution, that Senator Kennedy will
still have a decade left----
[Laughter.]
Under Senator Thurmond's tenure.
[Laughter.]
So, be patient.
[Laughter.]
Lauren, when we have these hearings we wonder what their
impact is. Speaking, perhaps, for many people in your
situation, does this hearing give you more hope? Does it
encourage you that something really may be done to deal with
your diabetes problem?
Ms. Stanford. Well, just coming here and talking, I know
that my voice is being heard, and that gives me a lot of hope
that something may happen in the future and I may have impacted
someone's opinion on something else or a choice to make, and it
makes me feel good about myself and good about the future.
Senator Specter. Dr. Wagner, you testified that you infuse
stem cells into the heart or other organs which need to be
repaired. Could you be specific as to what prospects there
are--I know it's subject to experimentation, but what prospects
there are to deal with Lauren Stanford's diabetes, or what the
prospects are to deal with Arlen Specter's Hodgkins disease?
Dr. Wagner. Well, you've asked quite a few questions right
there. I mean, but in terms of the prospects for----
Senator Specter. I've only got 4 minutes.
[Laughter.]
Dr. Wagner. Well, clearly, the one we know is actually
Arlen Specter's cancer, because if it's a lymphoma, then
clearly we have tried-and-true therapies, though I don't know
the details. But, on the other hand, we have--we do have
therapeutic--proven results in patients with lymphoma leukemia.
The question then is, is that--Where do we go outside the
context of the classic bone marrow transplantation, such as in
diabetes or in heart disease? What I can specifically address
right now is that there are a number of studies, both at our
institution and others, where we're specifically taking stem
cell populations, whether it be cardiac stem-cell-derived, or
whether it be mesenchymal stem-cell-derived, and actually
inputting them into patients with heart failure. Have we proven
benefit? The results are mixed. But this--again, this is a step
one. But we are moving these cell therapies into clinical
testing. It will be only time before we know the true benefit
in that speculation, at this point.
Senator Specter. Dr. Daley, this is your fourth appearance
before this subcommittee--in 2002, in 2005, in 2006. Are you
getting a little tired of coming here without better results?
Can you be a little more persuasive on this thing?
Dr. Daley. Yes, I----
[Laughter.]
Well, I have to say that I think it's been a bit
frustrating that the political--or the--let me say it
directly--I think the politicians have been lagging somewhat
behind the American public. We've been out there, as a
scientific community, trying to speak out on these issues,
trying to educate, trying to justify the importance of stem
cell research.
Senator Specter. Dr. Daley, let me interrupt you----
Dr. Daley. And----
Senator Specter [continuing]. Because I've only got a few
seconds left, and I want to ask Dr. Landis a question.
You are the vice chair of the NIH Stem Cell Task Force?
Ms. Landis. Yes.
Senator Specter. The subcommittee has polled all of the
institutes, and it's gotten responses almost everywhere,
``Please give us embryonic stem cells.'' The question is
raised, Where are you going to get the money? As a matter of
priorities, isn't it true that many of the institutes would put
embryonic stem cell research at a higher priority and make some
funding available?
Ms. Landis. Yes, we absolutely would. In fact, in NINDS we
have several program announcements with setasides specifically
for enhancing the likelihood of investigators working in this
area that they would get funded.
Senator Specter. Thank you, Mr. Chairman.
The Chairman. Thank you.
Senator Brown.
Senator Brown. Thank you, Mr. Chairman. And thank you for
calling this hearing, the joint hearing.
I am----
The Chairman. I have Senator Brown, Coburn, Lautenberg, and
Isakson. If there's a difference in that, or someone has a
particular schedule, if they want to just have their staff let
us know, and we'll try.
Thank you.
Senator Brown. Thank you.
I sat on the House Subcommittee on Health for many years
and it's heard several hearings on this whole issue of
embryonic stem cell research. Of all the issues we discuss in
healthcare and in other issues in the Senate and in the House
when I was there, few issues seem so clear cut to me as this
one. From all the substantive questions, we talk about how the
position of our Federal Government on embryonic stem cell is
almost for sure causing some very young--for some young, very
bright scientists to look elsewhere. We lose that potential.
Some evidence of some scientists going overseas to Singapore,
others--perhaps overstated, but some evidence of that. I hear
Senator Harkin and then Dr. Landis repeating the four-door
metaphor, if you will. All this is--as I said, of all the
issues that come in front of this committee and other
committees, this one seems so clear cut to me, and it's so
discouraging, having just gone through a campaign talking about
this issue and seeing overwhelming public support for it, that
we can't get further along than we have.
Dr. Daley, would you give us some very specific,
understandable-to-the-public, recent breakthroughs or about-to-
happen breakthroughs that can help us along with this, to go
home and talk about in continuing to educate the public, who
will then continue to educate the President and other
policymakers about the importance of stem cell, if you would.
Dr. Daley. Yeah, I would point to the papers, just in the
last year, that have highlighted the formation of specific
cells from human embryonic stem cells. It's the beginning. You
know, are they breakthroughs? This is the hard work of basic
science. But the fact that you can make human skin cells,
tendon cells, bone cells, liver cells, muscle cells,
dopaminergic neurons, motor neurons--I have a list here. This
is a graph that shows the publications, by year, for different
stem cells. Look at the inflection point here. It's just
growing exponentially, the number of publications around
embryonic stem cells. And there are breakthroughs among them. I
would point to any number of diseases where understanding the
cellular basis is really advanced by these types of
publications.
Senator Brown. Thank you.
Thank you, Mr. Chairman.
The Chairman. Senator Coburn.
Senator Coburn. Thank you. Senator Kennedy, if I might, I
might yield to Senator Isakson. I believe he has a plane to
catch.
The Chairman. Fine.
Senator Isakson. Good, absolutely. Thanks, Senator Coburn.
First of all, I thank all the--I thank the Chairman for
calling the hearing today, and all the other chairmen and
ranking mem-
bers----
[Laughter.]
Their testimony. I don't want to make any of them mad. And
thank all the panelists. Lauren, you were terrific. I'm glad
you are in Massachusetts and Senator Kennedy has to worry about
you.
[Laughter.]
If you move to Georgia, I'm in big trouble, and I know
that.
[Laughter.]
And I have to say, personally, to Dr. Wagner, on a personal
note, my sister's life was saved because of bone marrow
transplant therapy that was developed in the 1990s and tried at
the University of Nebraska Medical Center in Omaha, where I
spent 3 weeks staying with her when that happened. So, I'm very
grateful for the work that you do, and the advancement of the
work that you do.
Dr. Landis, it's my understanding that one of the benefits
of any NIH investment is, it takes the information that is
gained from the research and puts it in the public domain;
whereas, if it's done strictly privately or overseas, that
information remains proprietary. Is that correct?
Ms. Landis. So--there are differences in publication
strategies used by people funded by NIH, versus people who work
at companies, so that's true. And NIH investigators, more and
more, are being asked to put information in the public domain.
So, in--as a generalization, that is true.
Senator Isakson. Dr. Daley, not--I appreciate your comments
on the recent articles on ``amniotonic''--if that's the right--
--
Dr. Daley. Amniotic.
Senator Isakson [continuing]. Pronunciation. This question
does not relate to that. But on deriving embryonic stem cells
for research purposes, which is something everybody, I think,
is for, there are--the differences come down on the
destruction-of-embryos question that Senator Harkin, Senator
Kennedy, and Senator Enzi have all made very quality
statements, on both sides of that particular issue.
At the University of Georgia, three lines, which do receive
NIH funding, were developed--or embryonic stem cell lines done
specifically in diabetes research with eminent scholars--were
derived from the extraction of embryonic stem cells from level-
three gardener-principle grading in the in vitro fertilization
process. Do you have--that's one known alternative that does
not involve the destruction of an embryo that can be implanted
or frozen. Do you know of others?
Dr. Daley. Yeah. I mean, I know of Dr. Stice's work, in
Georgia. In our own lab, we have actually derived five new
lines from embryos that were considered such poor quality that
they would even be discarded before freezing, they're just not
even part of the IVF process. We have derived lines.
There are a number of issues. The efficiency with which you
can derive those lines is significantly lower than using the
embryos that are frozen, the embryos that have been judged to
be of sufficient quality for clinical use, but which would
otherwise be discarded. I think our preference would be to take
advantage of the hundreds of thousands of embryos that are
destined for medical waste. We can use those and make good
lines.
We need new lines. I just had our--our lab had a meeting
yesterday, where we talked about the crazy H9 cells. My lab now
has been growing this one NIH line, H9, for 6 years. It's now
so distorted that we call it ``crazy H9.'' I mean, we really--
we really--you know, we're handcuffed if we can't continue to
innovate in the area of stem cells. There are many, many new
lines--and the lines that model genetic disease, as Dr. Landis
spoke of, these are enormously valuable, and, Why can't we use
our Federal dollars to study them?
The Chairman. Could I ask--if the Senator would yield--
could you expand? You said that the efficiency is not as good.
As I got the thrust of the question, does not destroy the
embryo, but that was the--as I understood what--the Senator has
spoken to me about this. I'm interested in your responses. I
wrote down ``the efficiency is not as good, and we ought to''--
--
Dr. Daley. Yeah.
The Chairman [continuing]. ``Be able to deal with the
others.'' Can you still do it?
Dr. Daley. Well, they----
The Chairman. I mean, is it a way of proceeding
[inaudible]?
Dr. Daley. So, one----
The Chairman. And what would be the disadvantage?
Dr. Daley. Right. One----
The Chairman. Excuse me.
Dr. Daley [continuing]. Strategy that's been put forth as
a--and considered as possibly ethically more acceptable than
using viable embryos is to use the embryos that are deemed of
poor clinical quality. So, at day three in an in vitro
fertilization lab, the embryologists will look at the embryos
and they'll judge whether the cells are intact or whether
they're fragmented or not. And if they're given a choice,
they'll pick ones that look viable, and the ones that have
fragmented will be discarded. We get those embryos, and we use
them.
Now, we believe that they will allow us to make normal stem
cell lines, but I'm not necessarily certain that there aren't
hidden genetic defects in those cells. For some reason, those
embryos didn't form.
The Chairman. Yeah.
Dr. Daley. And so, not only is it much less efficient--it's
about 1 percent of those poor-quality embryos that we can make
yes-cells from. I'm not only concerned about the efficiency,
I'm really concerned about the integrity of those lines.
The Chairman. Senator Lautenberg.
Senator Lautenberg. Thanks, Mr. Chairman.
I listened with interest to the testimony of each one of
you, and I congratulate you for doing it.
But, in particular, Lauren, your story will be listened to
by lots of people. They'll hear your voice, and we're very
proud of you. And I reach out to you, because I'm a grandfather
of 10 grandchildren, and I realize how lucky we are that
they're without any difficulty like the one you have.
And, to Mr. and Mrs. Stanford, I want you to know this.
We've heard the discussion about money, about resources, and
how, ``We just don't have the money.'' What we're saying to
you, in body, is that your priority for Lauren doesn't compare
to the priority of making a war that over two-thirds of the
American people reject. That would represent 200 million people
in our society who don't want us to carry on the war as it is.
But we can't afford to spend more than $130 million on
embryonic stem cell research? I find it difficult to
understand, and I find it shocking. And I defy any member of
the U.S. Senate to tell you that that priority, with that
beautiful young woman, that intelligent young woman, who can
make such a contribution to our society, doesn't rank with a
war that's really distasteful to most of the people in the
country.
Mr. Daley, the lack of the proper investment in stem cell
research has slowed progress. Is there any judgment, any guess,
about how much we've lost by not paying attention to this, by
not making the proper investments to find out what's there?
Dr. Daley. It's always difficult to answer a question about
what might have been, what could have been, if we had had more
resources. I can speak very personally, that this has led to
countless hours of delay working through various institutional
review boards to get approval to do nonpresidential--what we
call nonpresidential work. Raising private money takes
enormous, enormous amounts of time.
We have to set aside, in our laboratory, behind a black
curtain, a room exclusively for privately funded embryonic stem
cell research, where every single pipette, every single bottle,
every single piece of equipment is labeled with a big sign that
says, ``NP,'' which classifies as the nonpresidential
resources. It's an enormous obstruction to progress in this
very vital area of research.
Senator Lautenberg. Mr. Chairman, as we sit here, we hear
about the possibilities that might be there, about relieving
young people, like Lauren, from having to stick their fingers
and so forth. We also know, or we believe, that we're going to
be facing a request for $100 billion for a supplemental for the
war in Iraq, primarily. Yet still, out of $3 billion invested
in stem cell research, only 4 percent was allowed to be
invested in embryonic stem cell research. Thank you.
And thank you, Mr. Chairman, for holding this hearing.
The Chairman. Thank you. Thank you very much, Frank. Thank
you.
Senator Coburn.
Senator Coburn. Thank you.
First of all, let me say how much I appreciate each of you,
in terms of your dedication to what you're doing. The area of
expertise that you're in today is going to be critical for our
future.
And, Lauren, I want to tell you, I've delivered 4,000
babies--I diagnosed a 6-month-old with type-1 diabetes before,
and cared for her until she graduated from college. You have a
great future in front of you, and you can have all the children
you want, with today's management techniques. So, don't worry
about that. And I'd love to see you up there, instead of
Senator Kennedy, I promise you.
[Laughter.]
Besides being a lot better to look at--
[Laughter.]
A couple of points I want to make, and then I want to ask a
couple of questions.
First of all, let's make sure we understand the dividing
line on this debate. Some of us very earnestly believe life
begins at conception. At the moment that sperm and egg divide--
combine, we believe there's life there. And so, that's where
the ethical problem is. And we want to work as hard as we can
to get around that and not rationalize away the fact that we
believe that's life. And that has to be respected. That
position is not taken lightly. Everything about our life
revolves around some of those critically held beliefs. And so,
I won't demean anybody who disagrees with that, but you--we
can't be demeaned because we believe that. And I hope we'll
respect that opinion. That says nothing about us not wanting to
get everywhere you all want to get, in terms of cures.
I'm a two-time cancer survivor. I may be a two-time cancer
survivor, we don't know yet. But the point is--and I have
family--sister-in-law and sister with breast cancer--I mean,
you know, I don't have a very good set of genes, quite frankly.
But the point is, we have hope, too, even those that oppose
this on this very ideal and heartfelt thinking of the value of
the initiation of life.
And I think Senator Isakson is really on to something. And
I think we have a way that we can move a President to sign
money for research, even though it might be harder, but the
idea of nonviable, nonlife-giving embryos to be used to develop
stem lines. And, as you said, Dr. Daley, you don't know yet
whether or not they're a compromised cell line. Well, let's
find out.
I can tell you that there's--you're going to get a veto.
That's No. 1. So, let's send him something that he won't veto
that helps move us down the track. What I would hope is that
you all would agree to work with us to try to come to that
point. Senator Isakson and Senator Coleman have worked hard on
what looks like a great compromise, which we'll be discussing
with people. I can certainly live with it, given my beliefs,
and I'd hope you all would.
The other thing that I want to talk about, and I guess I'd
better ask my question--let me ask my question, and then, if I
get a chance to talk about it again, I will.
Autologous transfer. Dr. Wagner's talked about rejection
with what they've seen so far. But there is no question, there
is more rejection, within the body, of foreign protein than
there is autologous protein. Is that not true?
Dr. Wagner. That's generally correct. However, it may be
different for stem cells.
Senator Coburn. Right. But the fact is, everything we know
about immunology today is, if you put foreign protein into the
body, you're going to have a greater reaction than if you put
your own protein into your body. And so, we have to believe,
until your research proves otherwise, that there's less
likelihood to be a rejection if you were using autologous
cells, if, in fact, we can use autologous cells. And I mean
cells that come from your own body.
And the reason I'm a big believer in the research that's
going--I don't discount, for a minute, the great work that's
going to come from biochemical studies, drug studies, disease-
treatment studies, and disease treatment from embryonic stem
cell research. And I wouldn't discount that for a minute. But
the real cures, in my belief, based on rejection and the
potential for rejection being less with autologous cells, I
believe, is going to come from some type of nonembryonic stem
cells, but maybe more potent or pluripotent, not totipotent
cells.
And I'd just like your comments on what you know in the
literature, in terms of rejection, in terms of mitochondrial
DNA that's going to be a factor in anything that we do, in
terms of embryonic stem cells, in terms of transplantation. And
just a comment on that, for a minute, if you would.
Dr. Wagner. To whom?
Senator Coburn. Either one.
Dr. Wagner. Well, can I start first?
Well, first off, you know, although I didn't get into the
details, the one thing that we also know, based on our work, is
that, because stem cells lack class-one antigens--and I know
that's--doesn't really matter to the majority of you----
[Laughter.]
However, it will be eradicated by natural killer cells. So,
even if it's autologous, it will have an immune reaction.
The second thing is, it's a misconception that if you
believe that--the future is going to be, you know, individual
autologous products, we--it's too expensive and too difficult
to do for each individual patient. Yes, proof of principles can
be established using that, but, in the great future, we're
going to have to do an off-the-shelf product that will not be
completely matched, even with autologous stem cells.
Dr. Daley. Yeah, I would just second that. I would agree
with that.
Senator Coburn. Thank you.
The Chairman. Senator Sanders.
Senator Coburn. Senator Kennedy, I would also like to
submit for the record the RAND study on the availability of
embryos----
The Chairman. Be so included.
Senator Coburn [continuing]. That are out there.
The Chairman. Be so included.
[The information previously referred to follows:]
Senator Sanders. Thank you, Mr. Chairman, for holding this
important hearing. Let me concur with colleagues in
congratulating this extraordinarily wonderful panel for your
testimony.
The House of Representatives recently voted, 253 to 174, to
lift the current limits on Federal funding for embryonic stem
cell research. And I have every reason to believe that the U.S.
Senate is also going to vote in that direction. I certainly
will vote for that.
Unfortunately, we have a situation--and Senator Coburn just
told you what I suspect is the truth--that we have a President
of the United States who will likely veto this legislation. I
think that that is a tragedy, but that is the apparent reality.
The President regards this issue as murder. I, myself, have
a little bit of difficulty understanding that. And the question
that I wanted to ask Dr. Daley is, Isn't it simply true that
embryonic stem cells which are not implanted are simply
discarded and thrown into the trash? Is that the case, or is
that not the case?
Dr. Daley. Well, I mean, there--one has to figure out what
to do with the many, many tens of thousands--some would say
hundreds of thousands--of embryos that are frozen. They're--a
very, very tiny percentage would be adopted by others, a small
number will be used by the couples themselves in future
pregnancies, but the vast majority will be essentially destined
for medical waste, discarded.
Senator Sanders. And these are cells which you are telling
us, today, could possibly lead to huge breakthroughs in a whole
host of diseases which plague millions of Americans and people
throughout the world, is that the case?
Dr. Daley. Well, I mean, I think the extension is that
there are enormous opportunities for using those embryos in
medical research, whether it's for deriving stem cells, which
is only one aspect of embryo research, these are enormously
valuable tools and objects for study.
Senator Sanders. So, on one hand, we are looking at these
cells being discarded, destroyed; on the other hand, we are
looking at these cells being used for research which can make
major breakthroughs in some of the most terrible diseases
facing humanity. Is that really the equation that we're looking
at?
Dr. Daley. I believe that is the direct----
Senator Sanders. Well, you know----
Dr. Daley [continuing]. Equation.
Senator Sanders [continuing]. On many issues, the United
States is being seen in a lower and lower light all over the
world. And I have to say that when people around the world--
when serious people are trying to deal with some of the worst
illnesses and diseases facing humanity, they are wondering what
is going on in our great Nation. And I would hope very much
that all over our country people begin to stand up and express
the long-held faith that we, as Americans, have had in basic
science; that we try to continue the traditions that we have
had as being a nation leading the world in breakthrough
scientific research; and that we give the President of the
United States all of the reasons in the world, scientific and
political, that he should not veto this legislation.
Thank you very much, Mr. Chairman
The Chairman. Thank you very much.
Senator Hatch.
Senator Hatch. Well, thank you, Mr. Chairman.
A lot of my questions have been asked, but I'd like to just
take this time to make some points.
I want to thank all of our distinguished scientists for
taking the time to join us. And I especially want to thank you,
Lauren, for being here--your testimony is very important to me,
and, I think, to all of us here--for gracing us with your
presence.
Mr. Chairman, this hearing is important, because opponents
of embryonic stem cell research point to the fact that there
are no treatments with embryonic stem cells--they say that it's
a failed science. I say it's a handcuff science. And I've
brought----
[Laughter.]
These handcuffs, from one of my Secret Service buddies, to
make that point.
[Laughter.]
Now, think of these handcuffs while you listen to the
expert scientists assembled here. They will tell us that they
and their colleagues are holding the line against spinal cord
injuries, Parkinson's disease, diabetes, and other illnesses.
They are exploring the potential of stem cells from umbilical-
cord blood, of stem cells from amniotic fluid, and, of course,
of stem cells taken from adults, all of which we think is
crucial and important, but they are not advancing as rapidly
against these afflictions as they could by ethically using
frozen cells from--stem cells from frozen and unused embryos,
because their hands are bound.
While all forms of stem cell research should be
aggressively pursued, scientists see great potential in the use
of embryonic stem cells because they have the unique ability to
become any kind of cell in the body, yet we are placing
unnecessary and potentially disastrous obstacles in the way of
scientists who wish to pursue this research to develop
breakthrough treatments.
Let me give you just a few examples.
Dr. Marie Csete is an anesthesiologist and cell biologist
from Emory University who works with embryonic stem cells. She
tells us that the restrictions that current Federal policy
places upon her and her colleagues are, in her words, ``so
odious that many scientists just do not try.'' I'll bet you
agree with that.
Dr. Daley. Yeah.
Senator Hatch. OK. We are wasting researchers' time, we are
wasting their resources, and, in the final analysis, we are
wasting the lives of many people who could be saved.
Now, I commend President Bush for authorizing Federal funds
to study approved human embryonic stem cell lines isolated
before August 2001. He's the only President who has allowed
this. But this was hardly the key to unlock the treatments of
the future. In 2001, there were 71 approved stem cell lines,
that has since dwindled to 21 usable lines. And an NIH-funded
stem cell researcher at the University of Texas, Dr. Ping Wu,
told me that, in reality, there are only 12 usable lines, the
others will not grow. Dr. Wu says the few usable cell lines are
not enough to represent the general population in any way.
Furthermore, these lines are contaminated with animal cells,
mouse feeder cells, if you will, and, therefore, can never be
placed in humans.
Dr. Linda Kelley, who happens to be here today, is an
associate professor of medicine at the University of Utah,
somebody I greatly admire. She told me that the approved cell
lines are so unstable that--I know I'm taking a little more
time. Is that all right, Mr. Chairman?
The Chairman. That's--you're always----
[Laughter.]
You always have something useful to say.
[Laughter.]
And so, we're glad to----
Senator Hatch. He doesn't dare prohibit me, I'll tell you.
I know how to get to him.
The Chairman. Yeah.
[Laughter.]
Senator Hatch. But Dr. Kelley is an associate professor of
medicine at the University of Utah. She told me that the
approved cell lines are so unstable that, in her words, ``You
are lucky if you can recover 10 percent of the cells they send
to you.'' Now, she said the cells have been reused for so long
that they have degraded and no longer represent the human
population at all. And I'll bet you agree with that.
Another unintended consequence of the President's policy is
the creation of monopolies. Many owners of these few approved
stem cell lines have used their monopoly to make the cells very
expensive and difficult to obtain.
Dr. Rick Wetsel, at the University of Texas Health Center,
told me about paying $5,000 for one approved cell line, only to
find that the cells were worthless, forcing him to pay another
$5,000 and wait 6 months for a new batch. Another scientist,
Dr. Csete, who I mentioned before, was charged $20,000 for what
should have been a $500 cell line. The cells they've purchased
have been reproduced so many times that they do not live very
long and cannot be used with normal laboratory techniques. So,
they are spending more money for less valuable material.
These restrictions also waste time and effort. NIH funds
are the bedrock of every university's research program. Hardly
a piece of equipment or a technician in a medical school, is
not in some way, supported by NIH. You agree with that, don't
you? You bet your life.
Ms. Landis. Yes.
[Laughter.]
Senator Hatch. Medical school deans and scientists are
afraid of violating Federal law by allowing equipment and
personnel funded by the NIH to touch a nonapproved cell line.
You all agree with that.
Dr. Wetsel, in Houston, spent several years obtaining
enough funds from a private donor to work with a fresh cell
line derived from a discarded frozen embryo. He was forced to
use most of the precious funds to buy duplicate equipment and
then place it in a small laboratory that was isolated from the
rest of his NIH-funded facility.
Dr. Csete told me that she is unable to send her doctors-
in-training to study stem cell techniques in expert
laboratories that work with nonapproved lines, because their
salaries were funded by NIH.
Scientists in the United States are either walking away
from embryonic stem cell research or they're walking away from
the United States.
Now, Mr. Chairman, let me just cite one more proof of how
our current policy is handcuffing this promising research.
In the first 6 years after human embryonic stem cells were
discovered, at the University of Wisconsin in 1998, half of the
20 most quoted publications on this research came from the
United States. But a closer look at these publications is
troubling. Seven of those ten U.S. publications came from the
University of Wisconsin and Geron Corporation, both heavily
endowed with private funding. Only 3 of the 125 U.S. academic
medical centers contributed a top human embryonic stem cell
publication in the 6 years after their discovery. If the United
States is to remain among the world's leaders in this research,
that simply must change. We must give scientists who want to
work with embryonic stem cells a chance, just like we do for
stem cells from cord blood, amniotic fluid, and from adults,
all of which I support strongly.
As Professor Kelley told me, ``There is so much to be
learned, and it is terribly frustrating.'' It shouldn't be that
way. It doesn't have to be that way. And I think we've got to
unlock these handcuffs and let our scientists find these
treatments and cures that'll help Lauren and others similarly
situated. And that's all you want, is a chance to really make
these things go.
And last, but not least, I said, after we had won this
debate on the floor of the Senate--in the press conference
afterwards, I said, ``Look, there are at least 300 embryonic
stem cell lines that are fertile and working in our society
today. Why can't we, since the Government had not participated
in the destruction of the embryo, allow NIH to partner with
those 300--with those companies and those 300 lines that would
partner with them''--and I think they all would--``so that we
can push this research forward?'' That's what was the theory
behind the original 71 stem cell lines that the President said
we could have. Why not do that? And I don't think it's a good
answer to say, ``Well, that would encourage them to continue to
destroy embryos.''
I just want to tell you how much your testimonies, all of
you, have meant. And the leadership of these fellows sitting up
in front here--and we're happy to have Bernie Sanders with us.
I've got to admit, I was worried about that, but I----
[Laughter.]
I appreciated his comments this morning.
But I want to thank each of you. I think you've made
excellent statements. They're straightforward, they're honest,
and, frankly, accurate and true.
Sorry, Mr. Chairman, I took too long, I know that.
The Chairman. Well, thank you. We'll forgive that extra
time, as long as you get the SCHIP out of the Finance Committee
to look at our health insurance for the----
[Laughter.]
Senator Hatch. Well, we got it out before.
The Chairman. That's right.
Senator Allard, thank you for your patience and for joining
our committee. I look forward to hearing from you.
Senator Allard. Well, thank you, Mr. Chairman. And I
appreciate the fact that you're holding this hearing. It's the
first opportunity I've had to listen to testimony from the NIH.
And I'm going to, kind of, steer away from the political
arguments and focus a little bit on the science and kind of
look at it from a practical aspect.
It's obvious that we've got a problem with the number of
dollars that you can use for research; you have to set
priorities. The other challenge that I see are that we have an
ethical concern raised by some members of this committee. I
know, in the scientific community, we also have those ethical
concerns.
So, the question that I see before us is, How do we take a
patient like Lauren--by the way, I'm a veterinarian, so I've
had some medical training--but how do you take a patient like
Lauren, and how do you most quickly get a remedy for her
juvenile diabetes?
And I'd also bring out another axiom, in veterinary
medicine, when we use a more specific treatment, the fewer side
effects we're going to deal with. That's true in immunology,
too. We're developing vaccines whose antigens are more
specific, so you have fewer reactions to it.
As I picked up from your testimony, we have a huge
immunolog-
ical problem here. It seems to me that we would do best to
focus on stem cells for islet cells than we would to focus our
efforts on a pluripotent type of cell, that, in the long run,
the chances of coming up with a treatment that would have fewer
immunological problems would be to take a specific approach
like that.
My question to both of the physicians that are here is, In
your research, in trying to set priorities, have you thought
about taking this type of approach, as opposed to an omnipotent
approach and if you have, how far along are you in this? I
mean, have we identified--the questions have come up--have we
identified stem cells for islet cells, or have we identified
stem cells for pancreatic cells, in general? Just how far along
are we in that? And I think that would help us in our debate.
Dr. Daley. Yeah. So, if we speak about type-1 diabetes,
which is the loss of insulin-producing beta cells, and the best
hope for cure for Lauren is to replace those beta cells. It is
currently highly controversial as to whether or not her body,
or any of our bodies, actually possess stem cells that
regenerate insulin-producing beta cells. Highly controversial.
It is, however----
Senator Allard. So, some are saying that they believe there
is that----
Dr. Daley. Some are saying it's----
Senator Allard [continuing]. Possibility, some say that
it----
Dr. Daley. And it's----
Senator Allard [continuing]. Doesn't.
Dr. Daley. And so----
Senator Allard. Yeah.
Mr. Daley [continuing]. The way to balance the priorities
of research are to let expert scientists make those decisions.
I don't think those priorities are well decided here in the
Halls of Congress. And that's done through a very extensive and
rigorous peer-review system that the NIH has pioneered. I think
that's where the decisions should be made.
Dr. Wagner. But just to further that, when stuff--
basically, you know, all those avenues are being pursued,
perhaps at one institution, or many institutions. But I can
tell you, even at our own institution, we're exploring not only
islets, as a form of therapy gotten from the patient--him or
herself--we're also exploring the use of sibling donors, also
exploring unrelated donors for islets, as well as porcine
donors, the pig donors, for islets, as a strategy for treating
human patients with diabetes, in addition to multipotent adult
stem cells, in addition to embryonic stem cells. But going back
to the analogy that Mr. Harkin had, you know, stated years ago,
Why would we ever want to close any of those doors, when we
don't know which one will be the true therapy that will have
the most benefit for the patients with diabetes? We don't want
to close any door. And that's what the scientists are asking
for, that ability.
Senator Allard. Well, the problem I have with that is you
know, maybe not close the door, but what you need to do is, you
need to look at where you're going to most likely get the best
results from the taxpayer dollars that you're spending. I mean,
that's----
Dr. Wagner. But we don't----
Senator Allard [continuing]. That's the challenge we have.
And I think it's----
Dr. Daley. Right.
Senator Allard [continuing]. Your challenge, as
researchers----
Dr. Daley. And that's the challenge----
Senator Allard [continuing]. To convince us----
Mr. Daley [continuing]. Of the peer-review process----
Senator Allard. Yeah--is to convince us----
Mr. Daley [continuing]. To determine the right----
Senator Allard [continuing]. As scientists----
Dr. Daley [continuing]. Priority.
Senator Allard [continuing]. That you have that plan and
you've given that some thought. And that's the reason I bring
up the arguments in the way I did, because the challenge I
think you have, as scientists, to present to us, as
policymakers, Where you are going to get the best results
that'll get the quickest cure for Lauren while realizing we
have a limited resource in taxpayer dollars. We just can't--we
can't open every door----
Dr. Wagner. Sure.
Senator Allard [continuing]. So we have to take a look at
those doors that most likely will open up to a quicker
solution.
Dr. Wagner. Well, in response to that, I think that, you
know, we're already doing it. All the doors are open. It's just
some of the doors are being markedly slowed down.
But the fact is, is that you're asking for the answer
before the researchers know what the answer is. We don't know
what the best therapy will be. Of course, in the meantime, we
explore what we can do, and that is, we can look at islets as a
form of cellular therapy. But I would believe, based on the
results that we have so far, that islet transplants themselves
are a short-term fix, they don't reproduce themselves for the
life of the patient. Maybe we'll figure out a way of doing that
in the future, but right now we don't know. And how can I
speculate what I don't know? So, we have to explore all the
options. And I think that we're doing that.
Ms. Landis. So, if I could just add, for nervous-system
diseases, the evidence is pretty clear that adult stem cells,
and even, most recently, the amniotic-fluid-derived stem cells,
really aren't going to provide us with the tools that we need.
We now have recipes to create dopamine neurons for Parkinson's,
motor neurons for spinal cord injury, oligodendrocytes, or
ensheathing cells, for spinal cord injury, retinal progenitor
cells. And that's been done within the 5 years since the
President's policy was put----
Senator Allard. Yeah.
Ms. Landis [continuing]. In place.
Senator Allard. Yeah.
Ms. Landis. And if, with Senator Hatch's handcuffs, we've
been able to do that, imagine what the opportunities are
without the handcuffs.
Senator Allard. Thank you.
The Chairman. Thank you.
Senator Hatch.
Senator Hatch. Mr. Chairman, could I just ask the whole
panel--the three doctors one question?
The Chairman. Certainly.
Senator Hatch. Sorry to go out of turn, but----
Dr. Landis, we'll start with you. In your opinion--and I
think this is an important question--if NIH funds were made
available for research, you know, on all ethically obtained
embryos from in vitro fertilization, would the probability of
finding treatments and/or cures, we'll put it that way--for
human diseases, increase or decrease?
Ms. Landis. Absolutely it would increase. There's no
question about that.
Senator Hatch. Just barely, or would you have a real
opportunity to----
Ms. Landis. We would have a real opportunity. I can give
you one specific example. Huntington's disease is an inherited
disease, triplet repeat disease, causes a particular kind of
death of neuron in the brain. We have no good animal models. We
don't know why those cells die. We don't know how to stop that
process. If we had embryonic stem cells derived from discarded
embryos that were not implanted, we would be able to make
extraordinary inroads into therapeutics for that disease.
Senator Hatch. Dr. Daley.
Dr. Daley. I would say, in general, any investment in basic
biomedical research is an incredibly important investment for
this country. It pays off handsomely, in terms of human health.
It's now an issue of national security, given the issues around
bioterrorism. And we, in general, will derive enormous economic
benefit, long-term economic benefit, from raising the overall
NIH budget, not just stem cells.
Senator Hatch. For embryonic stem cells.
Mr. Wagner.
Dr. Wagner. The first thing that I'd do, like Dr. Kelley,
would be to actually derive cell lines that would be perfect
for use in clinical settings and for patients, which--none of
them currently exist today. Second thing I'd do is, I would
actually then make you also think about that this is more than
just a cell therapy. As Dr. Daley previously mentioned, these
cells also give us an unprecedented ability to look at new
drugs. We can look at molecular events and better understand
why diseases occur. So, it's much more than just a cell
therapy.
So, it would have a profound effect. But, also, from a
practical point of view, right now the restrictions that we
have are, as you've heard, just getting the ability to be able
to take the cell that's newly derived and be able to give it to
our neighbor in Iowa or to be able to then give it to the lab
next door, outside the confounds of what the Government will
allow us, because these are NIH-funded labs, would make it just
extraordinarily easy for us to make advances rapidly.
Senator Hatch. Lauren, we want to help all people like you.
And these great scientists can do it, if their hands are not
handcuffed. And we've just got to make sure they're not
handcuffed. We're going to win on this, but it's a shame that
it's been 3, 4 years since we really started putting a drive on
it. And, for the life of me, I can't understand how some of my
friends believe that discarding, as hospital waste, 7,000 to
20,000 embryos a year is the right thing to do. We ought to be
utilizing them for Lauren and people who similarly suffer.
We've just got to wake up on this; untie your hands and allow
you to really do the research that has to be done.
This group--many in this hearing today are really dedicated
to trying to do that. And others are very sincerely on the
other side, but it's just a matter of time. We've just got to
move this forward.
And I particularly appreciated your testimony in front of
NIH today. I know it took a lot of courage for you to do that.
The Chairman. Thank you.
Senator Hatch. Thank you.
The Chairman. Senator Hatch, like our colleagues Senators
Harkin, Specter, and others, has been a real leader in this
whole----
Senator Hatch. Thanks.
The Chairman [continuing]. And I want to pay tribute to his
leadership. It's been very, very important.
And I had just one final question, if I could. All of you
have been extremely patient. And that is, Dr. Landis, could we
talk about those ethical restrictions that we have in the
research now that guide Federal research, not necessarily
applicable to other research? One of the powerful arguments
that can be made is, with the Federal research, on that, there
are going to be the appropriate kind of ethical guidelines
which are so----
Ms. Landis. Right.
The Chairman [continuing]. Important, in a major----
Ms. Landis. Right.
The Chairman [continuing]. New area----
Ms. Landis. Right.
The Chairman [continuing]. Of research.
Ms. Landis. So, I----
The Chairman. Just----
Ms. Landis [continuing]. I think it's very----
The Chairman [continuing]. Just briefly----
Ms. Landis [continuing]. Clear that federally funded
research has monitoring, oversight, and transparency that
privately funded research will not necessarily have, and that,
to the extent that embryonic stem cell research is funded by
Federal dollars, then that research will benefit from those
oversight procedures.
The Chairman. I think it's very important that it's been
included in the legislation from the beginning.
Tom.
Senator Harkin. Mr. Chairman, again, I want to thank
everyone for being here and for hanging in there on this and
continuing to inform us and enlighten us on the various aspects
of all the different forms of stem cell research. And I just
want to make it clear for the record, from my standpoint, this
Senator's standpoint, I'm a strong supporter of all stem cell
research. I made that clear from the very beginning, whether
it's adult stem cell, amniotic, cord blood--I think these are
all worthy of the most profound research that we can do in our
society. And they can all lead to different things. Some may be
good here. You used the analogy of the seeds. Some may be good
here, Dr. Wagner, for what you're doing out there; some may be
good some other place.
But I think what Senator Hatch said was really very
important and we've got to keep it in mind. I had asked Dr.
Daley this question before, about why don't we just leave it to
the States and private entities? Senator Hatch, I think you've
really hit upon a key part of that, and that is--and I've heard
this from scientists around the country that, because NIH
funding is so pervasive through universities and academic
research centers and everything else, that if they want to do
this kind of research, the hoops they've got to go through. If
California moves ahead on what they're doing, they will be
building separate buildings, separate research centers just to
do this. What a waste of money and resources. Scientists right
now have to set up different rooms and different labs, and they
can't use their computers at night, because those computers are
used also for NIH-funded research, so they can't get online and
do that.
Last, one of the analogies I would make on why this is so
important for Federal research, is that this committee funded
the first money into the human genome research in 1989. Dr.
Watson came to see us. We started putting money in it. And out
of that came the human genome center at NIH and the mapping and
sequencing of the human gene. What's so wonderful about that is
not only the knowledge that we've gained from that, but the
fact that it's free for everybody. It's out there. Anyone,
anywhere in the world, can go in there and find all that
information. Now, if we had left that just to the private
sector--and, believe me, I love Craig Venter, he's been a
friend of mine, he's done great research, but the fact is that
we would have had snippets, perhaps, of different parts of the
genome that would have been available, at a great, high price
that Senator Hatch was talking about, and others, but we might
not have had the whole genome mapped and sequenced. But the
fact is, you can go online right now, and you can find any one
of those 3 billion pairs anywhere, and it's available for
research. It seems to me, stem cell research lends itself to
this kind of thing. And I don't mean just embryonic stem cells,
I mean all stem cell research, that if it's done by NIH, and
funded by NIH, you get it done ethically, you have monitoring,
you don't have duplication, it's much more efficient and
effective, you have scientists talking to one another in free
form, and all the results of that information is available to
the public. It's available to anyone.
And, who knows, there might be a young Lauren someplace
who's just a budding young scientist, not bound by old concepts
and old ways of doing things, that sees some research being
done there and say, ``I think I can do something different with
that.'' It's one of those young scientists that's going to find
how to take some of these cells and move them in different
directions. That, to me, is the promise of all this.
I love the handcuffs. I mean, I think that was really
illustrative of what we're talking about here, Senator Hatch,
and getting the handcuffs off of the Federal Reserve.
Dr. Daley. Senator Harkin.
Senator Harkin. Who said something?
Dr. Daley. I'm sorry, if I could just return to your issue
of the ethical oversight of stem cell research, I want to make
the point that scientists are very motivated to do the research
in a climate of rigorous and ethical oversight, and the
International Society for Stem Cell Research is about to
announce a set of guidelines to govern the conduct, to
establish rules of play for scientists. These are guidelines
that have been vetted through an international committee. And
what we're hoping is that scientists all over the world, well
beyond the reach of U.S. oversight, will agree to the same
common set of ethical principles so that the public, worldwide,
can really embrace this science.
Senator Harkin. Well, I pointed out before that the bill
that we're talking about here, that we passed last year, the
same one we're talking about now, has stronger ethical
guidelines and strictures on it than what's in existing law
right now. Very strong ethical guidelines. As you know, the
research can only be done on those embryos left over in in
vitro fertilization clinics and has to have the fully informed
written consent of the donors. No money can change hands, so
there can't be any farming and that kind of stuff; it has to be
done voluntarily with fully informed written consent and only
with those embryos that would be discarded anyway. And last,
they can only be used for stem cell research--can't be used for
implantation and other things, only be used for stem cell
research. To me, these are pretty tough ethical guidelines,
right there. Tougher than what we have in existing law right
now. I always say to my friends that if they want more ethical
standards, well, we have them in our bill, and they're there.
Well, Mr. Chairman, again, thank you very much for this
joint hearing. We will continue to pursue this on both levels,
on yours and on the Appropriations Committee. And, of course,
we are hoping, Dr. Landis, with your great leadership, and the
whole NIH, that we can have a better budget for NIH, this next
year. It's unconscionable to me, and I know it is to my good
friend Arlen Specter, that we are fighting, right now, just to
get funding for NIH at the 2005 level. It's not that we're
asking for a big increase, we're just trying to get back to the
2005 level in the budget. Hopefully this year we can move it
ahead, and more aggressively. And again, if we do that and open
up these doors, perhaps we can make some really, really
significant progress so that Lauren can become that Senator in
Massachusetts.
[Laughter.]
The Chairman. That's good.
Senator Harkin. So, thank you very much.
The Chairman. Tom, thanks so much. You can feel Senator
Harkin's passion about this issue, and can see why he's such a
leader in this undertaking.
Senator Hatch just has a final few questions and--like to
address the panel.
Senator Hatch. I'm sorry to keep you a little bit longer,
but this is an important question. We'll start with you, Dr.
Wagner, and then have the three doctors give a crack at this.
I don't know if you're all aware of it, but the Web site
for the organization called Do No Harm lists 71 diseases that
are treatable by adult stem cells. Among the diseases listed
spinal cord injury, stroke, and Parkinson's disease. Now, three
clinical scientists from three separate academic medical
centers reviewed this Web site and concluded that adult stem
cells were clinically proven, and FDA approved to treat only 9
diseases, not 71.
So, my question on that is this. Which is the correct
number? How many diseases are you aware of that are treatable
by adult stem cells currently? I'm for pushing adult stem cell
research as fast as we can, as far as we can, but I don't want
to have misrepresentations if these doctors are right, that
there are only 9 diseases and not 71.
Dr. Wagner. Well, I think that within the context, as I
presented, the context of using adult stem cells, the only
proven use of adult stem cells is in the setting of bone marrow
transplant to treat leukemia----
Senator Hatch. Right.
Dr. Wagner [continuing]. Bone-marrow failure. As far as I
know, there is no proven use of adult stem cells. However, are
there FDA-sponsored or, you know, monitored trials that are
ongoing to ask the question, you know, Would this be useful
therapy? Yes, there's quite a few different therapies currently
being explored, but are not yet definitive.
Senator Hatch. But to say that there are 71 currently in
use would not be a good representation by a scientist.
Dr. Wagner. No, it's misleading. Seventy-one may be under
study, but certainly have not been proven.
Senator Hatch. Dr. Daley.
Dr. Daley. Yeah, I mean, with all due respect to Dr.
Wagner's fabulous contributions to bone marrow transplantation,
this is not a panacea, this is a heroic, highly toxic form of
therapy which is really used in an attempt to save people with
fatal diseases. To say that we don't need embryonic stem cells,
because look at all this success with adult stem cells, is
really to deny the fact that the current therapies are
inadequate. They are just grossly inadequate. The future is in
pushing research so that we can truly have curative therapies
for those 71 diseases.
Senator Hatch. Do you agree with that?
Ms. Landis. So, I actually have the letter to Science--it
was in the July 13 issue--in front of me, from Smith, Neaves,
and Teitelbaum, which lists the evidence indicated that there
are 9 and not 71, and you might want to have it introduced into
the record.
Senator Hatch. I'll ask the Chairman to introduce it in the
record.
[Editor's Note: The information previously referred to can be found
at www.sciencemag.org.]
[Response by Prentice and Tarne to the above letter can be found in
Additional Material.]
Ms. Landis. And it's very clear that there are nine
approved--FDA-approved, clinically tested treatments, but that
is all that presently exist. NIH believes it's critical to
continue to fund all kinds of stem cell research so that,
again, we can move that 9 closer to the 71.
Senator Hatch. Dr. Landis, are you aware of any young
scientists who have redirected their research interest because
of the lack of Federal funding for embryonic stem cell
research?
Ms. Landis. I know of many young scientists who are
finishing their training who are very reluctant to move into,
or retain activities in, human embryonic stem cell research,
because of all of the complexities that you've heard to date.
Senator Hatch. Well, now, Dr. Daley, let me just finish
with these questions. Really, this panel has been one of the
best panels I've ever heard on healthcare. And I've heard a lot
of them over the last 30 years with my friends on my left here.
And we've sat through a lot of hearings, and this has been a
great panel. But, Dr. Daley, opponents of embryonic stem cell
research have made much of the fact that these cells are
reported to produce tumors in experimental animals. What are
scientists' views on this problem? And how do you think the
potential for amniotic stem cells may prove to stack up against
embryonic stem cells as potential therapies, or is it too early
to tell?
Dr. Daley. We know about this issue, that embryonic stem
cells form a type of benign encapsulated mass, which is called
a tumor. We have strategies for dealing with that. No one is
thinking about any kind of cell therapy that would involve
transplanting the undifferentiated stem cells. You
predifferentiate, you make the tissue of interest, the highly
specialized insulin-producing cell or blood cell--those are not
tumorigenic cells. It's an issue of safety, it's an issue of
clinical testing. We're at the earliest stages, we know about
it, and we're going to anticipate it, and we're going to look
very, very hard for ways to get around it.
Senator Hatch. Then you believe you can solve that problem.
Dr. Daley. We do believe we can solve that problem, yes.
Senator Hatch. OK. Now, what about the potential for
amniotic stem cells that--how may they prove to stack up
against embryonic stem cells as potential therapies or--again,
is it too----
Dr. Daley. Yeah.
Senator Hatch [continuing]. Early to tell?
Dr. Daley. Well, amniotic stem cells are fascinating. They
are not embryonic stem cells. They will not do everything that
embryonic stem cells do. But we have work, at the Children's
Hospital, with kids who are diagnosed with diaphragmatic
hernias, in ultrasound, in utero. You can take the amniotic
cells, you can grow a patch to be used in that child. This is a
very exciting application of this work. In no way should one
choose embryonic over amniotic. They both need to be studied,
and we need more funding to do it.
Senator Hatch. So, they're complementary.
Dr. Daley. They're complementary, not competitive.
Senator Hatch. Do either of the other two doctors care to
comment about that?
Dr. Wagner?
Ms. Landis. So, if I could just say, there's a paper
recently that's received a lot of attention. Cells
differentiated into dopamine neurons transplanted in human
embryonic stem cells, differentiated into dopamine neurons
transplanted into a rat model of Parkinson's, and they did, in
fact, see tumors. I would say that this is one of a number of
studies, and, in the other studies, there was no evidence of a
teratoma or a tumor. And the point that Dr. Daley has made is
that almost certainly undifferentiated cells were transplanted,
and, by selecting the differentiated from the undifferentiated,
you can prevent tumor formation. So, this is----
Senator Hatch. OK.
Ms. Landis [continuing]. An unusual----
Senator Hatch. But you can use embryonic stem cells to
reach the differentiated status, is----
Ms. Landis. Right.
Senator Hatch [continuing]. What I----
Ms. Landis. Right.
Senator Hatch [continuing]. Understand----
Ms. Landis. Right. Right.
Senator Hatch [continuing]. Dr. Daley said.
Dr. Wagner, we'll finish with you.
Dr. Wagner. My only comment was really to emphasize that,
you know, all the data suggests, exactly as Dr. Daley had
indicated, that there are strategies that we can employ to
overcome this issue of teratomas from the embryonic stem cells.
Furthermore, you know, the idea of using amniotic stem cells as
a future therapy currently is--certainly needs to be explored,
but it's currently all speculative, at this point, where it
will go. Again, we need to explore all the options.
Senator Hatch. But without exploring it, we will never----
Dr. Wagner. We'll never know.
Senator Hatch [continuing]. Be able to know whether we can
arrive at these treatments or cures that could save us
trillions of dollars in healthcare costs and maybe make a lot
of the current surgical procedures and other procedures not
necessary. I see this as the only way we're going to stop our
healthcare budget from just consuming the whole Federal budget.
But it's going to take years. That's what science is all about.
It's not something you snap your fingers about, it's something
that takes years and years, by brilliant people, who basically
never give up, and who can get around these so-called
``problems'' by continued research.
And I just want to compliment all of you here today. And,
Lauren, thank you for taking time to be here. You're the most
sophisticated--and you're in ninth grade, you say?
Ms. Stanford. Uh-huh.
Senator Hatch. You're the most sophisticated ninth grader
I've ever met in the Senate, so I just want you to know that.
[Laughter.]
The Chairman. So, thank you.
Just concluding, I'm a great believer that we are in the
life-science century, and we have--the opportunities for
breakthroughs are unlimited, and the impact that it can have on
the quality of life in our families and for our country, and,
as was pointed out, for our economy, in--an innovative new
economy with all the implications that that has in--for people
that are working in this and for leading the world, and
demonstrate our interest in helping to solve the human
condition in other parts of the world. We have--all of this is
a breathtaking possibility. And this is an aspect of it, in
terms of the stem cell research that is just an indispensable
aspect of it. So, we are very strong supporters.
What I want to just say is, we have every intention, for
those that are here today, of having this on the Senate floor.
This is a--priorities in the House, and we have talked to the
leadership, our Democratic leader, hopefully with our
Republican leader, as--that I mentioned, Senator Hatch has been
a strong leader on this issue. We've had a very strong
bipartisan commitment. But this is going to be on the--this is
a high priority, and we expect this to be considered--the
earlier the better, but certainly in February. And so, this is
moving ahead, and this hearing will be really instrumental.
And we want to just conclude by congratulating Lauren's
parents, too, for doing a great job.
The committee stands in recess.
[Additional material follows:]
ADDITIONAL MATERIAL
Supporting Material for Treating Diseases with Adult Stem Cells
david a. prentice and gene tarne
TABLE S1. DISEASE AND CONDITION CHART
List of conditions in which adult stem cell use produced therapeutic
benefit for human patients (1)
------------------------------------------------------------------------
Quotes from Smith,
Neaves, Teitelbaum Additional
Disease or Condition (emphasis added) Comments
(2)
------------------------------------------------------------------------
Brain Tumors.................... Two clinical Clinical
(Medulloblastoma and Glioma) (3- studies and one improvement shown
5). literature review by peer-reviewed
indicated that reference.
some patients who
have their brain
cancers treated
with high-dose
chemotherapy show
improved long-
term survival
rates when
transplants of
adult stem cells
from bone marrow
or blood are used
to alleviate side
effects of the
chemotherapy.
Retinoblastoma (6-7)............ Two clinical Clinical
reports indicated improvement shown
that a small by peer-reviewed
group of patients reference.
with malignant
retinoblastoma
show improved
survival rates
when transplants
of adult stem
cells from bone
marrow or blood
are used to
alleviate side
effects of
chemotherapy.
Ovarian Cancer (8-9)............ One clinical study Clinical
and one improvement shown
literature review by peer-reviewed
indicated that a reference.
subset of ovarian
cancer patients
responds better
to high-dose
chemotherapy when
treatment is
followed by adult
stem cell
transplants.
Merkel Cell Carcinoma (10)...... A case study Clinical
reporting that a improvement shown
single Merkel by peer-reviewed
cell carcinoma reference.
patient showed a
longer-than
expected survival
time when given
an adult stem
cell transplant
after
chemotherapy.
Testicular Cancer (11).......... Bhatia et al. One technical
described a reference
clinical removed.
evaluation Remaining
showing improved reference not
long-term mentioned by
survival of Smith et al. in
relapsed letter.
testicular cancer Clinical
patients improvement shown
following a by peer-reviewed
radical therapy reference.
that included a
transplant of
adult stem cells
from bone marrow
or blood.
Lymphoma (12-14)................ Three clinical Clinical
reports of improvement shown
various lymphoma by peer-reviewed
types and patient reference.
numbers indicated
that some
patients show
improved long-
term survival
when adult stem
cell transplants
follow high-dose
chemotherapy.
Non-Hodgkin's Lymphoma (15-18).. Three clinical One technical
studies reported reference
that some non- removed.
Hodgkin's Three references
lymphoma patients not mentioned by
show improved Smith et al. in
long-term letter.
survival when Clinical
adult stem cell improvement shown
transplants by peer-reviewed
follow high-dose reference.
chemotherapy.
Hodgkin's Lymphoma (19-20)...... Two clinical Clinical
studies indicated improvement shown
that some by peer-reviewed
patients with reference.
Hodgkin's
lymphoma show
overall improved
survival rates
when transplanted
with adult stem
cells from blood.
Acute Lymphoblastic Leukemia (21- Two clinical Clinical
23). studies, each improvement shown
incorporating by peer-reviewed
multiple leukemia reference.
types, indicated FDA-approved
that adult stem through phase IV
cell transplants clinical trials
from bone marrow according to
or umbilical cord Smith et al.
blood improve the
survival of
children with
leukemia when the
transplants are
performed during
the early phase
of disease.
Adult stem cell
transplants from
bone marrow or
blood can induce
lasting remission
when leukemias
are diagnosed
early.
Acute Myelogenous Leukemia (24- Three clinical Clinical
27). studies indicated improvement shown
that AML patients by peer-reviewed
who receive adult reference.
stem cell FDA-approved
transplants after through phase IV
initial disease clinical trials
remission according to
demonstrate Smith et al.
improved overall
survival.
Adult stem cell
transplants from
bone marrow or
blood can
accomplish
significant
improvements in
the survival of
early-stage AML.
Chronic Myelogenous Leukemia (28- Two clinical Clinical
29). studies, each improvement shown
incorporating by peer-reviewed
multiple leukemia reference.
types, indicated FDA-approved
that adult stem through phase IV
cell transplants clinical trials
from bone marrow according to
or umbilical cord Smith et al.
blood improve the
survival of
children with
leukemia when the
transplants are
performed during
the early phase
of disease.
Adult stem cell
transplants from
bone marrow or
blood can induce
lasting remission
when leukemias
are diagnosed
early.
Juvenile Myelomonocytic Leukemia Two clinical Clinical
(30). studies, each improvement shown
incorporating by peer-reviewed
multiple leukemia reference.
types, indicated FDA-approved
that adult stem through phase IV
cell transplants clinical trials
from bone marrow according to
or umbilical cord Smith et al.
blood improve the
survival of
children with
leukemia when the
transplants are
performed during
the early phase
of disease.
Adult stem cell
transplants from
bone marrow or
blood can induce
lasting remission
when leukemias
are diagnosed
early.
------------------------------------------------------------------------
Angioimmunoblastic A case study Clinical
Lymphadenopathy (31). reported that a improvement shown
single AILD by peer-reviewed
patient reference.
experienced an
extended disease-
free period after
receiving high-
dose chemotherapy
and a transplant
of stem cells
derived from
blood.
Multiple Myeloma (32-33)........ Vesole et al. Clinical
showed that a improvement shown
high-dose by peer-reviewed
chemotherapy reference;
regimen followed updated.
by transplanting FDA-approved
adult stem cells through phase IV
from blood clinical trials
resulted in according to
modest survival Smith et al.
improvements in
half of study
participants.
Myelodysplasia (34-35).......... Two clinical Clinical
studies, each improvement shown
incorporating a by peer-reviewed
small number of reference.
patients with FDA-approved
myelodysplasia, through phase IV
suggested that clinical trials
high-dose according to
chemotherapy in Smith et al.
combination with
adult stem cell
transplants from
bone marrow or
umbilical cord
blood improve the
survival of
myelodysplasia
patients,
particularly when
this treatment is
performed during
the early phase
of disease.
Adult stem cell
transplants from
bone marrow or
blood enable
myelodysplasia
patients to
withstand a
higher dose of
chemotherapy,
thereby
increasing the
chances of the
treatment
inducing lasting
remission.
Breast Cancer (36-39)........... Four clinical Clinical
studies reported improvement shown
that patients by peer-reviewed
with high-risk or reference.
advanced breast
cancer had
improved survival
rates when
intensive
radiation and/or
chemotherapy was
followed by a
transplant of
adult stem cells
derived from bone
marrow or blood.
Neuroblastoma (40).............. A clinical study Clinical
indicated that improvement shown
transplantation by peer-reviewed
of adult stem reference.
cells derived
from blood is
associated with
improved survival
rates for a
specific kind of
high-risk
neuroblastoma.
Renal Cell Carcinoma (41-44).... One clinical study Clinical
and one case improvement shown
report indicated by peer-reviewed
that, in patients reference;
with metastatic updated.
renal cell
carcinoma,
transplants of
donated adult
stem cells from
blood delayed
cancer spread and
resulted in
overall increase
in long-term
survival of some
patients.
Soft Tissue Sarcoma (45)........ One clinical study Clinical
indicated that improvement shown
some STC patients by peer-reviewed
exhibited higher reference.
survival rates
when treated with
adult stem cells
from blood after
high-dose
chemotherapy.
------------------------------------------------------------------------
Various Solid Tumors (46-50).... Four clinical Clinical
studies improvement shown
evaluating the by peer-reviewed
safety and/or reference.
efficacy of adult
stem cell
transplants as a
treatment for
various solid
tumors (inc.
breast, ovarian,
pediatric brain
cancers) showed
that adult stem
cell transplants
may reduce
chemotherapy-
related side
effects for some
cancer patients.
Waldenstrom's Macroglobulinemia One clinical study Clinical
(51). indicated that improvement shown
some WM patients by peer-reviewed
receiving both reference.
high-dose
chemotherapy and
a transplant of
bloodforming stem
cells showed
improved survival
rates.
Hemophagocytic A case study Clinical
Lymphohistiocytosis (52). reported that a improvement shown
child with HLH by peer-reviewed
received a reference.
transplant of
stem cells
donated by the
patient's mother
2 months after a
transplant of
liver tissue from
the same parent.
The patient was
disease-free for
4 months post-
stem cell
transplant.
POEMS Syndrome (Osteosclerotic An initial Clinical
Myeloma) (53). clinical study improvement shown
indicated that by peer-reviewed
transplants of reference.
adult stem cells
from blood
alleviated some
of the symptoms
of POEMS.
------------------------------------------------------------------------
Systemic Lupus (54-62).......... Early reports Clinical
suggest that improvement shown
immune by peer-reviewed
reconstitution by reference.
adult stem cell
transplants may
induce an
extended disease-
free period in
some lupus
patients who have
failed
conventional
therapies.
Sjogren's Syndrome (63)......... ``Resetting'' the Clinical
immune system improvement shown
with chemotherapy by peer-reviewed
and an adult stem reference.
cell transplant
may induce an
extended disease-
free state in
some patients
with Sjorgen's
syndrome.
Myasthenia (64)................. .................. Clinical
improvement shown
by peer-reviewed
reference.
Autoimmune Cytopenia (65-66).... ``Resetting'' the One technical
immune system reference
with chemotherapy removed.
and an adult stem Clinical
cell transplant improvement shown
may induce an by peer-reviewed
extended disease- reference;
free state in updated.
some patients
with this
disease, and a
more recent
clinical study
suggests that
such treatment
can confer
benefit to some
patients in spite
of a risk of
severe side
effects.
Scleromyxedema (67)............. More recent Clinical
evidence improvement shown
indicates that by peer-reviewed
high-dose reference.
chemotherapy
followed by
transplants of
blood-forming
stem cells
reverse many
disease symptoms
for an extended
period, but this
treatment is not
curative.
Scleroderma (68-69)............. Two literature Clinical
reviews written improvement shown
by the same first by peer-reviewed
author described reference.
early clinical
studies of adult
stem cell
transplants as a
treatment for
various
autoimmune
diseases. The
authors propose
that these
transplants can
cause disease
remission in some
patients.
Crohn's Disease (70-73)......... Initial, small- Clinical
scale clinical improvement shown
evaluations by peer-reviewed
suggest that this reference.
combination
approach can
suppress disease
in some patients
who fail standard
treatments, but
the adult stem
cell transplants
are intended to
help patients
survive the
immune
suppressive
regimen, not
directly treat
the disease.
Behcet's Disease (74)........... ``Resetting'' the Clinical
immune system improvement shown
with chemotherapy by peer-reviewed
and an adult stem reference.
cell transplant
has been observed
to induce an
extended disease-
free state in
some patients
with Behcet's
disease.
Rheumatoid Arthritis (75-81).... Five early Clinical
clinical studies improvement shown
and two by peer-reviewed
literature reference.
reviews indicated
that transplants
of adult stem
cells, either
donated or from
the patient him/
herself, in
combination with
radical use of
conventional
therapies (e.g.,
immune
suppression,
chemotherapy and/
or radiation)
delay the course
of rheumatoid
arthritis in some
patients with
advanced disease.
More recent
evidence suggests
that some
patients with
severe rheumatoid
arthritis who
have failed
conventional
therapies can
experience an
extended disease-
free period when
adult stem cell
transplants are
used as part of a
radical treatment
protocol.
Juvenile Arthritis (82-84)...... More recently, Clinical
adult stem cell improvement shown
transplants have by peer-reviewed
been used in reference;
combination with updated.
immune
suppression or
radiation
treatment.
Results indicate
that about half
the patients show
disease remission
following this
treatment.
Multiple Sclerosis (85-90)...... The combination of Clinical
adult stem cell improvement shown
transplantation by peer-reviewed
and radical reference.
therapy decreased
the number of
observable MS
lesions, but
following the
extent of disease-
free remission
would have
required further
study. More
recent research
indicates that
radical
treatments that
include adult
stem cell
transplants can
improve the
overall quality
of life of
patients with
severe multiple
sclerosis (for
whom there are no
effective
alternative
treatments).
However, the
transplant's
ability to
reverse the onset
of MS remains
unproven, and in
most cases the
transplant is
intended to help
alleviate the
side effects of
harsh
chemotherapy and/
or immune
suppression.
Polychondritis (91)............. The single patient Clinical
included in the improvement shown
cited study was by peer-reviewed
reported to have reference.
achieved an
extended disease-
free period.
Systemic Vasculitis (92)........ ``Resetting'' the Clinical
immune system improvement shown
with chemotherapy by peer-reviewed
and an adult stem reference.
cell transplant
has been observed
to induce an
extended disease-
free state in
some patients
with systemic
vasculitis.
Alopecia Universalis (93)....... This reference was Clinical
a case study improvement shown
reporting that a by peer-reviewed
lymphoma patient reference.
who received a
bone marrow
transplant also
experienced hair
regrowth.
------------------------------------------------------------------------
Severe Combined Immunodeficiency In some patients, Clinical
Syndrome-X1 (94-95). this therapy is improvement shown
curative, though by peer-reviewed
immune rejection reference.
concerns persist FDA-approved
throughout the through phase IV
life of the clinical trials
patient. according to
Smith et al.
X-Linked Lymphoproliferative In some patients, Clinical
Syndrome And X-Linked this therapy is improvement shown
Hyperimmunoglobulin M Syndrome curative, though by peer-reviewed
(96-97). it remains reference.
experimental.
Immune rejection
concerns persist
throughout the
life of the
patient, and it
is not a suitable
treatment option
for all patients.
Sickle Cell Anemia (98-103)..... One case report Clinical
and one improvement shown
observational by peer-reviewed
clinical study reference;
(totaling updated.
experience with 5
patients)
indicated that
adult stem cell
transplants from
bone marrow or
umbilical cord
blood can provide
some benefit to
sickle cell
patients. A third
literature review
proposed that
adult stem cell
transplants hold
the potential to
treat sickle cell
anemia because
sickle cell
results from a
defect in blood-
forming stem
cells in bone
marrow, restoring
healthy stem
cells to a
patient's bone
marrow can
reverse the
disease.
Sideroblastic Anemia (104-105).. These references Clinical
were two small improvement shown
clinical studies by peer-reviewed
suggesting that reference.
transplants of
adult stem cells
from bone marrow
or blood can
reverse
sideroblastic
anemia for an
extended period.
Aplastic Anemia (106-107)....... Combinations of Clinical
immune improvement shown
suppression and by peer-reviewed
adult stem cell reference
transplantation FDA-approved
can improve the through phase IV
long-term clinical trials
survival of according to
aplastic anemia Smith et al.
patients.
Red Cell Aplasia (108).......... Transplants of Clinical
donated blood- improvement shown
forming stem by peer-reviewed
cells in reference;
combination of updated.
chemotherapy may
improve the long-
term survival of
some patients.
Amegokaryocytic Thrombocytopenia Combinations of Clinical
(109). chemotherapy, improvement shown
immune by peer-reviewed
suppression and reference.
adult stem cell
transplants have
been proposed as
a potentially
curative
treatment.
However, due to
the small number
of patients
affected by this
disease, this
treatment
protocol remains
experimental.
Thalassemia major (110)......... This reference is Clinical
a case report improvement shown
indicating that a by peer-reviewed
transplant of reference. FDA-
donated blood- approved through
forming stem phase IV clinical
cells suppressed trials according
disease in two to Smith et al.
thalassemia
patients. Severe
thalassemia is
often treated by
bone marrow
transplantation,
although this
procedure carries
considerable risk
and is not
suitable for all
patients.
Primary Amyloidosis (111)....... This reference is Clinical
a literature improvement shown
review proposing by peer-reviewed
that transplants reference.
of adult stem
cells from blood
and high-dose
chemotherapy
provide an
improved
treatment for
primary
amyloidosis. On a
small scale,
adult stem cell
transplants have
been shown to
benefit patients
with advanced
disease, though
significant
treatment-related
side effects were
reported.
Diamond Blackfan Anemia (112)... Adult stem cell Clinical
transplants can improvement shown
reverse bone by peer-reviewed
marrow failure in reference.
some patients,
but they do not
alter the genetic
defect underlying
the disease and
so are not
curative.
Fanconi's Anemia (113-115)...... Adult stem cell Clinical
transplants can improvement shown
reverse bone by peer-reviewed
marrow failure in reference;
some patients, updated.
but they do not
alter the genetic
defect underlying
the disease and
so are not
curative.
Chronic Epstein-Barr Infection High-dose Clinical
(116-117). chemotherapy and improvement shown
bone marrow by peer-reviewed
replenishment has reference.
been reported to
reduce the amount
of active virus
in the body and
can improve
survival of some
patients.
Hurler's Syndrome (118-120)..... One retrospective Clinical
analysis and one improvement shown
small clinical by peer-reviewed
study indicated reference;
that adult stem updated.
cell transplants
protected some of
the tissues
attacked by
Hurler's syndrome
but provided
little relief to
other tissues.
Long-term
survival was
improved, with
the greatest
benefit seen in
children
transplanted
early in life.
Osteogenesis Imperfecta (121- Three clinical Clinical
123). studies, all from improvement shown
the same first by peer-reviewed
author, suggested reference.
that transplants
of bone-forming
stem cells from
bone marrow are
feasible and can
improve the bone
growth of
children
suffering from
osteogenesis
imperfecta.
Krabbe Leukodystrophy (124-125). Two early clinical Clinical
studies reported improvement shown
that cognitive by peer-reviewed
impairments from reference.
Krabbe's disease
are reduced when
children are
treated with
transplants of
donated umbilical
cord blood stem
cells.
Osteopetrosis (126-128)......... These references Clinical
were one improvement shown
retrospective by peer-reviewed
analysis and one reference;
small clinical updated.
study indicating
that transplants
of adult stem
cells from bone
marrow (either
donated or from
the patient him/
herself) improve
the long-term
survival of some
children with a
certain kind of
osteopetrosis.
Cerebral X-Linked This reference was Clinical
Adrenoleukodystrophy (129). one retrospective improvement shown
analysis by peer-reviewed
indicating that reference.
transplants of
adult stem cells
from blood
improve the long-
term survival of
some patients
with early-stage
cerebral Xlinked
adrenoleukodystro
phy. Roughly half
of study subjects
ultimately
succumbed to the
disease, and the
transplant
therapy was shown
to be
significantly
less effective
for children with
advanced disease.
Sandhoff Disease................ .................. Removed from list
awaiting peer-
reviewed report.
Corneal Regeneration (130-138).. All papers Clinical
reported improvement shown
regeneration of by peer-reviewed
the cornea and reference.
improved vision Smith et al.
in a subset of misstate
patients. repetition of
reports.
Limb Gangrene (139)............. One pilot study Clinical
reported that improvement shown
implantation of by peer-reviewed
bone marrow stem reference.
cells into non-
healing skin
ulcers restored
some blood flow
to the affected
area and
accomplished
moderate repair.
Surface Wound Healing (140)..... .................. Switched animal &
clinical paper.
Clinical
improvement shown
by peer-reviewed
reference;
updated.
Jaw Bone Replacement (141)...... A case report Clinical
detailed a tissue improvement shown
engineering by peer-reviewed
approach to reference.
making a new jaw
for a patient who
had lost his to
cancer. By this
technique, a jaw-
shaped metal
frame is seeded
with bone marrow
stem cells and
growth-promoting
drugs before
implantation in
the patient's
shoulder. After 7
weeks bone grew
over the frame
and was then
removed from the
shoulder and
installed as the
patient's new jaw.
Skull Bone Repair (142)......... A case report Clinical
described a improvement shown
tissue by peer-reviewed
engineering reference.
approach to
closing a large
skull fracture.
The open portion
of the patient's
skull was covered
with a protein-
based glue that
had fat stem
cells seeded
within it. New
bone growth was
observed 3 months
after this
procedure.
Acute Heart Damage (143-159).... Seven experimental Clinical
or early phase improvement shown
clinical studies, by peer-reviewed
including one reference.
placebo-
controlled
clinical trial,
indicated that
transfusion of a
patient's own
bone marrow-
derived stem
cells into the
heart shortly
after heart
attack is
relatively safe
and is associated
with regeneration
of heart tissue
and improved
heart function.
The cited studies
suggest that
transplantation
of adult stem
cells from bone
marrow is
associated with
improved recovery
after heart
attack.
------------------------------------------------------------------------
Stroke (160-163)................ Three experimental Clinical
studies reported improvement shown
that implantation by peer-reviewed
of brain stem reference;
cells into the updated.
brains of long-
term stroke
patients was
feasible and
relatively safe.
Parkinson's Disease (164-166)... .................. Removed abstract &
2 Congressional
testimonies.
Valid stimulation
of endogenous
stem cells not
mentioned by
letter authors.
Clinical
improvement shown
by peer-reviewed
reference;
updated.
Spinal Cord Injury (167)........ .................. Removed 3
Congressional
testimonies.
Clinical
improvement shown
by peer-reviewed
reference.
------------------------------------------------------------------------
NOTES: Column 1 shows the disease or condition listed as treated, with
peer-reviewed sample references. Column 2 lists comments validating
patient improvement from the supplement of Smith, Neaves and
Teitelbaum. Column 3 provides additional information regarding listed
references.
REFERENCES
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16 July 2006).
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supplementary data at Science Online at www.sciencemag.org/cgi/
content/full/1129987/DC1.
3. Dunkel, IJ; ``High-dose chemotherapy with autologous stem cell
rescue for malignant brain tumors''; Cancer Invest. 18, 492-493;
2000.
4. Abrey, LE et al.; ``High dose chemotherapy with autologous stem cell
rescue in adults with malignant primary brain tumors''; J.
Neurooncol. 44, 147-153; Sept., 1999.
5. Finlay, JL; ``The role of high-dose chemotherapy and stem cell
rescue in the treatment of malignant brain tumors: a reappraisal'';
Pediatr.Transplant 3 Suppl. 1, 87-95; 1999.
6. Hertzberg H et al.; ``Recurrent disseminated retinoblastoma in a 7-
year-old girl treated successfully by high-dose chemotherapy and
CD34-selected autologous peripheral blood stem cell
transplantation''; Bone Marrow Transplant 27(6), 653-655; March
2001.
7. Dunkel IJ et al.; ``Successful treatment of metastatic
retinoblastoma''; Cancer 89, 2117-2121; Nov 15 2000.
8. Stiff PJ et al.; ``High-dose chemotherapy and autologous stem-cell
transplantation for ovarian cancer: An autologous blood and marrow
transplant registry report''; Ann. Intern. Med. 133, 504-515; Oct.
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160. Shyu W-C et al., Granulocyte colony-stimulating factor for acute
ischemic stroke: a randomized controlled trial, Canadian Medical
Association Journal 174, 927-933, 28 March 2006.
161. Stilley CS et al., Changes in cognitive function after neuronal
cell transplantation for basal ganglia stroke, Neurology 63, 1320-
1322, October 2004.
162. Meltzer CC et al.; ``Serial [18F]Fluorodeoxyglucose Positron
Emission Tomography after Human Neuronal Implantation for Stroke'';
Neurosurgery 49, 586-592; 2001.
163. Kondziolka D et al.; ``Transplantation of cultured human neuronal
cells for patients with stroke''; Neurology 55, 565-569; August
2000.
164. Love S et al., Glial cell line-derived neurotrophic factor induces
neuronal sprouting in human brain, Nature Medicine 11, 703-704,
July 2005.
165. Slevin JT et al., Improvement of bilateral motor functions in
patients with Parkinson disease through the unilateral
intraputaminal infusion of glial cell line-derived neurotrophic
factor, Journal of Neurosurgery 102, 216-222, February 2005.
166. Gill SS et al.; ``Direct brain infusion of glial cell line-derived
neurotrophic factor in Parkinson disease''; Nature Medicine 9, 589-
595; May 2003 (published online 31 March 2003).
167. Lima C et al., Olfactory mucosa autografts in human spinal cord
injury: A pilot clinical study, Journal of Spinal Cord Medicine 29,
191-203, July 2006.
Peer-Reviewed References Showing Applications of Adult Stem Cells That
Produce Therapeutic Benefit for Human Patients
(not a complete listing, sample references)
adult stem cells--hematopoietic replacement
cancers
BRAIN TUMORS--medulloblastoma and glioma
Dunkel, IJ; ``High-dose chemotherapy with autologous stem cell rescue
for malignant brain tumors''; Cancer Invest. 18, 492-493; 2000.
Abrey, LE et al.; ``High dose chemotherapy with autologous stem cell
rescue in adults with malignant primary brain tumors''; J.
Neurooncol. 44, 14: -153; Sept., 1999.
Finlay, JL; ``The role of high-dose chemotherapy and stem cell rescue
in the treatment of malignant brain tumors: a reappraisal'';
Pediatr. Transplant 3 Suppl. 1, 8: -95; 1999.
RETINOBLASTOMA
Hertzberg H et al.; ``Recurrent disseminated retinoblastoma in a : -
year-old girl treated successfully by high-dose chemotherapy and
CD34-selected autologous peripheral blood stem cell
transplantation''; Bone Marrow Transplant 2: (6), 653-655; March
2001.
Dunkel IJ et al.; ``Successful treatment of metastatic
retinoblastoma''; Cancer 89, 211: -2121; Nov 15 2000.
OVARIAN CANCER
Stiff PJ et al.; ``High-dose chemotherapy and autologous stem-cell
transplantation for ovarian cancer: An autologous blood and marrow
transplant registry report''; Ann. Intern. Med. 133, 504-515; Oct.
3, 2000.
Schilder, RJ and Shea, TC; ``Multiple cycles of high-dose chemotherapy
for ovarian cancer''; Semin. Oncol. 25, 349-355; June 1998.
MERKEL CELL CARCINOMA
Waldmann V et al.; ``Transient complete remission of metastasized
merkel cell carcinoma by high-dose polychemotherapy and autologous
peripheral blood stem cell transplantation''; Br. J. Dermatol. 143,
83: -839; Oct 2000.
TESTICULAR CANCER
Bhatia S et al.; ``High-dose chemotherapy as initial salvage
chemotherapy in patients with relapsed testicular cancer''; J.
Clin. Oncol. 18, 3346-3351; Oct. 19, 2000.
LYMPHOMA
Tabata M et al.; ``Peripheral blood stem cell transplantation in
patients over 65 years old with malignant lymphoma--possibility of
early completion of chemotherapy and improvement of performance
status''; Intern Med 40, 4: 1-4: 4; June 2001.
Josting, A; ``Treatment of Primary Progressive Hodgkin's and Aggressive
Non-Hodgkin's Lymphoma: Is There a Chance for Cure?''; J Clin Oncol
18, 332-339; 2000.
Koizumi M et al.; ``Successful treatment of intravascular malignant
lymphomatosis with high-dose chemotherapy and autologous peripheral
blood stem cell transplantation''; Bone Marrow Transplant 2: 1101-
1103; May 2001.
NON-HODGKIN'S LYMPHOMA
Buadi FK et al., Autologous hematopoietic stem cell transplantation for
older patients with relapsed non-Hodgkin's lymphoma, Bone Marrow
Transplant 3: , 101: -1022, June 2006.
Tabata M et al.; ``Peripheral blood stem cell transplantation in
patients over 65 years old with malignant lymphoma--possibility of
early completion of chemotherapy and improvement of performance
status''; Intern Med 40, 4: 1-4: 4; June 2001.
Josting, A; ``Treatment of Primary Progressive Hodgkin's and Aggressive
Non-Hodgkin's Lymphoma: Is There a Chance for Cure?''; J Clin Oncol
18, 332-339; 2000.
Kirita T et al.; ``Primary non-Hodgkin's lymphoma of the mandible
treated with radiotherapy, chemotherapy, and autologous peripheral
blood stem cell transplantation''; Oral Surg Oral Med Oral Pathol
Oral Radiol Endod. 90, 450-455; Oct. 2000.
HODGKIN'S LYMPHOMA
Peggs KS et al., ``Clinical evidence of a graft-versus-Hodgkin's-
lymphoma effect after reduced-intensity allogeneic transplantion,''
Lancet 365, 1934-1941, 4 June 2005.
Josting, A; ``Treatment of Primary Progressive Hodgkin's and Aggressive
Non-Hodgkin's Lymphoma: Is There a Chance for Cure?''; J Clin Oncol
18, 332-339; 2000.
ACUTE LYMPHOBLASTIC LEUKEMIA
Laughlin MJ et al.; ``Hematopoietic engraftment and survival in adult
recipients of umbilical-cord blood from unrelated donors,'' New
England Journal of Medicine 344, 1815-1822; June 14, 2001.
Ohnuma K et al.; ``Cord blood transplantation from HLA-mismatched
unrelated donors as a treatment for children with haematological
malignancies''; Br J Haematol 112(4), 981-98: ; March 2001.
Marco F et al.; ``High Survival Rate in Infant Acute Leukemia Treated
With Early High-Dose Chemotherapy and Stem-Cell Support''; J Clin
Oncol 18, 3256-3261; Sept. 15 2000.
ACUTE MYELOGENOUS LEUKEMIA
Laughlin MJ et al.; ``Hematopoietic engraftment and survival in adult
recipients of umbilical-cord blood from unrelated donors,'' New
England Journal of Medicine 344, 1815-1822; June 14, 2001.
Ohnuma K et al.; ``Cord blood transplantation from HLA-mismatched
unrelated donors as a treatment for children with haematological
malignancies''; Br J Haematol 112(4), 981-98: ; March 2001.
Gorin NC et al.; ``Feasibility and recent improvement of autologous
stem cell transplantation for acute myelocytic leukaemia in
patients over 60 years of age: importance of the source of stem
cells''; Br. J. Haematol. 110, 88: -893; Sept 2000.
Bruserud 0 et al.; ``New strategies in the treatment of acute
myelogenous leukemia: mobilization and transplantation of
autologous peripheral blood stem cells in adult patients''; Stem
Cells 18, 343-351; 2000.
CHRONIC MYELOGENOUS LEUKEMIA
Laughlin MJ et al.; ``Hematopoietic engraftment and survival in adult
recipients of umbilical-cord blood from unrelated donors,'' New
England Journal of Medicine 344, 1815-1822; June 14, 2001.
Ohnuma K et al.; ``Cord blood transplantation from HLA-mismatched
unrelated donors as a treatment for children with haematological
malignancies''; Br J Haematol 112(4), 981-98: ; March 2001.
JUVENILE MYELOMONOCYTIC LEUKEMIA
Ohnuma K et al.; ``Cord blood transplantation from HLA-mismatched
unrelated donors as a treatment for children with haematological
malignancies''; Br J Haematol 112(4), 981-98: ; March 2001.
CHRONIC MYELOMONOCYTIC LEUKEMIA
Elliott MA et al., Allogeneic stem cell transplantation and donor
lymphocyte infusions for chronic myelomonocytic leukemia, Bone
Marrow Transplantation 3: , 1003-1008, 2006.
ANGIOIMMUNOBLASTIC LYMPHADENOPATHY with DYSPROTEINEMIA
Lindahl J et al.; ``High-dose chemotherapy and APSCT as a potential
cure for relapsing hemolysing AILD''; Leuk Res 25(3), 26: -2: 0;
March 2001.
MULTIPLE MYELOMA
Aviles A et al., Biological modifiers as cytoreductive therapy before
stem cell transplant in previously untreated patients with multiple
myeloma, Annals of Oncology 16, 219-221, 2005.
Vesole, DH et al.; ``High-Dose Melphalan With Autotransplantation for
Refractory Multiple Myeloma: Results of a Southwest Oncology Group
Phase II Trial''; J Clin Oncol 1: , 21: 3-21: 9; July 1999.
MYELODYSPLASIA
Ohnuma K et al.; ``Cord blood transplantation from HLA-mismatched
unrelated donors as a treatment for children with haematological
malignancies''; Br J Haematol 112(4), 981-98: ; March 2001.
Bensinger WI et al.; ``Transplantation of bone marrow as compared with
peripheral-blood cells from HLA-identical relatives in patients
with hematologic cancers''; New England Journal of Medicine 344, 1:
5-181; Jan 18 2001.
BREAST CANCER
Damon LE et al.; ``High-dose chemotherapy and hematopoietic stem cell
rescue for breast cancer: experience in California''; Biol. Blood
Marrow Transplant 6, 496-505; 2000.
Paquette, RL et al., ``Ex vivo expanded unselected peripheral blood:
progenitor cells reduce posttransplantation neutropenia,
thrombocytopenia, and anemia in patients with breast cancer,''
Blood 96, 2385-2390; October, 2000.
Stiff P et al.; ``Autologous transplantation of ex vivo expanded bone
marrow cells grown from small aliquots after high-dose chemotherapy
for breast cancer''; Blood 95, 2169-21: 4; March 15, 2000.
Koc, ON et al.; ``Rapid Hematopoietic Recovery After Coinfusion of
Autologous-Blood Stem Cells and Culture-Expanded Marrow Mesenchymal
Stem Cells in Advanced Breast Cancer Patients Receiving High-Dose
Chemotherapy''; J Clin Oncol 18, 30: -316; January 2000.
NEUROBLASTOMA
Kawa, K et al.; ``Long-Term Survivors of Advanced Neuroblastoma With
MYCN Amplification: A Report of 19 Patients Surviving Disease-Free
for More Than 66 Months''; J Clin Oncol 1: :3216-3220; October
1999.
RENAL CELL CARCINOMA
Barkholt L et al., Allogeneic haematopoietic stem cell transplantation
for metastatic renal carcinoma in Europe, Annals of Oncology
published online 28 April 2006.
Arya M et al., Allogeneic hematopoietic stem-cell transplantation: the
next generation of therapy for metastatic renal cell cancer, Nat
Clin Pract Oncol. 1, 32-38, Nov 2004.
Childs R et al., ``Regression of Metastatic Renal-Cell Carcinoma after
Nonmyeloablative Allogeneic Peripheral-Blood Stem-Cell
Transplantation,'' New England Journal of Medicine 343, : 50-: 58;
Sept. 14, 2000.
Childs, RW; ``Successful Treatment of Metastatic Renal Cell Carcinoma
With a Nonmyeloablative Allogeneic Peripheral-Blood Progenitor-Cell
Transplant: Evidence for a Graft-Versus-Tumor Effect'':; J Clin
Oncol 1: , 2044-2049; July 1999.
SOFT TISSUE SARCOMA
Blay JY et al.; ``High-dose chemotherapy with autologous hematopoietic
stem-cell transplantation for advanced soft tissue sarcoma in
adults''; J. Clin. Oncol. 18, 3643-3650; Nov 1 2000.
EWING'S SARCOMA
Drabko K et al., Megachemotherapy followed by autologous stem cell
transplantation in children with Ewing's sarcoma, Pediatric
Transplantation 9, 618-621, 2005.
VARIOUS SOLID TUMORS
Pedrazolli P et al., High dose chemotherapy with autologous
hematopoietic stem cell support for solid tumors other than breast
cancer in adults, Annals of Oncology published online 1: March
2006.
Nieboer P et al.; ``Long-term haematological recovery following high-
dose chemotherapy with autologous bone marrow transplantation or
peripheral stem cell transplantation in patients with solid
tumours''; Bone Marrow Transplant 2: , 959-966; May 2001.
Lafay-Cousin L et al.; ``High-dose thiotepa and hematopoietic stem cell
transplantation in pediatric malignant mesenchymal tumors: a phase
II study''; Bone Marrow Transplant 26, 62: -632; Sept. 2000.
Michon, J and Schleiermacher, G. ``Autologous haematopoietic stem cell
transplantation for paediatric solid tumors,'' Baillieres Best
Practice Research in Clinical Haematology 12, 24: -259, March-June,
1999.
Schilder, RJ et al.; ``Phase I trial of multiple cycles of high-dose
chemotherapy supported by autologous peripheral-blood stem cells'';
J. Clin. Oncol. 1: , 2198-220: ; July 1999.
WALDENSTROM'S MACROGLOBULINEMIA
Anagnostopoulos A et al.; ``High-dose chemotherapy followed by stem
cell transplantation in patients with resistant Waldenstrom's
macroglobulinemia''; Bone Marrow Transplant 2: , 102: -1029; May
2001.
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
Matthes-Martin S et al.; ``Successful stem cell transplantation
following orthotopic liver transplantation from the same
haploidentical family donor in a girl with hemophagocytic
lymphohistiocytosis''; Blood 96, 399: -3999; Dec 1, 2000.
POEMS SYNDROME (OSTEOSCLEROTIC MYELOMA)
Dispenzieri A et al., Peripheral blood stem cell transplantation in 16
patients with POEMS syndrome, and a review of the literature, Blood
104, 3400-340: , 15 November 2004.
MYELOFIBROSIS
Cornetta K et al., Umbilical cord blood transplantation in adults:
results of the prospective Cord Blood Transplantation (COBLT), Biol
Blood Marrow Transplant 11, 149-160, February 2005.
Cervantes F, Modern management of myelofibrosis, Br J Haematol 128,
583-592, March 2005.
Kroger N et al., Pilot study of reduced-intensity conditioning followed
by allogeneic stem cell transplantation from related and unrelated
donors in patients with myelofibrosis, Br J Haematol 128, 690-69: ,
March 2005.
Thiele J et al., Dynamics of bone marrow changes in patients with
chronic idiopathic myelofibrosis following allogeneic stem cell
transplantation, Histol Histopathol 20, 8: -89, July 2005.
Rondelli D et al., Allogeneic hematopoietic stem-cell transplantation
with reduced-intensity conditioning in intermediate- or high-risk
patients with myelofibrosis with myeloid metaplasia, Blood 105,
4115-4119, 15 May 2005.
Benesova P et al., [Complete regression of bone marrow fibrosis
following allogeneic peripheral blood stem cell transplantation in
a patient with idiopathic myelofibrosis] [Article in Czech], Cesk
Patol 40, 16: -1: 1, October 2004.
ADULT STEM CELLS-IMMUNE SYSTEM REPLACEMENT
autoimmune diseases
SYSTEMIC LUPUS
Burt RK et al., Nonmyeloablative hematopoietic stem cell
transplantation for systemic lupus erythematosus, Journal of the
American Medical Association 295, 52: -535, February 1, 2006.
Burt RK et al., ``Induction of tolerance in autoimmune diseases by
hematopoietic stem cell transplantation: getting closer to a
cure?,'' Blood 99, : 68-: 84, 1 February 2002.
Wulffraat NM et al.; ``Prolonged remission without treatment after
autologous stem cell transplantation for refractory childhood
systemic lupus erythematosus''; Arthritis Rheum 44(3), : 28-: 31;
March 2001.
Rosen O et al.; ``Autologous stem-cell transplantation in refractory
autoimmune diseases after in vivo immunoablation and ex vivo
depletion of mononuclear cells''; Arthritis res. 2, 32: -336; 2000.
Traynor AE et al.; ``Treatment of severe systemic lupus erythematosus
with high-dose chemotherapy and haemopoietic stem-cell
transplantation: a phase I study''; Lancet 356, : 01-: 0: ; August
26, 2000.
Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell Transplantation: A
New Therapy for Autoimmune Disease''; Stem Cells 1: , 366-3: 2;
1999.
Burt RK et al.; ``Hematopoietic stem cell transplantation of multiple
sclerosis, rheumatoid arthritis, and systemic lupus
erythematosus''; Cancer Treat. Res. 101, 15: -184; 1999.
Traynor A and Burt RK; ``Haematopoietic stem cell transplantation for
active systemic lupus erythematosus''; Rheumatology 38, : 6: -: :
2; August 1999.
Martini A et al.; ``Marked and sustained improvement 2 years after
autologous stem cell transplant in a girl with system sclerosis'';
Rheumatology 38, : : 3; August 1999.
SJOGREN' S SYNDROME
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
MYASTHENIA
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
AUTOIMMUNE CYTOPENIA
Passweg, JR et al., Haematopoetic stem cell transplantation for
refractory autoimmune cytopenia, British Journal of Haematology
125, : 49-: 55, June 2004.
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
SCLEROMYXEDEMA
A.M. Feasel et al., ``Complete remission of scleromyxedema following
autologous stem cell transplantation,'' Archives of Dermatology 13:
, 10: 1-10: 2; Aug. 2001.
SCLERODERMA
Burt RK et al., ``Induction of tolerance in autoimmune diseases by
hematopoietic stem cell transplantation: getting closer to a
cure?,'' Blood 99, : 68-: 84, 1 February 2002.
Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell Transplantation: A
New Therapy for Autoimmune Disease''; Stem Cellsl: , 366-3: 2;
1999.
CROHN'S DISEASE
Kreisel W et al., Complete remission of Crohn's disease after high-dose
cyclophosphamide and autologous stem cell transplantation, Bone
Marrow Transplantation 32, 33: -340, 2003.
Burt RK et al., ``High-dose immune suppression and autologous
hematopoietic stem cell transplantation in refractory Crohn
disease,'' Blood 101, 2064-2066, March 2003.
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
Hawkey CJ et al.; ``Stem cell transplantation for inflammatory bowel
disease: practical and ethical issues''; Gut 46, 869-8: 2; June
2000.
BEHCET'S DISEASE
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
RHEUMATOID ARTHRITIS
Burt RK et al., ``Induction of tolerance in autoimmune diseases by
hematopoietic stem cell transplantation: getting closer to a
cure?,'' Blood 99, : 68-: 84, 1 February 2002.
Burt RK et al., ``Induction of remission of severe and refractory
rheumatoid arthritis by allogeneic mixed chimerism,'' Arthritis &
Rheumatism 50, 2466-24: 0, August 2004.
Verburg RJ et al.; ``High-dose chemotherapy and autologous
hematopoietic stem cell transplantation in patients with rheumatoid
arthritis: results of an open study to assess feasibility, safety,
and efficacy''; Arthritis Rheum 44(4), : 54-: 60; April 2001.
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell Transplantation: A
New Therapy for Autoimmune Disease''; Stem Cellsl: , 366-3: 2;
1999.
Burt RK et al.; ``Hematopoietic stem cell transplantation of multiple
sclerosis, rheumatoid arthritis, and systemic lupus
erythematosus''; Cancer Treat. Res. 101, 15: -184; 1999.
Burt, RK et al., ``Autologous hematopoietic stem cell transplantation
in refractory rheumatoid arthritis: sustained response in two of
four patients,'' Arthritis & Rheumatology 42, 2281-2285, November,
1999.
JUVENILE ARTHRITIS
I M de Kleer et al., Autologous stem cell transplantation for
refractory juvenile idiopathic arthritis: analysis of clinical
effects, mortality, and transplant related morbidity, Ann Rheum Dis
63, 1318-1326, 2004.
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell Transplantation: A
New Therapy for Autoimmune Disease''; Stem Cellsl: , 366-3: 2;
1999.
MULTIPLE SCLEROSIS
Saccardi R et al., Autologous HSCT for severe progressive multiple
sclerosis in a multicenter trial: impact on disease activity and
quality of life, Blood 105, 2601-260: , 15 March 2005.
Burt RK et al., ``Induction of tolerance in autoimmune diseases by
hematopoietic stem cell transplantation: getting closer to a
cure?,'' Blood 99, : 68-: 84, 1 February 2002.
Mancardi GL et al.; ``Autologous hematopoietic stem cell
transplantation suppresses Gd-enhanced MRI activity in MS'';
Neurology 5: , 62-68; July 10, 2001.
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
Burt, RK and Traynor, AE; "Hematopoietic Stem Cell Transplantation: A
New Therapy for Autoimmune Disease''; Stem Cellsl: , 366-3: 2;
1999.
Burt RK et al.; ``Hematopoietic stem cell transplantation of multiple
sclerosis, rheumatoid arthritis, and systemic lupus
erythematosus''; Cancer Treat. Res. 101, 15: -184; 1999.
POLYCHONDRITIS
Rosen O et al.; ``Autologous stem-cell transplantation in refractory
autoimmune diseases after in vivo immunoablation and ex vivo
depletion of mononuclear cells''; Arthritis res. 2, 32: -336; 2000.
SYSTEMIC VASCULITIS
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
ALOPECIA UNIVERSAL
Seifert B et al., Complete remission of alopecia universalis after
allogeneic hematopoietic stem cell transplantion, Blood 105, 426-
42: , 1 January 2005.
BUERGER'S DISEASE
Kim D-I et al., Angiogenesis facilitated by autologous whole bone
marrow stem cell transplantation for Buerger's disease, Stem Cells
24, 1194-1200, 2006.
immunodeficiencies
SEVERE COMBINED IMMUNODEFICIENCY SYNDROME
Grunebaum E et al., Bone marrow transplantation for severe combined
immune deficiency, Journal of the American Medical Association 295,
508-518, 1 February 2006.
Cavazzana-Calvo M et al.; ``Gene therapy of human severe combined
immunodeficiency (SCID)-X1 disease''; Science 288, 669-6: 2; April
28, 2000. (NOTE: gene therapy using bone marrow adult stem cells as
gene vehicle)
X-LINKED LYMPHOPROLIFERATIVE SYNDROME and
X-LINKED HYPERIMMUNOGLOBULIN M SYNDROME
Banked unrelated umbilical cord blood was used to reconstitute the
immune system in 2 brothers with X-linked lymphoproliferative
syndrome and 1 boy with X-linked hyperimmunoglobulin-M syndrome.
Two years after transplantation, all 3 patients have normal immune
systems. These reports support the wider use of banked partially
matched cord blood for transplantation in primary
immunodeficiencies.
Reference: Ziegner UH et al.; ``Unrelated umbilical cord stem cell
transplantation for X-linked immunodeficiencies''; J Pediatr
138(4), 5: 0-5: 3; April 2001.
Eight children with severe immunodeficiencies treated by adult bone
marrow stem cell transplants. Six of eight showed relatively normal
immune systems after 1 year.
Reference: Amrolia, P. et al., ``Nonmyeloablative stem cell
transplantation for congenital immunodeficiencies,'' Blood 96,
1239-1246, Aug. 15, 2000.
anemias and other blood conditions
SICKLE CELL ANEMIA
Klein A et al., Hematopoietic stem cell transplantation for severe
sickle cell disease, Rev Med Brux. 2005;26 Spec no:Sp23-5.
Adamkiewicz TV et al., Transplantation of unrelated placental blood
cells in children with high-risk sickle cell disease, Bone Marrow
Transplant. 34, 405-411, Sept 2004.
Wu CJ et al., Molecular assessment of erythroid lineage chimerism
following nonmyeloablative allogeneic stem cell transplantation,
Exp Hematol. 31, 924-933, Oct 2003.
Gore L. et al.; ``Successful cord blood transplantation for sickle cell
anemia from a sibling who is human leukocyte antigen-identical:
implications for comprehensive care,'' J Pediatr Hematol Oncol
22(5):43: -440; Sep-Oct 2000.
Steen RG et al.; ``Improved cerebrovascular patency following therapy
in patients with sickle cell disease: initial results in 4 patients
who received HLA-identical hematopoietic stem cell allografts'';
Ann Neurol 49(2), 222-229; Feb. 2001.
Wethers DL; ``Sickle cell disease in childhood: Part II. Diagnosis and
treatment of major complications and recent advances in
treatment''; Am. Fam. Physician 62, 1309-1314; Sept. 15, 2000.
SIDEROBLASTIC ANEMIA
Ayas M et al.; ``Congenital sideroblastic anaemia successfully treated
using allogeneic stem cell transplantation''; Br J Haematol 113,
938-939; June 2001.
Gonzalez MI et al.; ``Allogeneic peripheral stem cell transplantation
in a case of hereditary sideroblastic anaemia''; British Journal of
Haematology 109, 658-660; 2000.
APLASTIC ANEMIA
Gurman G et al.; ``Allogeneic peripheral blood stem cell
transplantation for severe aplastic anemia''; Ther Apher 5(1), 54-
5: ; Feb. 2001.
Kook H et al.; ``Rubella-associated aplastic anemia treated by
syngeneic stem cell transplantations''; Am. J. Hematol. 64, 303-
305; August 2000.
RED CELL APLASIA
Rabusin M et al.; ``Immunoablation followed by autologous hematopoietic
stem cell infusion for the treatment of severe autoimmune
disease''; Haematologica 85(11 Suppl), 81-85; Nov. 2000.
AMEGAKARYOCYTIC THROMBOCYTOPENIA
Yesilipek et al.; ``Peripheral stem cell transplantation in a child
with amegakaryocytic thrombocytopenia''; Bone Marrow Transplant 26,
5: 1-5: 2; Sept. 2000.
THALASSEMIA
Tan PH et al., ``Unrelated peripheral blood and cord blood
hematopoietic stem cell transplants for thalassemia major,'' Am J
Hematol : 5, 209-212, April 2004.
PRIMARY AMYLOIDOSIS
Sezer 0 et al.; ``Novel approaches to the treatment of primary
amyloidosis''; Exper Opin. Investig. Drugs 9, 2343-2350; Oct 2000.
DIAMOND BLACKFAN ANEMIA
Ostronoff M et al., ``Successful nonmyeloablative bone marrow
transplantation in a corticosteroid-resistant infant with Diamond-
Blackfan anemia,'' Bone Marrow Transplant. 34, 3: 1-3: 2, August
2004.
FANCONI'S ANEMIA
Bitan M et al., Fludarabine-based reduced intensity conditioning for
stem cell transplantation of fanconi anemia patients from fully
matched related and unrelated donors, Biol Blood Marrow Transplant.
12, : 12-: 18, July 2006.
Tan PL et al., Successful engraftment without radiation after
fludarabine-based regimen in Fanconi anemia patients undergoing
genotypically identical donor hematopoietic cell transplantation,
Pediatr Blood Cancer, 46, 630-636, May 1, 2006.
Kohli-Kumar M et al., ``Haemopoietic stem/progenitor cell transplant in
Fanconi anaemia using HLA-matched sibling umbilical cord blood
cells,'' British Journal of Haematology 85, 419-422, October 1993.
CHRONIC EPSTEIN-BARR INFECTION
Fujii N et al.; ``Allogeneic peripheral blood stem cell transplantation
for the treatment of chronic active epstein-barr virus infection'';
Bone Marrow Transplant 26, 805-808; Oct. 2000.
Okamura T et al.; ``Blood stem-cell transplantation for chronic active
Epstein-Barr virus with lymphoproliferation''; Lancet 356, 223-224;
July 2000.
Adult Stem Cells--Repair/Replacement of Solid Tissues
metabolic disorders
HURLER'S SYNDROME
Cox-Brinkman J et al., Haematopoietic cell transplantation (HCT) in
combination with enzyme replacement therapy (ERT) in patients with
Hurler syndrome, Bone Marrow Transplantation 38, 1: -21, 2006.
Staba SL et al., Cord-blood transplants from unrelated donors in
patients with Hurler's syndrome,'' New England Journal of Medicine
350, 1960-1969, 6 May 2004.
Koc ON et al., Allogeneic mesenchymal stem cell infusion for treatment
of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH),
Bone Marrow Transplant 215-222; Aug 2002.
OSTEOGENESIS IMPERFECTA
Horwitz EM et al., ``Isolated allogeneic bone marrow-derived
mesenchymal cells engraft and stimulate growth in children with
osteogenesis imperfecta: Implications for cell therapy of bone,''
Proceedings of the National Academy of Sciences USA 99, 8932-893: ;
25 June 2002.
Horwitz EM et al., ``Clinical responses to bone marrow transplantation
in children with severe osteogenesis imperfecta,'' Blood 9: , 122:
-1231; 1 March 2001.
Horwitz, EM et al.; ``Transplantability and therapeutic effects of bone
marrow-derived mesenchymal cells in children with osteogenesis
imperfecta''; Nat. Med. 5, 309-313; March 1999.
KRABBE LEUKODYSTROPHY
Escolar ML et al., ``Transplantation of umbilical cord-blood in babies
with infantile Krabbe's disease,'' New England Journal of Medicine
352, 2069-2081, 19 May 2005.
Krivit W et al., ``Hematopoietic Stem-Cell Transplantation in Globoid-
Cell Leukodystrophy,'' New England Journal of Medicine 338, 1119-
112: , Apr 16, 1998.
OSTEOPETROSIS
Tsuji Y et al., Successful nonmyeloablative cord blood transplantation
for an infant with malignant infantile osteopetrosis, J Pediatr
Hematol Oncol. 2: , 495-498, Sept. 2005.
Driessen GJ et al., Long-term outcome of haematopoietic stem cell
transplantation in autosomal recessive osteopetrosis: an EBMT
report, Bone Marrow Transplantation 32, 65: -663, October 2003.
Schulz et al., HLA-haploidentical blood progenitor cell transplantation
in osteopetrosis, Blood 99, 3458-3460, 1 May 2002.
CEREBRAL X-LINKED ADRENOLEUKODYSTROPHY
Peters C et al., Cerebral X-linked adrenoleukodystrophy: the
international hematopoietic cell transplantation experience from
1982 to 1999, Blood 104, 881-888, 1 August 2004.
ocular
CORNEAL REGENERATION
Inatomi T et al., Midterm results on ocular surface reconstruction
using cultivated autologous oral mucosal epithelial
transplantation, American Journal of Ophthalmology 141, 26: -2: 5,
February 2006.
Nishida K et al., Corneal reconstruction with tissue-engineered cell
sheets composed of autologous oral mucosal epithelium, New England
Journal of Medicine 351, 118: -1196, 16 September 2004.
Anderson DF et al.; ``Amniotic Membrane Transplantation After the
Primary Surgical Management of Band Keratopathy''; Cornea 20(4),
354-361; May 2001.
Anderson DF et al.; ``Amniotic membrane transplantation for partial
limbal stem cell deficiency''; Br J Ophthalmol 85(5), 56: -5: 5;
May 2001.
Henderson TR et al.; ``The long term outcome of limbal allografts: the
search for surviving cells''; Br J Ophthalmol 85(5), 604-609; May
2001.
Daya SM, Ilari FA; ``Living related conjuctival limbal allograft for
the treatment of stem cell deficiency''; Opthalmology 180, 126-133;
January 2001.
Schwab IR et al.; ``Successful transplantation of bioengineered tissue
replacements in patients with ocular surface disease''; Cornea 19,
421-426; July 2000.
Tsai et al.; ``Reconstruction of damaged corneas by transplantation of
autologous limbal epithelial cells.''; New England Journal of
Medicine 343, 86-93, 2000.
Tsubota K et al.; ``Treatment of severe ocular-surface disorders with
corneal epithelial stem-cell transplantation''; New England Journal
of Medicine 340, 169: -1: 03; June 3, 1999.
wounds & injuries
LIMB GANGRENE
Tateishi-Yuyama E et al.; ``Therapeutic angiogenesis for patients with
limb ischaemia by autologous transplantation of bone-marrow cells:
a pilot study and a randomised controlled trial''; Lancet 360, 42:
-435; 10 August 2002.
SURFACE WOUND HEALING
Badiavas EV and Falanga V, ``Treatment of chronic wounds with bone
marrow-derived cells,'' Archives of Dermatology 139, 510-516, 2003.
JAWBONE REPLACEMENT
Warnke PH et al., Growth and transplantation of a custom vascularised
bone graft in a man, Lancet 364, : 66-: : 0, 28 August 2004.
SKULL BONE REPAIR
Lendeckel S et al., Autologous stem cells (adipose) and fibrin glue
used to treat widespread traumatic calvarial defects: case report,
Journal of Cranio-Maxillofacial Surgery 32, 3: 0-3: 3, 2004.
heart damage
ACUTE HEART DAMAGE
Joseph J et al., Safety and effectiveness of granulocyte-colony
stimulating factor in mobilizing stem cells and improving cytokine
profile in advanced chronic heart failure, American Journal of
Cardiology 9: , 681-684, 1 March 2006.
Blocklet D et al., Myocardial homing of nonmobilized peripheral-blood
CD34+ cells after intracoronary injection, Stem Cells 24, 333-336,
February 2006.
Janssens S et al., Autologous bone marrow-derived stem-cell transfer in
patients with ST-segment elevation myocardial infarction: double-
blind, randomised controlled trial, Lancet 36: , 113-121, 14
January 2006.
Patel AN et al., Surgical treatment for congestive heart failure with
autologous adult stem cell transplantation: a prospective
randomized study, Journal Thoracic Cardiovascular Surgery 130,
1631-1638, December 2005.
Ince H et al., Preservation from left ventricular remodeling by front-
integrated revascularization and stem cell liberation in evolving
acute myocardial infarction by use of granulocyte-colony-
stimulating factor (FIRSTLINE-AMI), Circulation 112, 309: -3106, 15
November 2005.
Ince H et al., Prevention of left ventricular remodeling with
granulocyte colony-stimulating after acute myocardial infarction,
Circulation 112, I-: 3-I-80, 30 August 2005.
Bartunek J et al., Intracoronary injection of CD133-positive enriched
bone marrow progenitor cells promotes cardiac recovery after recent
myocardial infarction, Circulation 112, I-1: 8-I-183, 30 August
2005.
Dohmann HFR et al., Transendocardial autologous bone marrow mononuclear
cell injection in ischemic heart failure, Circulation 112, 121-126,
26 July 2005.
Wollert KC et al., ``Intracoronary autologous bone-marrow cell transfer
after myocardial infarction: the BOOST randomised controlled
clinical trial,'' Lancet 364, 141-148, 10 July 2004.
Britten MB et al., ``Infarct remodeling after intracoronary progenitor
cell treatment in patients with acute myocardial infarction'';
Circulation 108, 2212-2218; Nov 2003.
Perin EC et al.; ``Transendocardial, autologous bone marrow cell
transplantation for severe, chronic ischemic heart failure'';
Circulation 10: , r: 5-r83; published online May 2003.
Stamm C et al.; ``Autologous bone-marrow stem-cell transplantation for
myocardial regeneration''; The Lancet 361, 45-46; 4 January 2003.
Tse H-F et al.; ``Angiogenesis in ischaemic myocardium by
intramyocardial autologous bone marrow mononuclear cell
implantation''; The Lancet 361, 4: -49; 4 January 2003.
Strauer BE et al.; ``Repair of infarcted myocardium by autologous
intracoronary mononuclear bone marrow cell transplantation in
humans''; Circulation 106, 1913-1918; 8 October 2002.
Strauer BE et al.; ``Myocardial regeneration after intracoronary
transplantation of human autologous stem cells following acute
myocardial infarction''; Dtsch Med Wochenschr 126, 932-938; Aug 24,
2001.
Menasche P et al. ``Myoblast transplantation for heart failure.''
Lancet 35: , 2: 9-280; Jan 2: , 2001.
Menasche P et al. [``Autologous skeletal myoblast transplantation for
cardiac insufficiency. First clinical case.''] [article in French]
Arch Mal Coeur Vaiss 94(3), 180-182; March 2001.
CHRONIC CORONARY ARTERY DISEASE
Strauer BE et al., Regeneration of human infarcted heart muscle by
intracoronary autologous bone marrow cell transplantation in
chronic coronary artery disease, Journal of the American College of
Cardiology 46, 1651-1658, 1 November 2005.
neural degenerative diseases & injuries
stroke
Shyu W-C et al., Granulocyte colony-stimulating factor for acute
ischemic stroke: a randomized controlled trial, Canadian Medical
Association Journal 1: 4, 92: -933, 28 March 2006.
Stilley CS et al., Changes in cognitive function after neuronal cell
transplantation for basal ganglia stroke, Neurology 63, 1320-1322,
October 2004.
Meltzer CC et al.; ``Serial [18F]Fluorodeoxyglucose Positron Emission
Tomography after Human Neuronal Implantation for Stroke'';
Neurosurgery 49, 586-592; 2001.
Kondziolka D et al.; ``Transplantation of cultured human neuronal cells
for patients with stroke''; Neurology 55, 565-569; August 2000.
PARKINSON'S DISEASE
Using Direct Stimulation of Patients' Endogenous Adult Neural Stem
Cells
Love S et al., Glial cell line-derived neurotrophic factor induces
neuronal sprouting in human brain, Nature Medicine 11, : 03-: 04,
July 2005.
Slevin JT et al., Improvement of bilateral motor functions in patients
with Parkinson disease through the unilateral intraputaminal
infusion of glial cell line-derived neurotrophic factor, Journal of
Neurosurgery 102, 216-222, February 2005.
Gill SS et al.; ``Direct brain infusion of glial cell line-derived
neurotrophic factor in Parkinson disease''; Nature Medicine 9, 589-
595; May 2003 (published online 31 March 2003).
SPINAL CORD INJURY
Lima C et al., Olfactory mucosa autografts in human spinal cord injury:
A pilot clinical study, Journal of Spinal Cord Medicine 29, 191-
203, July 2006.
liver disease
CHRONIC LIVER DISEASE
Gordon MY et al., Characterisation and clinical application of human
CD34+ stem/progenitor cell populations mobilised into the blood by
G-CSF, Stem Cells 24, 1822-1830, July 2006; published online March
30, 2006.
LIVER CIRRHOSIS
Terai S et al., Improved liver function in liver cirrhosis patients
after autologous bone marrow cell fusion therapy, Stem Cells
published online 15 June 2006; DOI: 10.1634/stemcells.2005-0542.
bladder disease
END-STAGE BLADDER DISEASE
Atala A et al., Tissue-engineered autologous bladders for patients
needing cytoplasty, The Lancet 36: , 1241-1246, 15 April 2006.
______
Response to Questions of Senator Enzi by George Q. Daley, M.D., Ph.D.
Question 1. Professor Daley, sometimes I wonder if we are being
realistic about the short foreseeable advances from stem cell research,
in terms of it always seems medical research is a slow endeavor. For
instance, some adult stem cell therapies have been in commercial
investigation for the past 10 years and not yet reached the market. My
staff reports that there are 1,229 publicly available adult stem cell
trials of which 614 are currently enrolling patients. Are there any
embryonic stem cell therapies that are in early clinical trials now? Do
you have a realistic best case thought when an embryonic stem cell
therapy might be widely used?
Answer 1. Medical research is a slow, methodical, step wise
endeavor to ferret out the biological basis of disease, and to
translate those basic insights into new forms of diagnosis or
treatment. All new medical technologies take years, sometimes decades
to realize their full clinical potential.
Embryonic stem cell research will pay off both in the near term and
the long-term. Near-term, scientists are already using embryonic stem
cells to unravel the secrets of early human development and cell
differentiation--to learn how the cells of the human embryo first
become specialized into nerves, muscle, blood, and more. Such basic
research is certain to yield insights into miscarriage and infertility,
chromosomal abnormalities, intra-uterine growth defects, tissue
generation and regeneration, and cancer. Drugs that are currently being
used clinically are being tested in various in vitro assays that employ
embryonic stem cells, and we might learn that existing drugs can
stimulate stem cell function and encourage tissue repair. In the long-
term, we hope that scientists will learn how to coax embryonic stem
cells to become specific tissues for therapy--skin cells, blood cells,
nerve cells and many others.
It is impossible to predict with any certainty when embryonic stem
cells will themselves serve as a source of specialized cells for cell
replacement therapy. Geron, a leading biotechnology company that has
pioneered embryonic stem cell research, has stated publicly that they
wish to begin human trials of specialized tissues from human embryonic
stem cells for the treatment of spinal cord injury within the next 2
years. My best estimate is that products derived from embryonic stem
cells will be tested in patients within the next 5 to 7 years, but that
effective cell-based therapies cannot be expected for at least a decade
or more.
The history of biomedicine teaches us that most new forms of
therapy take many years to evolve and bear fruit. This was true for the
translation of recombinant DNA into new protein-based drugs (insulin,
interferon, erythropoietin), for monoclonal antibodies, and I believe
will be true for embryonic stem cell-based therapies.
Question 2. Professor Daley, the Administrations current stem cell
policy does not prevent any embryonic stem cell research. Accordingly,
States and private foundations are supporting some research. State
funding alone is expected to add up to several billions of dollars of
funding in the next few years. Accordingly, I noticed some of your work
is supported by private foundations. It seems to me that many of these
foundations that help fund disease research are wonderful drivers of
innovation. Is there anything we can do in Congress to encourage
foundations like those to be created?
Answer 2. Unfortunately, the Administration's current stem cell
policy does indeed effectively prevent an enormous amount of embryonic
stem cell research. Federal funds are essential to virtually every
major biomedical research laboratory, and are used to purchase
equipment and supplies and to pay scientists' salaries. Because no
Federal money can be used for any embryonic stem cell research that
does not narrowly conform to the administration's policy (that is,
purely in vitro research on a small number of lines created prior to
August 9, 2001), any so-called nonconforming ``nonPresidential''
research must be performed with entirely separate equipment and
supplies by personnel whose salary comes from private sources. Because
only a few laboratories and institutions have the resources to
duplicate equipment, space, supplies, and personnel, the vast majority
of American scientists cannot and do not act on the creative
experimental ideas they might have for working in nonconforming areas
of research. The power of the purse is extremely strong, and serves to
limit innovation and intellectual creativity.
State funds and private foundations are not a solution for funding
areas of research that are in the vital national scientific interest.
For scientists outside of a few exclusive States like New Jersey,
Connecticut, and California, no significant alternative funds exist.
Thus the scientists of States like Wyoming and many others are largely
excluded from new and exciting areas of embryonic stem cell science
that fall outside the narrow funding guidelines of the administration
policy. All but a few foundations have endowments large enough to have
a substantive impact on biomedical research, and altogether will not be
able to make up for the absence of funding through the National
Institutes of Health.
Question 3. Professor Daley, as a physician-scientist, do you think
we are doing enough to develop adequate numbers of physician scientists
to fulfill the promise of stem cell research? Can you suggest any
changes we might make to encourage more doctors to pursue innovative
research like you are doing?
Answer 3. The dark storm-clouds over the current NIH funding
climate serve as the greatest hindrance to developing more physician-
scientists. Physician-scientists must train for many years before
achieving independence, and they depend upon Federal grant dollars to
initiate their new research programs. The doubling of the NIH budget
created an enormous new flow of research and allowed for the
development of many new scientists. But given that the NIH budget is no
longer even matching the rising costs due to inflation, everyone's
budgets are being cut across the board, and junior investigators are
being hit the hardest. Moreover, the political controversy over stem
cell research dissuades all but the most idealistic and motivated
scientists from pursuing stem cell research.
Question 4. Dr. Daley, in your research efforts at the Boston
Children's Hospital, you are using embryonic stem cells to replace
problematic genes in certain diseases, such as sickle cell disease and
leukemia. In your estimation, how close are you to a breakthrough that
will improve the health of patients with these diseases?
Answer 4. Our research aims to combine gene therapy and cell
therapy, so that patients with genetic diseases can be treated with
their own genetically-repaired cells in a way that is safe and
effective. We are working on technology platforms that could be applied
to any one of dozens of bone marrow diseases, with sickle cell anemia,
immune deficiency, and leukemia are but a few. We are working
diligently in hopes of achieving breakthroughs that will help improve
the health of my patients. No one knows for certain when breakthroughs
will happen, but in my estimation, I expect to see such advances within
my career, and hopefully within the next decade or two. Basic research
is a long-term investment, but such investments have paid off
handsomely for the United States.
Response to Question of Senator Cochran by George Q. Daley, M.D., Ph.D.
Question. I would address this question to any of our panel members
today, has new scientific research emerged to support or negate the
need for additional embryonic stem cell lines to further your research
efforts?
Answer. I would argue that no research has emerged that would
negate the need for additional embryonic stem cell lines, as the many
so-called ``alternatives'' to embryonic stem cells are not perfect
substitutes. Ample evidence exists and has been published that many of
the current NIH-approved ``Presidential'' embryonic stem cell lines
develop genetic defects when cultured for prolonged periods. This fact
alone argues that a new supply of lines is needed. Moreover, there have
been many new lines established since the administration's policy of
August 9, 2001 was put in place, and many of these new lines have
advantageous properties for stem cell research: for instance, they
carry specific gene defects for human disease, making them extremely
valuable for medical research, or they have been derived under
improved, animal-free conditions that make them particularly favorable
for clinical use.
Repsonse to Question of Senator Enzi by Lauren Stanford
Question. I want to join the other Senators and thank you for
coming here to testify. You are saluted for active participation in the
political process and for raising money for diabetes research. I also
wish you the best of luck in becoming a Senator. What advice would you
have for other teenagers who have been diagnosed with Diabetes?
Answer. I think I would tell other teens with diabetes two things.
First, don't lie to your parents about things like your blood sugars.
If you feel like it's all too much you are better off just telling them
the truth so they can help you. I made that mistake 2 years ago of not
telling them that I was sick of it and not giving myself the insulin I
needed and I almost died. It's better to just be honest and get some
help. Second, I would tell them that their voices are important too.
When we are little kids we all do the diabetes walks and speak up and
all that, but it seems like as soon as a lot of us get to be teens we
stop speaking out. It's hard to be different when you are a teen, but I
think people really listen to us. So keep speaking up about needing a
cure and then you won't have to be sick of diabetes anymore, once it is
cured.
Response to Questions of Senator Enzi by John E. Wagner, Jr., M.D.
Question 1. Professor Wagner, thank you for coming and I wanted to
thank your patients that joined you today. It sounds like you are
making great progress with adult stem cell research. I know you
recognize embryonic stem cell research is important, but do you think
an expansion of adult stem cell research will lead to more therapies in
the next 10 years? Realistically, is there any particular treatments,
other than the ones you are working on, that you are intrigued by and
excited about seeing tried in a clinical setting?
Answer 1. Without question, there are a number of adult stem cell
therapies outside the ones I am working on that are either in the
planning stage or in progress that bear close monitoring. For example,
adult stem cell therapies are being planned for spinal cord injury,
neurodegenerative disease, type I diabetes and vascular injury. Trials
are underway evaluating adult stem cell therapies for acute and chronic
heart failure, bone and joint cartilage repair, and acute brain injury.
However, it must be unequivocally clear that these therapies are as yet
unproven in terms of efficacy. Certainly, the field of adult stem cell
research is extraordinarily exciting and deserves heightened funding in
order to capitalize on its full potential. But, this in no way deters
from the pressing need for greater embryonic stem cell research. ES
cells offer opportunities that are either not possible with adult stem
cells, such as the development of disease specific ES cell lines with
which to identify pathological mechanisms sensitive to novel
pharmacologic agents, or may later prove to be better than adult stem
cells for specific diseases. It is possible, for instance, that ES
cells have a greater capacity to make heart muscle than adult stem
cells. Or, have a greater capacity to make islets for treatment of
diabetes. Also, there may be circumstances that adult stem cells may be
less prone to immune attack, making that a better source for other
diseases. Based on work done at the University of Minnesota and
elsewhere, I believe that we will see major breakthroughs in adult and
embryonic stem cell research over the few years that will lead to an
increasing number of clinical trials.
Question 2. Professor Wagner, we all saw Professor Atala announce
his breakthrough regarding amniotic stem cells and that advance got an
awful lot of press. In addition to your own work, should we expect
other announcements that also have potential to generate new methods of
generating stem cells in the not to distant future?
Answer 2. Professor Atala's report several weeks ago did get a
great deal of press. I know of other research here at the University of
Minnesota and elsewhere specifically evaluating other potential stem
cell sources as well as improved methodologies for isolating and
expanding stem cell populations from umbilical cord blood, the
umbilical cord itself and various adult tissues. However, it is
important to recognize that we do not yet know how the various stem
cell populations compare with each other or whether one source or
isolation/expansion methodology offers a true advantage in terms of
treating patients with disease. All these announcements are exciting
but be very careful about what is in the press as it may not accurately
reflect what is known versus what is pure speculation. As a scientist,
I am asked to speculate as to the meaning of a particular discovery,
but it's just that--speculation. Sometimes, the press may interpret
speculation as fact inappropriately. In my own experience, some have
taken our own discoveries on adult stem cells and used them to nullify
the critical importance of ES cells.
There is purposeful misinformation that scientists, focused on
``finding truth,'' often find themselves too ill-equipped to respond
to. So, while these new discoveries with adult stem cells are
promising, such as that reported by Professor Atala, it is way too
premature to suggest that they replace ES cells in our collective
efforts to reduce suffering and disease.
Question 3. Professor Wagner, I'd like to ask you the same question
I asked Professor Daley, it seems like in order to deliver on the
promise of stem cell research, we need more physician investigators
like yourself. Can you suggest anything Congress should consider to
encourage physicians to pursue the development of innovative therapies
like you have?
Answer 3. It should be clear that we are all devoted to reducing
suffering and minimizing the impact of debilitating diseases, such as
cancer, diabetes, and heart failure. The list of diseases is long and
the number of affected people asking for a chance to live healthy,
productive lives, is enormous. I know that you and others genuinely
want to help us to do just that--the goals are clear and the rewards
will be immeasurable.
First, allow us to pursue all promising avenues. We did this with
cancer and we did this with AIDS. Today, survival rates are the highest
ever. Is there more work to do--obviously, yes. But, the achievements
to date can be attributed to the breadth of the attack. Rather than
limit science, the science was embraced. Rather than limit funding, the
funding was dramatically augmented.
In my opinion, the stem cell and its impact upon science and
medicine will be revolutionary. It promises to fundamentally change the
way we understand disease and the practice of medicine. Just as the
Nation dreamed about the limits of space five decades ago, we dream
about the limits of stem cells today. Could President Kennedy have
imagined the gains we have made in telecommunications when he proposed
the development of NASA? Could he know that there would be a phone at
every ear and GPS device in every car? No. But he did know that space
was worth the investment because the returns 1 day could be
spectacular.
Question 4. What can Congress do to encourage physicians to develop
innovative stem cell therapies?
Answer 4. As a physician, I would start by eliminating the barriers
and provide incentives for collaborations between basic scientists and
clinical investigators and invest in such translational research.
Piecemeal approaches will beget mediocre progress. Substantial and
strategically focused efforts, free of politics, and supportive of both
adult and ES cell basic, translational and clinical research are
required. Right now, the effort is diluted between industry and the
various institutes of the NIH. Just as Congress needs to be united, so
does the NIH. The potential impact of this research is unprecedented
and for that reason, a focused effort is required. Whether this should
manifest itself as a new Institute for Stem Cell Research or as an
additional line item allocation, Congress needs to address the gaps in
the stem cell translational pipeline.
Response to Question of Senator Cochran by John E. Wagner, Jr., M.D.
Question. I would address this question to any of our panel members
today, has new scientific research emerged to support or negate the
need for additional embryonic stem cell lines to further your research
efforts?
Answer. Without a doubt, all stem cell science benefits from the
work we do in any one area. We will never know the full potential of
adult stem cells unless we have the chance to compare them side by side
with embryonic stem cells. Just as we have tested the limits and
possibilities of bone marrow versus cord blood for transplantation, we
must allow the full vetting of the scientific potential of this
science. Indeed, while embryonic stem cells are clearly the ``gold
standard'' against which all other stem cell sources are compared,
today's researchers' hands are tied as the population of embryonic stem
cells available for Federal funding are less than optimal either for
basic research or clinical testing. We need to manufacture new cell
lines that will (1) broaden genetic, racial and ethnic diversity, (2)
be free of animal tissues, and (3) have a defined history both in terms
of proven gamete donor consents as well as reagent exposures and number
of passages. Embryonic stem cell lines and its derivates are more than
simple sources of tissues for repair; they provide us with an
unprecedented resource for understanding mechanisms of disease and
development of targeted treatment strategies to modify or prevent
disease. We have the knowledge and know-how now. While there may be
political reasons, there is absolutely no objective, scientific
research that negates the need for more embryonic stem cell research
and the development of new cell lines. Without question, the
``Presidential'' stem cell lines are suboptimal. Acquisition of genetic
defects after years of passaging in culture and their derivation on
murine feeder layers are two reasons that make them suboptimal. Yet,
these are the only cell lines for which Federal dollars can be used.
Without question, no adult stem cell population, outside the context of
bone marrow transplantation, has any proven efficacy. Certainly, work
is on-going to determine the place of adult stem cells. It is important
to understand that every discovery with embryonic stem cells has only
enhanced our own work with adult stem cells. These facts are
uncontestable!
As proposed by some, why not first determine the true capacity of
adult stem cells and potentially eliminate the ethical issues
associated with embryonic stem cells? The argument has three major
drawbacks: (1) without ES research, how will we ever determine how far
adult stem cells can go in the treatment of disease?; (2) deleterious
impact upon our efficiency in moving stem cell therapies forward; and
(3) without the unbiased pursuit of knowledge, how can science move
forward?
[Whereupon, at 11:41 a.m., the hearing was adjourned.]