[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

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and 
                                Pensions


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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?

                              ----------                              


                        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.

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26. Gorin NC et al.; ``Feasibility and recent improvement of autologous 
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    cells''; Br. J. Haematol. 110, 887-893; Sept 2000.
27. Bruserud 0 et al.; ``New strategies in the treatment of acute 
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28. Laughlin MJ et al.; ``Hematopoietic engraftment and survival in 
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    New England Journal of Medicine 344, 1815-1822; June 14, 2001.
29. Ohnuma K et al.; ``Cord blood transplantation from HLA-mismatched 
    unrelated donors as a treatment for children with haematological 
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30. Ohnuma K et al.; ``Cord blood transplantation from HLA-mismatched 
    unrelated donors as a treatment for children with haematological 
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31. Lindahl J et al.; ``High-dose chemotherapy and APSCT as a potential 
    cure for relapsing hemolysing AILD''; Leuk Res 25(3), 267-270; 
    March 2001.
32. 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.
33. 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 17, 2173-2179; July 1999.
34. 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), 981-987; March 2001.
35. 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, 175-181; Jan 18 2001.
36. 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.
37. 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.
38. 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, 2169-2174; March 15, 
    2000.
39. 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, 307-316; January 2000.
40. Kawa, K et al.; ``Long-Term Survivors of Advanced Neuroblastoma 
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41. Barkholt L et al., Allogeneic haematopoietic stem cell 
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42. Arya M et al., Allogeneic hematopoietic stem-cell transplantation: 
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43. Childs R et al., ``Regression of Metastatic Renal-Cell Carcinoma 
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44. Childs, RW; ``Successful Treatment of Metastatic Renal Cell 
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45. Blay JY et al.; ``High-dose chemotherapy with autologous 
    hematopoietic stem-cell transplantation for advanced soft tissue 
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46. Pedrazolli P et al., High dose chemotherapy with autologous 
    hematopoietic stem cell support for solid tumors other than breast 
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47. 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 27, 959-966; May 2001.
48. Lafay-Cousin L et al.; ``High-dose thiotepa and hematopoietic stem 
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49. Michon, J and Schleiermacher, G. ``Autologous haematopoietic stem 
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50. Schilder, RI et al.; ``Phase I trial of multiple cycles of high-
    dose chemotherapy supported by autologous peripheral-blood stem 
    cells''; J. Clin. Oncol. 17, 2198-2207; July 1999.
51. Anagnostopoulos A et al.; ``High-dose chemotherapy followed by stem 
    cell transplantation in patients with resistant Waldenstrom's 
    macroglobulinemia''; Bone Marrow Transplant 27, 1027-1029; May 
    2001.
52. 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, 3997-3999; Dec 1, 2000.
53. Dispenzieri A et al., Peripheral blood stem cell transplantation in 
    16 patients with POEMS syndrome, and a review of the literature, 
    Blood 104, 3400-3407, 15 November 2004.
54. Burt RK et al., Nonmyeloablative hematopoietic stem cell 
    transplantation for systemic lupus erythematosus, Journal of the 
    American Medical Association 295, 527-535, February 1, 2006.
55. Burt RK et al., ``Induction of tolerance in autoimmune diseases by 
    hematopoietic stem cell transplantation: getting closer to a 
    cure?,'' Blood 99, 768-784, 1 February 2002.
56. Wulffraat NM et al.; ``Prolonged remission without treatment after 
    autologous stem cell transplantation for refractory childhood 
    systemic lupus erythematosus''; Arthritis Rheum 44(3), 728-731; 
    March 2001.
57. 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, 327-336; 
    2000.
58. Traynor AE et al.; ``Treatment of severe systemic lupus 
    erythematosus with high-dose chemotherapy and haemopoietic stem-
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59. Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell 
    Transplantation: A New Therapy for Autoimmune Disease''; Stem 
    Cellsl7, 366-372; 1999.
60. Burt RK et al.; ``Hematopoietic stem cell transplantation of 
    multiple sclerosis, rheumatoid arthritis, and systemic lupus 
    erythematosus''; Cancer Treat. Res. 101, 157-184; 1999.
61. Traynor A and Burt RK; ``Haematopoietic stem cell transplantation 
    for active systemic lupus erythematosus''; Rheumatology 38, 767-
    772; August 1999.
62. Martini A et al.; ``Marked and sustained improvement 2 years after 
    autologous stem cell transplant in a girl with system sclerosis''; 
    Rheumatology 38, 773; August 1999.
63. 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.
64. 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.
65. Passweg, JR et al., Haematopoetic stem cell transplantation for 
    refractory autoimmune cytopenia, British Journal of Haematology 
    125, 749-755, June 2004.
66. 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.
67. A.M. Feasel et al., ``Complete remission of scleromyxedema 
    following autologous stem cell transplantation,'' Archives of 
    Dermatology 137, 1071-1072; Aug. 2001.
68. Burt RK et al., ``Induction of tolerance in autoimmune diseases by 
    hematopoietic stem cell transplantation: getting closer to a 
    cure?,'' Blood 99, 768-784, 1 February 2002.
69. Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell 
    Transplantation: A New Therapy for Autoimmune Disease''; Stem 
    Cellsl7, 366-372; 1999.
70. Kreisel W et al., Complete remission of Crohn's disease after high-
    dose cyclophosphamide and autologous stem cell transplantation, 
    Bone Marrow Transplantation 32, 337-340, 2003.
71. Burt RK et al., ``High-dose immune suppression and autologous 
    hematopoietic stem cell transplantation in refractory Crohn 
    disease,'' Blood 101, 2064-2066, March 2003.
72. 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.
73. Hawkey CJ et al.; ``Stem cell transplantation for inflammatory 
    bowel disease: practical and ethical issues''; Gut 46, 869-872; 
    June 2000.
74. 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.
75. Burt RK et al., ``Induction of tolerance in autoimmune diseases by 
    hematopoietic stem cell transplantation: getting closer to a 
    cure?,'' Blood 99, 768-784, 1 February 2002.
76. Burt RK et al., ``Induction of remission of severe and refractory 
    rheumatoid arthritis by allogeneic mixed chimerism,'' Arthritis & 
    Rheumatism 50, 2466-2470, August 2004.
77. 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), 754-760; April 2001.
78. 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.
79. Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell 
    Transplantation: A New Therapy for Autoimmune Disease''; Stem 
    Cells17, 366-372; 1999.
80. Burt RK et al.; ``Hematopoietic stem cell transplantation of 
    multiple sclerosis, rheumatoid arthritis, and systemic lupus 
    erythematosus''; Cancer Treat. Res. 101, 157-184; 1999.
81. 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.
82. 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.
83. 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.
84. Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell 
    Transplantation: A New Therapy for Autoimmune Disease''; Stem 
    Cellsl7, 366-372; 1999.
85. 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, 2601-2607, 15 March 2005.
86. Burt RK et al., ``Induction of tolerance in autoimmune diseases by 
    hematopoietic stem cell transplantation: getting closer to a 
    cure?,'' Blood 99, 768-784, 1 February 2002.
87. Mancardi GL et al.; ``Autologous hematopoietic stem cell 
    transplantation suppresses Gd-enhanced MRI activity in MS''; 
    Neurology 57, 62-68; July 10, 2001.
88. 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.
89. Burt, RK and Traynor, AE; ``Hematopoietic Stem Cell 
    Transplantation: A New Therapy for Autoimmune Disease''; Stem 
    Cellsl7, 366-372; 1999.
90. Burt RK et al.; ``Hematopoietic stem cell transplantation of 
    multiple sclerosis, rheumatoid arthritis, and systemic lupus 
    erythematosus''; Cancer Treat. Res. 101, 157-184; 1999.
91. 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, 327-336; 
    2000.
92. 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.
93. Seifert B et al., Complete remission of alopecia universalis after 
    allogeneic hematopoietic stem cell transplantion, Blood 105, 426-
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94. Grunebaum E et al., Bone marrow transplantation for severe combined 
    immune deficiency, Journal of the American Medical Association 295, 
    508-518, 1 February 2006.
95. Cavazzana-Calvo M et al.; ``Gene therapy of human severe combined 
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    28, 2000. (NOTE: gene therapy using bone marrow adult stem cells as 
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96. Ziegner UH et al.; ``Unrelated umbilical cord stem cell 
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97. Amrolia, P. et al., ``Nonmyeloablative stem cell transplantation 
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98. Klein A et al., Hematopoietic stem cell transplantation for severe 
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99. 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.
100. Wu CJ et al., Molecular assessment of erythroid lineage chimerism 
    following nonmyeloablative allogeneic stem cell transplantation, 
    Exp Hematol. 31, 924-933, Oct 2003.
101. 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):437-440; Sep-Oct 2000.
102. Steen RG et al.; ``Improved cerebrovascular patency following 
    therapy in patients with sickle cell disease: initial results in 4 
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103. 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.
104. Ayas M et al.; ``Congenital sideroblastic anaemia successfully 
    treated using allogeneic stem cell transplantation''; Br J Haematol 
    113, 938-939; June 2001.
105. Gonzalez MI et al.; ``Allogeneic peripheral stem cell 
    transplantation in a case of hereditary sideroblastic anaemia''; 
    British Journal of Haematology 109, 658-660; 2000.
106. Gurman G et al.; ``Allogeneic peripheral blood stem cell 
    transplantation for severe aplastic anemia''; Ther Apher 5(1), 54-
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107. Kook H et al.; ``Rubella-associated aplastic anemia treated by 
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    305; August 2000.
108. 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.
109. Yesilipek et al.; ``Peripheral stem cell transplantation in a 
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110. Tan PH et al., ``Unrelated peripheral blood and cord blood 
    hematopoietic stem cell transplants for thalassemia major,'' Am J 
    Hematol 75, 209-212, April 2004.
111. Sezer O et al.; ``Novel approaches to the treatment of primary 
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112. Ostronoff M et al., ``Successful nonmyeloablative bone marrow 
    transplantation in a corticosteroid-resistant infant with Diamond-
    Blackfan anemia,'' Bone Marrow Transplant. 34, 371-372, August 
    2004.
113. 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, 712-718, July 2006.
114. Tan PL et al., Successful engraftment without radiation after 
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    genotypically identical donor hematopoietic cell transplantation, 
    Pediatr Blood Cancer, 46, 630-636, May 1, 2006.
115. 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, 
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116. 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.
117. Okamura T et al.; ``Blood stem-cell transplantation for chronic 
    active Epstein-Barr virus with lymphoproliferation''; Lancet 356, 
    223-224; July 2000.
118. 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, 17-21, 2006.
119. 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.
120. 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.
121. 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, 8932-8937; 
    25 June 2002.
122. Horwitz EM et al., ``Clinical responses to bone marrow 
    transplantation in children with severe osteogenesis imperfecta,'' 
    Blood 97, 1227-1231; 1 March 2001.
123. 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.
124. 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.
125. Krivit W et al., ``Hematopoietic Stem-Cell Transplantation in 
    Globoid-Cell Leukodystrophy,'' New England Journal of Medicine 338, 
    1119-1127, Apr 16, 1998.
126. Tsuji Y et al., Successful nonmyeloablative cord blood 
    transplantation for an infant with malignant infantile 
    osteopetrosis, J Pediatr Hematol Oncol. 27, 495-498, Sept 2005.
127. Driessen GJ et al., Long-term outcome of haematopoietic stem cell 
    transplantation in autosomal recessive osteopetrosis: an EBMT 
    report, Bone Marrow Transplantation 32, 657-663, October 2003.
128. Schulz et al., HLA-haploidentical blood progenitor cell 
    transplantation in osteopetrosis, Blood 99, 3458-3460, 1 May 2002.
129. 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.
130. Inatomi T et al., Midterm results on ocular surface reconstruction 
    using cultivated autologous oral mucosal epithelial 
    transplantation, American Journal of Ophthalmology 141, 267-275, 
    February 2006.
131. Nishida K et al., Corneal reconstruction with tissue-engineered 
    cell sheets composed of autologous oral mucosal epithelium, New 
    England Journal of Medicine 351, 1187-1196, 16 September 2004.
132. Anderson DF et al.; ``Amniotic Membrane Transplantation After the 
    Primary Surgical Management of Band Keratopathy''; Cornea 20(4), 
    354-361; May 2001.
133. Anderson DF et al.; ``Amniotic membrane transplantation for 
    partial limbal stem cell deficiency''; Br J Ophthalmol 85(5), 567-
    575; May 2001.
134. 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.
135. Daya SM, Ilari FA; ``Living related conjuctival limbal allograft 
    for the treatment of stem cell deficiency''; Opthalmology 180, 126-
    133; January 2001.
136. Schwab IR et al.; ``Successful transplantation of bioengineered 
    tissue replacements in patients with ocular surface disease''; 
    Cornea 19, 421-426; July 2000.
137. Tsai et al.; ``Reconstruction of damaged corneas by 
    transplantation of autologous limbal epithelial cells.''; New 
    England Journal of Medicine 343, 86-93, 2000.
138. Tsubota K et al.; ``Treatment of severe ocular-surface disorders 
    with corneal epithelial stem-cell transplantation''; New England 
    Journal of Medicine 340, 1697-1703; June 3, 1999.
139. 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, 427-435; 10 August 2002.
140. Badiavas EV and Falanga V, ``Treatment of chronic wounds with bone 
    marrow-derived cells,'' Archives of Dermatology 139, 510-516, 2003.
141. Warnke PH et al., Growth and transplantation of a custom 
    vascularised bone graft in a man, Lancet 364, 766-770, 28 August 
    2004.
142. 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, 370-373, 2004.
143. 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 97, 681-684, 1 March 2006.
144. Blocklet D et al., Myocardial homing of nonmobilized peripheral-
    blood CD34+ cells after intracoronary injection, Stem Cells 24, 
    333-336, February 2006.
145. 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 367, 
    113-121, 14 January 2006.
146. 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.
147. 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, 3097-3106, 15 
    November 2005.
148. Ince H et al., Prevention of left ventricular remodeling with 
    granulocyte colony-stimulating after acute myocardial infarction, 
    Circulation 112, I-73-1-80, 30 August 2005.
149. Bartunek J et al., Intracoronary injection of CD133-positive 
    enriched bone marrow progenitor cells promotes cardiac recovery 
    after recent myocardial infarction, Circulation 112, I-178-I-183, 
    30 August 2005.
150. Dohmann HFR et al., Transendocardial autologous bone marrow 
    mononuclear cell injection in ischemic heart failure, Circulation 
    112, 121-126, 26 July 2005.
151. 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.
152. Britten MB et al., ``Infarct remodeling after intracoronary 
    progenitor cell treatment in patients with acute myocardial 
    infarction''; Circulation 108, 2212-2218; Nov 2003.
153. Perin EC et al.; ``Transendocardial, autologous bone marrow cell 
    transplantation for severe, chronic ischemic heart failure''; 
    Circulation 107, r75-r83; published online May 2003.
154. Stamm C et al.; ``Autologous bone-marrow stem-cell transplantation 
    for myocardial regeneration''; The Lancet 361, 45-46; 4 January 
    2003.
155. Tse H-F et al.; ``Angiogenesis in ischaemic myocardium by 
    intramyocardial autologous bone marrow mononuclear cell 
    implantation''; The Lancet 361, 47-49; 4 January 2003.
156. 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.
157. 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.
158. Menasche P et al. ``Myoblast transplantation for heart failure.'' 
    Lancet 357, 279-280; Jan 27, 2001.
159. 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.
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.]

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