[Senate Hearing 108-949]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 108-949

 
                  ADVANCES IN ADULT AND NON-EMBRYONIC 
                           STEM CELL RESEARCH

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

                                HEARING

                               before the

                 SUBCOMMITTEE ON SCIENCE, TECHNOLOGY, 
                               AND SPACE

                                 of the

                         COMMITTEE ON COMMERCE,
                      SCIENCE, AND TRANSPORTATION
                          UNITED STATES SENATE

                      ONE HUNDRED EIGHTH CONGRESS

                             FIRST SESSION

                               __________

                             JUNE 12, 2003

                               __________

    Printed for the use of the Committee on Commerce, Science, and 
                             Transportation



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       SENATE COMMITTEE ON COMMERCE, SCIENCE, AND TRANSPORTATION

                      ONE HUNDRED EIGHTH CONGRESS

                             FIRST SESSION

                     JOHN McCAIN, Arizona, Chairman
TED STEVENS, Alaska                  ERNEST F. HOLLINGS, South 
CONRAD BURNS, Montana                    Carolina, Ranking
TRENT LOTT, Mississippi              DANIEL K. INOUYE, Hawaii
KAY BAILEY HUTCHISON, Texas          JOHN D. ROCKEFELLER IV, West 
OLYMPIA J. SNOWE, Maine                  Virginia
SAM BROWNBACK, Kansas                JOHN F. KERRY, Massachusetts
GORDON H. SMITH, Oregon              JOHN B. BREAUX, Louisiana
PETER G. FITZGERALD, Illinois        BYRON L. DORGAN, North Dakota
JOHN ENSIGN, Nevada                  RON WYDEN, Oregon
GEORGE ALLEN, Virginia               BARBARA BOXER, California
JOHN E. SUNUNU, New Hampshire        BILL NELSON, Florida
                                     MARIA CANTWELL, Washington
                                     FRANK R. LAUTENBERG, New Jersey
      Jeanne Bumpus, Republican Staff Director and General Counsel
             Robert W. Chamberlin, Republican Chief Counsel
      Kevin D. Kayes, Democratic Staff Director and Chief Counsel
                Gregg Elias, Democratic General Counsel
                                 ------                                

             SUBCOMMITTEE ON SCIENCE, TECHNOLOGY, AND SPACE

                    SAM BROWNBACK, Kansas, Chairman
TED STEVENS, Alaska                  JOHN B. BREAUX, Louisiana, Ranking
CONRAD BURNS, Montana                JOHN D. ROCKEFELLER IV, West 
TRENT LOTT, Mississippi                  Virginia
KAY BAILEY HUTCHISON, Texas          JOHN F. KERRY, Massachusetts
JOHN ENSIGN, Nevada                  BYRON L. DORGAN, North Dakota
GEORGE ALLEN, Virginia               RON WYDEN, Oregon
JOHN E. SUNUNU, New Hampshire        BILL NELSON, Florida
                                     FRANK R. LAUTENBERG, New Jersey


                            C O N T E N T S

                              ----------                              
                                                                   Page
Hearing held on June 12, 2003....................................     1
Statement of Senator Brownback...................................     1
    Prepared statement...........................................     2

                               Witnesses

Barsh, Steven L., Merion Station, Pennsylvania...................    40
    Prepared statement...........................................    42
Hess, David C., Professor and Chairman, Department of Neurology, 
  Medical College of Georgia.....................................     3
    Prepared statement...........................................     6
Kurtzberg, M.D., Joanne, Director, Pediatric Stem Cell Transplant 
  Program, Duke University Medical Center........................    11
    Prepared statement...........................................    15
McDonald, M.D., Ph.D., John, on behalf of the Coalition for the 
  Advancement of Medical Research................................    23
    Prepared statement...........................................    25
Peduzzi-Nelson, Ph.D., Jean D., Department of Physiological 
  Optics, University of Alabama at Birmingham....................    26
    Prepared statement...........................................    28
Penn, Keone, Snellville, Georgia.................................    47
    Prepared statement...........................................    48
Rubinstein, M.D., Pablo, Director of Placental Blood Program, New 
  York Blood Center..............................................     9
    Prepared statement...........................................    15
Sprague, Stephen R., Staten Island, New York.....................    44
    Prepared statement...........................................    45

                                Appendix

Testimony of the American Academy of Physician Assistants........    55


         ADVANCES IN ADULT AND NON-EMBRYONIC STEM CELL RESEARCH

                              ----------                              


                        THURSDAY, JUNE 12, 2003,

                               U.S. Senate,
    Subcommittee on Science, Technology, and Space,
        Committee on Commerce, Science, and Transportation,
                                                    Washington, DC.
    The Subcommittee met, pursuant to notice, at 2:46 p.m. in 
room SR-253, Russell Senate Office Building, Hon. Sam 
Brownback, Chairman of the Subcommittee, presiding.

           OPENING STATEMENT OF HON. SAM BROWNBACK, 
                    U.S. SENATOR FROM KANSAS

    Senator Brownback. The hearing will come to order. I want 
to thank everybody for being here today, particularly the 
witnesses that traveled some distance. We have a couple of 
really special ones--not that all of you aren't special, but I 
think you're going to find these just particularly heartening 
stories of incredible things that have taken place.
    Today, we'll be conducting a hearing on some of the 
exciting new advances being made in the fields of adult and 
non-embryonic stem cell research. As I'm sure many of you know, 
the field of regenerative medicine offers great hope to those 
suffering from this disease. Much of the research that is 
providing new hope to those who are currently suffering is 
moving along at a fast pace and is doing so without 
questionable or morally controversial techniques.
    At this hearing, we will examine some of these advances. 
This hearing is not about human cloning or destructive human 
embryonic stem cell research. Rather, it is about some of the 
other important scientific discoveries that are being made 
using noncontroversial techniques that rely on adult or non-
embryonic stem cells. And these are some processes that only a 
year-and-a-half ago, we'll recall, were being called ``junk 
science.'' And yet you're going to hear today from people that 
have been cured. So there's been amazing work, fabulous work, 
that has really resulted in people's lives being changed.
    In particular today, we will hear from cord-blood stem cell 
researchers, as well as others, who are working hard in the 
field of regenerative medicine to find the cures to the 
diseases that plague humanity. At this hearing, we will discuss 
not only some of the research that is being conducted, but also 
some of the treatments that are currently being offered. And we 
will hear from some of the patients who are benefiting from 
this important life-saving research. The stories that we will 
hear from some of the patients will truly be astounding. They 
are miraculous. We all agree on the need to work hard toward a 
cure for the diseases that plague humanity, and we're going to 
be listening to some of that success here today.
    Now, rather than discussing this, I'd like to take 
advantage of the panels that we have here today to testify. I 
want to turn to our first panel of people to testify. And they 
are Dr. David Hess, M.D., Chairman and Professor, Department of 
Neurology, Medical College of Georgia, in Augusta, Georgia; Dr. 
Joanne Kurtzberg, M.D., Director of the Pediatric Stem Cell 
Transplant Program at Duke University Medical Center, in 
Durham, North Carolina--being a KU grad, I'm familiar with 
Duke----
    [Laughter.]
    Senator Brownback.--and a very good school, other than in 
basketball----
    [Laughter.]
    Senator Brownback.--Dr. John W. McDonald, M.D., Ph.D., 
Washington University School of Medicine, Department of 
Neurology, in St. Louis, Missouri; Dr. Jean Peduzzi-Nelson, 
Ph.D., University of Alabama at Birmingham; and Dr. Pablo 
Rubinstein, M.D., Director of Placental Blood Program, New York 
Blood Center, New York, New York.
    I'm delighted to have such a distinguished panel here with 
us today to testify. I look forward to your testimony. If you 
would, we will run the clock on 7 minutes. We will take your 
full testimony into the record. I think it's always best for 
people to summarize somewhat in putting it forward, so it can 
save time, as well, for questions afterwards.
    We do have an active floor running today. We may have to 
have recesses periodically, for me to go over and vote. Other 
members will probably be joining us, as well, so there may be 
some people stepping in.
    [The prepared statement of Senator Brownback follows:]

   Prepared Statement of Hon. Sam Brownback, U.S. Senator from Kansas

    Thank you for coming to our hearing today.
    Today, we will be conducting a hearing on some of the exciting new 
advances being made in the fields of adult and non-embryonic stem cell 
research.
    As I am sure many of you here know, the field of regenerative 
medicine offers great hope to those suffering from disease. Much of the 
research that is providing new hope to those who are currently 
suffering is moving along at a fast pace and is doing so without 
questionable or morally controversial techniques.
    At this hearing we will examine some of these advances.
    This hearing is not about human cloning, or destructive human 
embryonic stem cell research.
    Rather, it is about some of the other important scientific 
discoveries that are being made using non-controversial techniques that 
rely on adult or non-embryonic stem cells.
    In particular, today we will hear from cord blood stem cell 
researchers as well as others who are working hard in the field of 
regenerative medicine to find the cures to the diseases that plague 
humanity.
    At this hearing we will discuss not only some of the research that 
is being conducted but also some of the treatments that are currently 
being offered.
    And, we will hear from some of the patients who are benefitting 
from this important life-saving research. The stories that we will hear 
from some of the patients will truly be astounding.
    Regardless of how the members of this committee feel on the 
controversial issues of human cloning and destructive human embryonic 
stem cell research, certainly, we can all agree on the need to work 
hard toward a cure for the diseases that plague humanity.
    Now, rather than describe some of the advances being made I would 
like to turn to our first panel.

    Senator Brownback.With that, Dr. Hess, I'd like to invite 
your testimony, and we will move on down this panel list.

STATEMENT OF DAVID C. HESS, PROFESSOR AND CHAIRMAN, DEPARTMENT 
            OF NEUROLOGY, MEDICAL COLLEGE OF GEORGIA

    Dr. Hess. Thank you, Senator Brownback.
    I'm David C. Hess. I'm Professor and Chairman of the 
Department of Neurology at the Medical College of Georgia. I am 
a physician and neurologist, and that's a specialist that cares 
for people with neurological diseases.
    Many neurological diseases, such as strokes, spinal-cord 
injury, Alzheimer's disease, Parkinson's disease, and Lou 
Gehrig's disease, are formidable foes, resistant to treatment, 
and take an enormous toll in suffering, like you mentioned. A 
week will not pass when I do not receive an e-mail or a call 
from a suffering patient asking for a stem cell injection to 
help them recover their ability to walk or to speak. Some 
patients are so desperate that they offer up themselves to be 
the first patient to try the stem cells. I can't blame them. 
There are few effective treatments for their diseases, and they 
are looking for any ray of hope.
    As you mentioned, Senator Brownback, there is some 
foundation for their hope. The field of regenerative medicine 
is taking off, and there are new regenerative-medicine and stem 
cell institutes and centers being established all over the 
country.
    Many scientific dogma have been slain in the past 5 years. 
One dogma was that we don't make new brain cells in our brain, 
in adults. In other words, you steadily lose what you have. 
However, in a set of clever experiments, it has recently been 
shown that humans, even in their 60s and 70s, can make new 
nerve cells in their hippocampus, a comforting fact for all of 
us.
    Adult stem cells can be obtained from a variety of organs, 
ranging from the brain's so-called neural stem cells to the 
skin. However, the best study is that most accessible adult 
stem cells are in the bone marrow. Bone marrow is a rich source 
of stem and progenitor cells. I will briefly review the 
potential of adult stem cells derived from the bone marrow.
    As a physician, my motivation is to see some of these cells 
used to treat these devastating neurological diseases that I 
see every day. And as a physician researcher, I'm trying to 
make some small contribution to the stroke-recovery field, 
thanks to past support from the American Heart Association and, 
presently, the NIH.
    Let me explain. Bone marrow contains two major types of 
stem or progenitor cells, and maybe many more. The two major 
types are the hematopoietic stem cells and the mesenchymal stem 
cells, or what are often called marrow stromal cells.
    Hematopoietic stem cells have been used for years in bone-
marrow transplants and have cured thousands of patients with 
leukemias and other forms of cancer. These hematopoietic stem 
cells have the ability to circulate throughout the whole body 
and reach every organ in the body. Their plasticity--that is, 
their ability to turn into other cell types of cells, such as 
nerve cells, liver cells, and pancreas cells that produce 
insulin--is still hotly debated; however, there is evidence 
that these cells can turn into Purkinje cells in the brain, a 
very sophisticated type of nerve cell. And this phenomena is 
not just restricted to rodents. There is now autopsy evidence 
from humans that bone-marrow cells can form new neurons in the 
brain. There may also be other bone-marrow-derived cells that 
circulate in the peripheral blood, with stem cell or progenitor 
cell qualities.
    Recently, the progeny, or the daughter, of the 
hematopoietic stem cell, so to speak, circulating blood 
monocytes, have been shown to be able to differentiate into 
nerve cells and blood-vessel cells called endothelial cells. 
This is potentially of great clinical relevance, as monocytes 
are easy to isolate from human blood and could be a rich source 
of replacement cells.
    There are also bone-marrow cells that do not normally 
circulate in the bloodstream, but, instead, reside in the bone 
marrow and service supporting cells for the hematopoietic stem 
cells. These cells are called mesenchymal stem cells, or marrow 
stromal cells. It is these cells that are the source of much 
excitement in the field of regenerative medicine.
    Some of the most exciting research, in terms of an eventual 
human clinical application, are the multipotent adult 
progenitor cells isolated by Catherine Verfaillie. These can be 
isolated from both rodent and human bone marrow. They are able 
to turn into cells of all three germ layers. That is, they can 
turn into endothelial cells, which line the blood vessels, 
liver cells, and nerve cells. And, importantly, they don't just 
do this in a petri dish; they are also able to do it in the 
live animal. Moreover, they do not die prematurely, and, 
importantly, they do not form teratomas, or tumors, like 
embryonic stem cells tend to do.
    Dr. Walter Low, a collaborator of Dr. Verfaillie, has 
recently shown that these MAPCs can aid in brain repair after 
stroke in a rodent. The obvious advantage of these cells for 
regenerative medicine is that they can be easily isolated from 
human bone marrow and the potential for a patient to be cured 
or treated with their own cells, without any fear of rejection.
    A closely related cell type is the marrow stromal cell. 
Marrow stromal cells have been shown to be involved in brain 
repair after stroke and traumatic brain injury, by Dr. Michael 
Chopp, at Henry Ford Hospital, and to repair the injured spinal 
cord, by Dr. Darwin Prockop's group at Tulane. Like many other 
adult stem cells, these cells can be delivered intravenously, 
and they can home to the injured tissue, almost like a guided 
missile. There appear to be chemical signals released by 
injured tissue that attract these cells. Marrow stromal cells 
are easy to culture, easy to expand; and, since they can be 
autologous, they would not be rejected.
    How, exactly, these cells repair injured tissue is not 
clear. While, in some cases, there is actual replacement of 
injured cells, it seems more likely that these cells serve as 
growth-factor factories and aid the tissue to repair itself.
    There's also another type of circulating bone-marrow-
derived cell, the so-called endothelial progenitor cell that 
has attracted much recent interest. EPCs circulate in the 
bloodstream and form new endothelial cells in blood vessels. We 
now know that these EPCs contribute to organ repair after 
cutting off blood supply to the heart, the limbs, and the 
brain. This is critically important, as cardiovascular disease 
and stroke are two of the three biggest killers in the United 
States. We have learned that by giving animals extra doses of 
these EPCs, we can improve their outcome from heart attack and 
salvage their limbs that are starved for blood.
    The field is moving very, very fast. Bone-marrow-derived 
cells are already being tested in small numbers of patients 
with heart attacks. The TOPCARE trial was a trial published in 
the journal, The Lancet. And, in this, bone-marrow cells, 
harvested from the patient's own bone marrow or their blood, 
were delivered via a catheter in the coronary artery to these 
patients. The procedure was safe, and the initial results were 
encouraging, though this was a very small trial.
    Another type of bone-marrow blood stem cell, which you're 
going to hear about later, is the human umbilical cord stem 
cell. These are derived from umbilical cords that are normally 
discarded after a delivery. Umbilical cord blood is a rich 
source of stem cells. These have already been exploited as a 
source of bone-marrow transplants in the cancer field and in 
sickle-cell anemia.
    These umbilical cord stem cells also have great potential 
as a treatment for neurological disease. When delivered 
intravenously to a rodent with a stroke, they help improve the 
outcome of that stroke in that rodent.
    Despite these hopeful signs, much work needs to be done. 
Before we are able to treat humans safely and effectively, we 
need to define the optimal dosing of these cells, the optimal 
type of bone-marrow populations to use, and the timing of when 
to administer them. And then how should we administer them? 
Should we give them directly into the tissue, like into the 
heart or the brain? Should we deliver them intravenously, or 
should we give them in an artery? There's multiple avenues that 
we could give them. We also need to learn more about how these 
bone-marrow cells and other adult stem cells home or go to the 
damaged tissue.
    The major advantages of bone-marrow-derived stem cells are 
that they are autologous, with the exception of umbilical cord 
stem cells, and, therefore, they are less likely to be 
rejected. They can be easily isolated from bone-marrow 
aspirates, which are done clinically, and they avoid the 
ethical concerns that many have with embryonic stem cells.
    However, we have to keep in mind that repairing the central 
nervous system is a daunting task. Neurons make tens of 
thousands of connections with other nerve cells. Some of them 
send projections, or axons, from meters--feet, literally--and 
it's very important that they connect up to the other cell.
    In most of the experiments, so far, we have little evidence 
that any stem cell delivered into an adult will be able to make 
all these connections and become fully functional. It is likely 
that most of the cell transplants in the brain work by 
stimulating the brain to actually repair itself. We need to 
learn more about enhancing these self-repair processes.
    In the growing field of cell therapy, we will need to 
target diseases with specific cell types and approaches. One 
size will not fit all. We may need to treat some of these 
diseases with a combination of both cells and different growth 
factors. The treatments we develop for Parkinson's disease will 
probably be vastly different from those we develop for stroke. 
There are no magic bullets; only painstaking research and more 
funding will allow us to advance.
    Thank you.
    [The prepared statement of Dr. Hess follows:]

Prepared Statement of David C. Hess, Professor and Chairman, Department 
                of Neurology, Medical College of Georgia

    I am David C. Hess M.D., Professor and Chairman of the Department 
of Neurology at the Medical College of Georgia. I am a physician and 
neurologist, a specialist that cares for people with neurological 
diseases. Many neurological diseases such as stroke, spinal cord 
injury, Alzheimer's disease, Parkinson's disease, and Amyotrophic 
Lateral Sclerosis (Lou Gehrig's disease) are formidable foes, resistant 
to treatment and take an enormous toll in suffering. A week will not 
pass when I do not receive an e-mail or a call from a suffering patient 
asking for a stem cell injection to help them recover their ability to 
walk or speak.. Some patients are so desperate that they offer up 
themselves to be the first patient to try the stem cells. I can't blame 
them; there are few effective treatment for their diseases and they are 
looking for any ray of hope. They have also been influenced by 
exaggerations in the media.
    Yet there is some foundation to their hope. The field of 
``regenerative medicine'' is taking off and there are new 
``Regenerative Medicine'' and ``Stem Cell'' institutes and centers 
being established all over the country. Many scientific dogma have been 
slain in the past 5 years. One dogma was that new neurons are not born 
in the brains of humans-in other words, you just steadily lose what you 
have as you age. However, in a set of clever experiments by Drs. 
Ericksson and Gage in1998 it was shown that humans even in their 60s 
can make new nerve cells in their hippocampus, a comforting fact for 
all of us. Moreover, mice make more new neurons if they are kept in an 
``enriched'' environment and exercise (Kempermann, 2002). If we can 
extrapolate these findings to humans, it suggests that by keeping our 
minds active we are less likely to lose them. We also now know that new 
neurons can be made in response to a brain injury in other parts of the 
rodent brain, not just the hippocampus. For example, after a stroke, 
new neurons are born and travel to the damaged tissue and appear to aid 
in its repair (Arvidsson, 2002). Now we have to learn how to enhance 
and stimulate these natural repair mechanisms.
    Adult stem cells can be obtained from a variety of organs ranging 
from the brain (so called neural stem cells) to the skin. However, the 
best studied and most accessible adult stem cells are in the bone 
marrow. Bone marrow is a rich source of stem and progenitor cells. I 
will briefly review the potential of adult or non-embryonic stem cells 
to treat human disease. I will focus on bone marrow stem cells. As a 
physician my perspective is on the clinical potential of these advances 
and my motivation is to see some of these cells used to treat these 
devastating neurological diseases that I see every day. As a physician-
researcher, I am trying to make some small contributions to the stroke 
recovery field thanks to past support from the American Heart 
Association and currently the NIH.
    Bone marrow contains two major types of stem or progenitor cells 
and maybe many more. The two major types are the hematopoietic stem 
cells and the mesenchymal stem cells or marrow stromal cells. 
Hematopoieitc stem cells have been used for years in bone marrow 
transplants and have cured thousands of patients with leukemias and 
other forms of cancer. These hematopoietic stem cells and their 
progeny-the white blood cells, red blood cells and platelets-have the 
ability to circulate throughout the bloodstream and reach every organ 
in the body. Their plasticity, that is, the ability of these cells to 
``turn ``into other cell types such as nerve cells, liver cells and 
pancreas cells that produce insulin, is still hotly debated. However, 
there is evidence that these cells can rarely differentiate into 
Purkinje cells in the brain, a very sophisticated type of neuron. The 
phenomenon is not restricted to rodents; there is now autopsy evidence 
from humans that bone marrow cells are involved in the formation of 
neurons at a low level (Mezey, 2003)
    Some recent evidence had suggested that cell fusion was responsible 
for some of the plasticity that had been described for bone marrow stem 
cells (Terada, 2002; Wang, 2003; Vassilopoulos, 2003). In cell fusion, 
the bone marrow cells would not actually ``turn into'' another cell 
type-they would just fuse with the mature cell giving it twice the 
number of chromosomes and thereby making it potentially unstable. 
However, while cell fusion may indeed account for some of the 
``plasticity'' of bone marrow cells, particularly in the liver, it does 
not seem to account for all of it. In recent work, bone marrow cells 
have been shown to become functional insulin-secreting cells in the 
pancreas of mice without any evidence of cell fusion (Ianus, 2003).
    There may also be bone marrow-derived cells that circulate in the 
peripheral blood with ``stem cell'' or ``progenitor cell'' qualities. 
Recently the progeny of the hematopoietic stem cell, a subpopulation of 
circulating blood monocytes, have been shown to be able to 
differentiate into nerve cells and blood vessel cells called 
endothelial cells (Zhao, 2003). This is potentially of great clinical 
relevance as monocytes are easy to isolate from human blood and could 
be a rich source of replacement cells.
    There are also bone marrow cells that do not normally circulate in 
the bloodstream but instead reside in the bone marrow and serve as 
supporting cells for the hematopoietic stem cells. These cells are 
called mesenchymal stem cells or marrow stromal cells. It is these 
cells that are the source of much excitement in the field of 
regenerative medicine. Some of the most exciting research, in terms of 
an eventual human clinical application, are the Multipotent adult 
progenitor cells (MAPC) isolated by Catherine Verfailie and described 
comprehensively in the July 2002 issue of Nature (Jiang, 2002). These 
cells can be isolated from rodent and human bone marrow. They are able 
to differentiate into cells of all three germ layers (endoderm, 
mesoderm and ectoderm) that is they can from endothelial cells or blood 
vessel lining cells, hepatocytes (liver cells), and nerve cells. They 
not only do this in the petri dish, they also do it in the live animal. 
Moreover, they do not senesce or die prematurely and importantly they 
do not form teratomas or tumors like embryonic stem cells tend to do. 
Dr. Walter Low a collaborater of Dr. Verfaillie has shown that these 
MAPCS can aid in brain repair after stroke in a rodent (Zhao, 2002). 
The obvious advantages of these cells for regenerative medicine is 
their easy isolation from human bone marrow and the potential for a 
patient to be their own donor without fear of rejection.
    A closely related cell type is the marrow stromal cell. Marrow 
stromal cells have been shown to be involved in brain repair after 
stroke and traumatic brain injury by Dr. Chopp at Henry Ford Hospital 
and to repair the injured spinal by Dr. Darwin Prockop's group at 
Tulane. Like many other adult stem cells, these cells can be delivered 
intravenously and then ``home'' like a guided missile to the injured 
tissue. There are chemical signals released by injured tissue that 
attract these cells. Marrow stromal cells are easy to culture, easy to 
expand, and since they are autologous they would not be rejected. How 
exactly these cells repair injured tissue is not clear. While in some 
cases this is actual replacement of damaged cells, it seems more likely 
that these cells serve as growth factor ``factories'' and aid the 
tissue to repair itself by reactivating latent developmental programs.
    There is also another type of circulating bone marrow-derived cell, 
the endothelial progenitor cell (EPC) that has also attracted much 
recent interest. Endothelial cells are cells that line all the blood 
vessels of the body. Besides being mere conduits for blood, we now know 
that they play an active and necessary role in the development and 
sustenance of the body's organs. Bone marrow cells that can circulate 
in the bloodstream and form new endothelial cells and blood vessels 
were first described and characterized in 1997 (Asahara). We now know 
that these EPCS contribute to vessel and organ repair after ischemia to 
the heart, limbs and brain (Rafii, 2003). This is critically important 
as cardiovascular disease and stroke are two of the three biggest 
killers in the U.S. We have learned that by giving animials extra doses 
of these EPCS, we can improve their outcome from heart attack and 
salvage their limbs that are starved for blood.. Also, these EPCs can 
be mobllized from the bone marrow and into the peripheral blood with 
drugs and different growth factors . Some of these growths such G-CSF 
are already approved by the FDA for other indications
    The field is moving fast. Bone marrow-derived stem cells are 
already being tested in small numbers of patients with heart attacks. 
In the TOPCARE trial, bone marrow cells harvested from the same 
patient's bone marrow or their blood were delivered via a catheter in 
the coronary artery to injured heart tissue (Assmus, 2002). The 
procedure was safe and initial results were encouraging. There is also 
a trial using bone marrow cells in patients with congestive heart 
failure (Perin, 2003).
    Another type of bone marrow or blood stem cell is the human 
umbilical cord stem cell. These are derived from umbilical cords that 
are normally discarded after a delivery. Umbilical cord blood is a rich 
source of stem cells. These have already been exploited as a source of 
bone marrow transplants in the cancer field. These umbilical cord stem 
cells also have great potential as a treatment for neurological 
diseases. When delivered intravenously to a rodent with a stroke, they 
help improve the recovery from the stroke (Chen, 2001).
    Despite these hopeful signs, much work needs to be done. Before we 
are able to treat humans safely and effectively, we need to define the 
optimal dosing of these cells, the optimal type of bone marrow 
populations to use, the timing of when to administer, and the best 
route of administration (inject directly into the organ, intravenously, 
intra-arterially). We also need to learn more about how they these bone 
marrow cells and other adult stem cells home to damaged tissue so we 
can exploit this therapeutically.
    The major advantages of bone marrow derived stem cells are: 1) they 
are autologous (except for umbilical cord stem cells) and will not be 
rejected; 2) they can be easily isolated from bone marrow aspirates; 
and 3) they avoid the ethical concerns that many have with embryonic 
stem cells. However, we also have to keep in mind that repairing the 
nervous system is a daunting task. Neurons make tens of thousands of 
connections with other neurons. Some send their projections (axons) for 
meters and then connect to another cell. In most of the experiments so 
far we have little evidence that stem cells delivered into an adult 
will be able to make all these connections and become fully functional. 
It is likely that most of the cell transplants in the brain work by 
stimulating the brain to repair itself. We need to learn more about 
enhancing these endogenous (self) repair processes. In this growing 
field of ``Cell Therapy'', we will need to target diseases with 
specific cell types and approaches-one size will not fit all. We may 
need to treat some of these diseases with a combination of both 
``cells'' and growth factors. The treatments we develop for Parkinson's 
disease will be different from those we develop for stroke. There are 
no magic bullets-only painstaking research will allow us to advance.

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31

    Senator Brownback. What you're describing is exciting and I 
hope this is a field that we can put much additional research 
funding into.
    Dr. Rubinstein, thank you very much for joining us today.

  STATEMENT OF PABLO RUBINSTEIN, M.D., DIRECTOR OF PLACENTAL 
              BLOOD PROGRAM, NEW YORK BLOOD CENTER

    Dr. Rubinstein. Thank you very much, Senator. We are 
grateful for the opportunity to address this Committee.
    The work I will describe refers to the stem cells that are 
present in cord blood. This work, which will be presented by 
both myself and Dr. Kurtzberg, has taken place over a number of 
years, as I will describe.
    The first evidence that there were stem cells in cord blood 
was reported in 1974. From that time to the present, the most 
important elements in this history are the first cord-blood 
transplant that occurred in 1988. During the intervening years, 
there was a lot of research done that allowed this to happen. 
From 1988, where the first patient was transplanted by--a 
patient from Duke University, a patient of Dr. Kurtzberg's.
    The next big element was the setting up of a cord-blood 
program for treating patients without sibling donors, where we 
collect cord blood from unrelated donors, with informed 
consent, and this blood is frozen and then is available for use 
on anyone who needs them. The first unrelated cord-blood 
transplant from our repository at New York Blood Center was 
performed by Dr. Kurtzberg at Duke in 1993.
    And the next step in this story is the exemption granted by 
the FDA for us to continue this research and to expand the 
range of documented indices of the activities of these 
transplants. This year, there have been more than 3,500 
transplants performed worldwide, so far, with cord blood. Of 
these, more than 2,000 have been in the United States, and 
1,370 from our own cord-blood bank.
    The NIH has recognized the importance of this work and has 
created a second study, the COBLT study, which Dr. Kurtzberg 
participated, both of the transplanted and as a banker, to 
produce more of these transplants for patients in need. Dr. 
Kurtzberg will also report beautiful results that have been 
obtained with patients with cord-blood transplants that 
repaired, or at least helped to repair, tissues other than the 
blood and the immune system, which are a direct province of the 
stem cells in the cord blood.
    How is cord blood prepared and used? After the birth of a 
healthy baby, the placenta is removed, with the major segment 
of the cord, and the baby goes one way; the placenta is taken 
out. Normally, this placenta, with the segment of the cord, is 
discarded. In our case, we drain the blood that is left in the 
placenta, and we take it to the laboratory, process it, freeze 
it down, and, as the slide shows, we have special containers 
that allow us to freeze it in liquid nitrogen. At the 
temperature of liquid nitrogen, this blood will be available 
for transplantation for many years, without attrition. The 
blood is stored in special containers, which maintain control 
and information, directly in the same device.
    Results that have been obtained in the clinical use of this 
cord blood over the years allow us to compile a list of 
advantages that cord blood offers to clinicians and patients, 
in comparison with bone marrow. There are, first of all, no 
risks to the donors. There is no donor attrition. The blood 
will stay frozen until it's used. If it is processed correctly, 
it will be available for many years. We don't know how many, 
because it's longer than has been used, so far over 15 years. 
Grafts are available on short notice. They can be produced, and 
routinely are produced, in our case, within days, not months or 
years. There are fewer latent viral infections in cord blood 
than in adult bone marrow.
    But the main reason why this blood is so important is 
because the immune reaction that the donor's cells exert 
against the recipient's tissues, which is a problem with bone-
marrow transplantation, is much weaker in the case of cord 
blood; probably reflecting the biological status of that blood 
that comes from an organism in which the mother and the child 
have to tolerate each other. This advantage allows us to 
perform transplants with some mismatches. In bone-marrow 
transplantation, the more mismatches, the more problems occur 
for the patient; not just immediate, but for a long time for 
those patients who are successfully treated.
    That allows us, therefore, to find matches for people who 
have very much difficulty finding matches, people with rare 
types and people of ethnic minorities in which the 
opportunities to find a donor among those in the volunteer 
donor groups is much less, simply because there are fewer of 
them in the population.
    Another important result, which is now being shown in the 
slide, has been obtained in cooperation with the International 
Bone Marrow Transplant Registry. Several hundred patients 
transplanted with bone marrow were compared with cord-blood 
recipients for the same disease and the same age groups. The 
cord blood with no more than one mismatch, and the bone marrow 
with no more than one mismatch, as you can see offer exactly 
the same long-term transplant survival. What you're not seeing 
here is that the clinical condition of the patients is 
different. The cord-blood recipients usually have a much easier 
time, with much fewer chronic graft versus host disease than 
the bone marrow.
    Another thing the slide doesn't show is that the average 
result for all types of transplants that are taking place. And 
in the case cord blood, there is an additional influence. In 
addition to the matching is the cell dose. You can see, in the 
panel on the left, that people transplanted with small cell 
doses have a lower probability of long-term survival. But if we 
can eliminate, from our transplantation, the need to use those 
small cord bloods, we can shift the whole curve up and offer an 
overall larger probability of success.
    To terminate, I would just like to show you two slides, 
which refer to the need. It has been reported by the GAO, in 
October last year, the situation with bone-marrow 
transplantation that reflects the fact that in this country, at 
the moment, for people who need unrelated transplants, the 
opportunity to get the transplant is estimated at about 9 
percent of the total. For the period 1997 to 2000, of an 
estimated 44,000 patients who needed transplant, 4,056 got 
them--10 percent of the need, and about a quarter of all of 
those patients that went all the way to search officially.
    Finally, the other aspect of cord blood is, because of its 
tolerance of mismatches, it's possible to transplant patients 
of the different minority populations in our country with 
appropriate transplants. And, in this slide, you can see four 
populations--Asians, African Americans, Hispanic, and 
Caucasians. The African American is highlighted as an example. 
You will see, in the first part of the slide, that the 
proportion of African Americans, among all those who search, is 
about 12 percent, which reflects very closely with the size of 
the African American community in the national scope. However, 
the donors that were transplanted with bone-marrow transplants 
by the NMDP is only 6 percent, so only half as much chance as 
is available if they were equally--if they have equal access to 
the transplants. With cord blood, however, the probability is 
19 percent. And the reason for that is twofold. One is that we 
can make transplants that are less well matched. And, second, 
that we can select our donors by harvesting the cord blood in 
places where we can collect effectively, cord blood from 
members of these ethnic, and all the ethnic, groups. And, as a 
result, we can improve the access of these patients to 
transplantation.
    This is my part of the presentation. And now Dr. Kurtzberg 
will continue.
    Senator Brownback. Thank you very much, Dr. Rubinstein.
    And, Dr. Kurtzberg, I look forward to your testimony here 
today.

         STATEMENT OF JOANNE KURTZBERG, M.D., DIRECTOR,

            PEDIATRIC STEM CELL TRANSPLANT PROGRAM,

                 DUKE UNIVERSITY MEDICAL CENTER

    Dr. Kurtzberg. We're going to have a little technical 
switch here.
    Senator Brownback. All right.
    Dr. Kurtzberg. OK.
    Well, thank you very much for listening to our story today 
about cord blood. I'm going to continue by talking about the 
clinical applications of cord-blood transplantation, today and 
in the future.
    We've been very excited about cord-blood transplantation, 
because, as a transplant physician, I, and all others, are 
faced with patients who need the therapy and don't have donors. 
And cord blood has filled the niche for those patients, because 
it can be used without complete matching.
    Now, the child shown in this slide was the first recipient 
ever of a cord-blood transplant. He's from Salisbury, North 
Carolina, and was transplanted in 1988 with cord blood from his 
baby sister. And his transplant was extremely important, 
because there was no way to really demonstrate or prove, in 
animal model or in a test tube, that cord blood contains 
sufficient numbers of stem cells to reconstitute a patient. And 
there were many skeptics, and most people believed it wouldn't 
work. But this family was very courageous and allows his baby 
sister's cord blood to be used for his transplant for a rare 
genetic diseased, called Fanconi anemia. And he's shown----
    Senator Brownback. What was the disease?
    Dr. Kurtzberg. Fanconi anemia, which is an inherited 
disease that causes death in the first decade of life. It's a 
defect in DNA repair. And it affects all cells in the body; but 
first, the blood. And it leads to bone-marrow failure, or 
leukemia, causing death in the first decade of life.
    Senator Brownback. Thank you.
    Dr. Kurtzberg. This boy was successfully transplanted, 
successfully engrafted, is shown 15 years later, in the right-
hand panel, and is doing well; well, has a durable graft. 
Again, one of the questions a transplanter would have is, 
``Will the cells not only grow back at the beginning, but will 
they stay there, and will they remain and grow with the patient 
who received them?'' And he is the longest living survivor of a 
cord-blood transplant, the first recipient of a cord-blood 
transplant. And, at least at 15 years, we can say that this is 
a durable graft, without causing any late problems.
    Now, after his transplant, there were other related 
transplants performed in small numbers over the next 5 years, 
but the real breakthrough in cord-blood transplantation came 
when Dr. Rubinstein's bank was established and there was a pool 
of donors in the unrelated setting. And it's now been shown 
that cord blood can be used for all the applications of bone 
marrow and that includes those listed in the slide--hematologic 
malignancies, immune deficiencies, like the ``bubble boy'' 
disease, marrow-failure syndromes, hemoglobinopathies. And 
you'll hear from a sickle-cell anemia patient later, who has 
had his disease corrected with a cord-blood transplant.
    And then a very interesting category of diseases called the 
``inborn errors of metabolism,'' where babies are born missing 
enzymes that are necessary for development of the brain or the 
muscles or the heart or the skeletal system; and where, without 
therapy, they generally die in infancy or early childhood.
    Now, I only have time to show you a little bit of data from 
patients transplanted with cord blood; and I chose the genetic 
diseases to focus on, because I think they really illustrate 
lessons that we can learn to move into the field of 
regenerative medicine.
    This slide shows our results transplanting children with 
genetic immunodeficiency syndromes--where their immune system 
is absent at birth. And there are multiple forms of this 
disease. It's fatal in childhood, without treatment, either 
because of infection or cancer. And transplant is the only 
therapy that's curative.
    This little boy was transplanted at 18 months of age, when 
he was critically ill with a fungal infection, and really no 
one thought he would even make it through the transplant. And 
he's shown 3 years after transplant, successfully corrected 
with a normal immune system.
    Overall, in about 30 patients with this disease, we have an 
80 percent event-free survival, which is shown in that curve. 
And what that means is these children are alive, well, 
engrafted, and they have a recovered immune system that 
functions normally.
    Senator Brownback. And the children would have all died.
    Dr. Kurtzberg. They would have all died, yes. These are 
lethal genetic conditions.
    Another example is an inborn error called Hurler syndrome, 
where children are born missing an enzyme that's necessary for 
development of the brain, the liver, the bones, the cornea, and 
the cartilage. And this little girl is an example of a child 
transplanted with Hurler in infancy. These children generally 
die by the age of five to 10 years. And although they have 
severe mental retardation, they actually die of atherosclerotic 
heart disease because of deposits that fill up the coronary 
arteries and cause damage to the heart muscle. And transplant, 
again, will correct this disease. And, in our hands, 
transplanting now over 25 children, the event-free survival is 
90 percent. That means these children are engrafted, corrected. 
And I just showed you one example of a child transplanted at 5 
months of age, now 6 years old, with a normal IQ--actually, a 
high IQ--and she's a reflection, not an exception. All the 
children we've treated have had normal development and regained 
skills that they had lost.
    Senator Brownback. And normal IQ development.
    Dr. Kurtzberg. Yes, they are in the normal range.
    We also know that their bones have corrected, and that they 
have not developed coronary artery disease, which probably has 
implications for adult coronary artery disease, although the 
pathogenesis is different.
    A third disease that really falls into a category called 
leukodystrophy, where there's, again, children born with 
defects in myelination. Myelin is the covering of the nerve 
sheath in the white matter of the brain. And without that 
covering, the brain neurons are damaged and die. Krabbe disease 
is the most severe leukodystrophy, with the earliest onset, and 
children who have this disease generally develop normally for 
the first few months of life and then regress and are 
vegetative by a year of age, and die between one and two years 
of age.
    Now, the little boy in the picture lost a sibling to Krabbe 
disease, and the sibling died at 13 months of age. He's shown 
at 2 years of age, but he was transplanted at 3 weeks of age, 
because we knew, the cause of his sibling's death we know to 
look for the disease. And when he was diagnosed, we were able 
to mobilize a cord blood within a few days. We tested that cord 
blood to make sure that cord blood didn't carry the disease, 
and then go forward with a transplant in the first month of 
life. There have now been ten children treated in the United 
States with that same approach, and all ten are doing very well 
anywhere from one to 6 years later.
    The survival curves that are portrayed on the graph show 
you that the newborn transplants, which is the top of the line 
and is straight, at 100 percent, all are surviving, doing well, 
and developing normally. Children in the middle line, that goes 
down and evens out at about 40 percent, are children who had no 
family history. There was no way to know to look for the 
disease. They were diagnosed after they had symptoms, and they 
had some brain damage at that point. And those children have a 
40 percent event-free survival, and they are left with some 
disability, sometimes severe and sometimes mild.
    Senator Brownback. So the age that you catch this is very 
significant.
    Dr. Kurtzberg. Well, it's either the age or the amount of 
damage or both, and it's hard to know.
    And then the other line, that goes all the way down to 
zero, shows you the natural history of the disease in untreated 
children. In this case, there are 156 in the curve. And these 
are children whose families contacted us, and we evaluated, but 
we felt were too advanced with the disease for the procedure, 
and so they were not treated, and the disease ran its natural 
course.
    Now, this is an MRI picture. Now, I know it's a little 
complicated, but it shows the brain of a different child, who 
was also transplanted, with Krabbe, in the first 3 weeks of 
life. And what's interesting here is, this is her scan--moving 
into it with my arrow--at 1 year of age, the smaller brain; and 
then, on the left-hand panel, 2 years of age. And at 1 year of 
age, she has some fluffy stuff around the ventricles, which is 
inflammation, which is abnormal. But, at 2 years of age, that 
has regressed and has gone away. And, in addition, these gray 
lines show myelination, which is normal for age. Now, this 
child would not have been able to myelinate her brain if she 
had not been transplanted. And, in fact, she probably would not 
have survived to this age. But this shows actual repair on a 
scan in a child who is doing well.
    This last slide of this Krabbe story shows brain tissue 
from a child who died. The child was a girl, and she received a 
transplant from a boy. And these are nuclei of brain cells in 
the white matter and in something called the choroid plexus, 
which are the cells lining the ventricles. All the cells that 
have blue or green dots are male cells, donor cells, that have 
traveled to this child's brain and distributed throughout the 
brain. In fact, we found that 30 to 40 percent of the cells in 
her brain came from the donor, and we're investigating what 
kinds of cells they are.
    But, again, as you think of repairing neurologic damage, 
this is a hint that maybe these cells have the capacity to do 
that, and they certainly need to be examined further.
    Finally, I want to just end with a few comments about 
sickle-cell anemia and hemoglobinopathies. Sickle-cell anemia, 
as you'll hear later, can be cured by hematopoietic stem cell 
transplantation, either from bone marrow or from cord blood. 
But many patients don't have donors. And we have transplanted a 
few patients with sickle-cell disease and leukemia, and cured 
both diseases.
    The little boy in the picture here is a surgeon's son, who 
has thalassemia, which is another kind of hemoglobinopathy, and 
he was the first recipient of a cord-blood transplant for 
hemoglobinopathy, at two-and-a-half months of age, before the 
disease had caused any damage to any of his organs. And he is 
going well, at 5 years of age, without any symptoms or problems 
from the disease.
    Personally, I believe that we should be taking the same 
approach for sickle cell, using the transplant very early in 
childhood or infancy, where the transplant survival rates are 
better. This graph shows you event-free survival after related 
cord-blood transplants, and they are 90 percent survival, and 
80 percent of event-free survival in thalassemia and sickle-
cell disease, respectively. And so this works and is better 
than much of the morbidity that much of the patients who suffer 
with this disease later will experience.
    Also, cord blood has a role here for African American 
patients, who otherwise can't find donors very quickly.
    Cord blood has a lot of applications right now, in the 
diseases I mentioned and others. It also has applications, I 
think, in the future for cellular therapies, along with other 
stem cell sources. And our real request here is to continue to 
be able to bank cord blood in the public setting.
    And very briefly, Dr. Rubinstein told you the history, but 
the NHLBI had funded both his first public cord-blood bank, and 
then a second group of banks, under a program called COBLT. 
Those banks and Dr. Rubinstein's bank have proven that this is 
an important resource. But now there's no continued funding to 
take this resource, where really about $20 million was already 
expended to build it up and continue it. It needs to transfer 
over to the service sector and be supported through federal 
dollars.
    So our proposal is to establish a national cord-blood 
program, which will provide grafts for patients in need now and 
provide an inventory of cells for research and future cellular 
therapies, and we need to have funding to create a network of 
four to six banks in the United States that will network 
together to build an inventory of about 100 to 150,000 units, 
which are the numbers needed to solve the problems that Dr. 
Rubinstein illustrated with cell dose and matching.
    I'll stop there. Thank you.
    [The prepared statement of Dr. Rubinstein and Dr. Kurtzberg 
follow:]

                               Cord Blood

   A Source of Stem and Progenitor Cells for Patients in Need ofBone 
          Marrow Transplantation and Other Cellular Therapies

  Pablo Rubinstein, M.D., New York Blood Center and Joanne Kurtzberg, 
                         M.D., Duke University

                      Cord Blood Research Progress




 1974:                First Report on Stem/Progenitor Cells in
                               Human Cord Blood

 1988:                First Cord Blood Transplant (Sibling)

 1992:                First Public Cord Blood Bank
                              (Unrelated Donors. NIH-sponsored Research)

 1993:                First Unrelated Cord Blood Transplant

 1996:                First FDA IND + NIH Sponsored COBL T Study

 2003:                More than 3500 Cord Blood Transplants
                               Worldwide, 2000 in U.S.

 2003:                Donor-type Cells of Non-Blood or Immune
                               Lineages and Evidence of Myelin
                               Regeneration in Patients with lysosomal
                               storage diseases after Cord Blood
                               Transplant


                               
                               
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    Senator Brownback. Is there legislation introduced to do 
that, on either the House or the Senate side? Do you know?
    Dr. Kurtzberg. There is one in progress, but it has not 
been introduced yet.
    Senator Brownback. OK.
    Dr. Kurtzberg. There's a draft of a bill.
    Senator Brownback. All right. Because we'll sure want to 
get that out and do that for you. This is very encouraging. And 
if you were one of the parents of one of those children, this 
is the hope you've been looking for.
    Dr. Kurtzberg. I've personally treated over 500 patients, 
and I have seen this work in children with otherwise fatal 
diagnoses. So it's very important to be able to continue the 
work.
    Senator Brownback. I'm sure that parents are absolutely 
ecstatic when they see that and see you. You're----
    Dr. Kurtzberg. Sometimes.
    Senator Brownback.--an angel to them.
    Dr. McDonald, thank you very much for joining us and for 
being here today.

           STATEMENT OF JOHN W. McDONALD, M.D., Ph.D.

         DEPARTMENT OF NEUROLOGY, WASHINGTON UNIVERSITY

                       SCHOOL OF MEDICINE

    Dr. McDonald. Good afternoon, Mr. Chairman.
    I'm Dr. John W. McDonald, and I'm an Assistant Professor at 
the Department of Neurology and Neurological Surgery and 
Director of the Spinal Cord Injury Program, at Washington 
University School of Medicine, in St. Louis. I'm also a staff 
physician at Barnes-Jewish Hospital, the Rehab Institute of St. 
Louis and St. Louis Children's Hospital.
    I'm here today on behalf of the Coalition for the 
Advancement of Medical Research, a coalition of over 75 
patient, scientific, and university organizations dedicated to 
ensuring that all forms of stem cell research be allowed to be 
explored here in the United States.
    The Coalition started 2 years ago to ensure that stem cell 
research receives the same sorts of funding that all other 
research receives from the Federal Government. The group also 
is dedicated to ensuring that critical cutting-edge research is 
not criminalized.
    As the Director of the Spinal Cord Injury Program, I see 
thousands of children and adults with devastating neurologic 
injuries, including spinal-cord injuries. These patients really 
have no practical alternatives for recovery of function after 
the injury has already occurred, such simple things as recovery 
of bowel and bladder control, or simply feeling a loved-one's 
embrace. And only some of the 11,000 people who are injured 
every year recover any substantial function with traditional 
rehabilitation, which assumes that recovery is only possible 
after 6 months to 2 years.
    I'm currently working on a variety of ways to treat 
patients with spinal-cord injury or disease. And shown now is 
an example of a T2 weighted MRI image, the spinal cord is in 
the middle, if you see, down to the red box, it actually shows 
where the injury is. A really minute injury at this point in 
the nervous system becomes a really devastating problem. And I 
mentioned that there's 11,000 people injured each year. There's 
a quarter of a million living with spinal-cord injury, and 
another four to five times that many with medical causes of 
spinal-cord injury, such as multiple sclerosis or ALS.
    I've been working on a variety of ways to treat patients 
with spinal-cord injury and disease. For example, I've seen 
significant improvements in a very small group of patients, 
using activity-based therapy. This is a therapy that relies on 
providing pattern activations for someone who's completely 
paralyzed, like putting a paralyzed person on a functional 
electrical stimulation bike, with this idea that the nervous 
system requires optimal activity in order for new cells to be 
born to optimize regeneration, now that we understand that the 
adult nervous system does have some limited capacity for 
regeneration.
    Shown here on this graph is the results of a patient that 
participated in this. Now, let me preface this by saying that 
this individual was completely paralyzed, from the neck down, 
from just below C-2 down, unable to breathe, move, or feel 
below that level, for the first 5 years. Traditional history 
would say that there's no opportunity, absolutely, that this 
individual could regain any substantial function. And this 
individual began to recover substantial motor function, being 
able to move most of the joints in his body, to about 20 
percent of normal on the scale. Of more importance was the 
recovery of sensation, which was about 70 percent of normal. 
Again, over the first 5 years, there was very limited recovery, 
and then a progressive recovery over the last 3 years, after 
institution of the activity-based recovery program, in the 
middle of 1999.
    We've done additional research now in animals that 
demonstrates that this type of activity actually mobilizes the 
stem cells that are present in the spinal cord below the level 
of the injury. What happens, below the level of the injury, in 
a chronic situation, is that the number of stem cells are 
reduced, unable to be there to be able to replace cells that 
are lost. And this activity appears to be repleting those cells 
so that they're available, inasmuch as a stem cell transplant 
would allow.
    Senator Brownback. By the physical stimulation that's 
taking place.
    Dr. McDonald. Right.
    Now, while adult stem cells have potential for 
significantly improving clinical treatment of a wide range of 
diseases, I believe it's critical that we also explore the use 
of embryonic stem cells.
    If you compare stem cells to a tree, adults stem cells have 
already developed and specialized down a particular path, or 
limb. On the other hand, embryonic stem cells are still at the 
base of the trunk, ready to be guided down any number of limbs. 
It's, therefore, much more feasible to try to encourage 
embryonic stem cells to develop into whatever cell type is 
needed.
    As you can see from this video, this is an animal that's 
treated, 9 days after a spinal-cord injury, with embryonic stem 
cells that have been induced to become neuro progenitors. This 
is an animal that's just a control; treated identically, except 
no cells. You can see it has great difficulty moving its hind 
limbs, raising his tail, and basically drags his behind.
    The next slide is a similar animal, but it's been 
transplanted with embryonic stem cells, and you can see, 
really, a marked improvement in its ability to walk, stand on 
its hind limbs, and lift his tail. And the stage at which these 
cells were transplanted were neuro progenitors similar to those 
that can be derived from ESLs.
    So, as you can see from the video, we have already found 
encouraging support for the use of embryonic stem cells to cure 
or treat some of the most debilitating diseases. The two rats 
that you have just seen have the same injury, but the rat that 
received the transplanted embryonic stem cells has recovered 
significantly more use of its hind limbs and tail.
    My hope is that one day the patients that I see in the 
Spinal Cord Injury Program will also be able to regain 
movement, just like that rat in this video.
    And as a scientist, I cannot guarantee that embryonic stem 
cells will lead to cures and treatments. I can tell you, 
however, that they hold great promise. Science is a process in 
which we knock on 20 doors; 19 open, with nothing behind them; 
one opens to reveal a pot of gold. We can't predict which door 
will be the magic door.
    The field of stem cell research, whether it be embryonic, 
adult, cord-blood stem cells, is extremely new. It's entirely 
too early to rule out any one of these areas of research in 
favor of another. But my wheelchair-bound patients should not 
have to wait for us to explore each possibility one at a time.
    In the years that have been spent debating the issues here 
in Washington, research that could 1 day lead to cures and 
treatments for so many diseases has been held back. Some senior 
researchers have either left the United States to work 
elsewhere or have decided to work in other areas of biomedical 
research. And, more importantly, many of the next generation of 
researchers have decided to stay away from these areas because 
of the uncertain political environment.
    Mr. Chairman, please allow all forms of stem cell research 
to move forward--adult, cord blood, and embryonic--so that we 
can continue to look for medicine's pot of gold.
    Thank you.
    [The prepared statement of Dr. McDonald follows:]

   Prepared Statement of John McDonald, M.D., Ph.D. on behalf of the 
           Coalition for the Advancement of Medical Research

    Good afternoon Mr. Chairman and members of the Committee. I am Dr. 
John W. McDonald and I am an Assistant Professor in the Departments of 
Neurology, Neurological Surgery, Anatomy and Neurobiology and Director 
of the Spinal Cord Injury Program at Washington University School of 
Medicine in St. Louis. I am also a staff physician at Barnes-Jewish 
Hospital, the Rehabilitation Institute of St. Louis and St. Louis 
Children's Hospital.
    I am here today on behalf of the Coalition for the Advancement of 
Medical Research,* a coalition of over 75 patient, 
scientific and university organizations dedicated to ensuring that all 
forms of stem cell research be allowed to be explored here in the 
United States. The Coalition started two years ago to ensure that stem 
cell research receives the same sorts of funding that all other 
research receives from the Federal government. The group also is 
dedicated to ensuring that critical, cutting-edge research is not 
criminalized.
---------------------------------------------------------------------------
    \*\ The Coalition is comprised of nationally-recognized patient 
organizations, universities, scientific societies, foundations, and 
individuals with life-threatening illnesses and disorders, advocating 
for the advancement of breakthrough research and technologies in 
regenerative medicine--including stem cell research and somatic cell 
nuclear transfer--in order to cure disease and alleviate suffering.
---------------------------------------------------------------------------
    As the director of the Spinal Cord Injury Program, I see thousands 
of children and adults with devastating spinal cord injuries. These 
patients have no real hope for recovering functions most of us take for 
granted, from bowel and bladder control to simply feeling a loved one's 
embrace. And only some of the 11,000 people who get injured each year 
recover with traditional rehabilitation, which assumes that recovery is 
only possible after six months to 2 years.
    I am currently working on a variety of ways to treat patients with 
spinal cord injury or disease. For example, I've seen significant 
improvements in a very small group of patients using activity-based 
therapy, which relies on electrical stimulation to help patients 
exercise their paralyzed limbs. While significant, even those successes 
are minimal and extremely preliminary--it's still unclear whether these 
techniques can help most spinal cord injuries, and to what extent they 
alone can restore function. We need to examine other promising 
approaches, and I believe that embryonic stem cells have the most 
potential.
    While adult stem cells also have potential for significantly 
improving clinical treatment of a wide range of diseases, I believe it 
is critical that we also explore the use of embryonic stem cells. If 
you compare stem cells to a tree, adult stem cells have already 
developed and specialized down a particular path, or limb. On the other 
hand, embryonic stem cells are still at the base of the trunk, ready to 
be guided down any of a number of limbs. It's therefore much more 
feasible to try to encourage embryonic stem cells to develop into 
whichever type of cell is needed.
    As you can see from the video, we have already found encouraging 
support for the use of embryonic stem cells to cure or treat some of 
the most debilitating diseases. The two rats you see have the same 
injury, but the rat that received transplanted embryonic stem cells has 
recovered significantly more use of its hind legs and tail.
    My hope is that one day the patients I see in the Spinal Cord 
Injury Program will also be able to regain movement, just like the rat 
in this video.
    As a scientist, I cannot guarantee that embryonic stem cells will 
lead to cures and treatments. I can tell you, however, that they hold 
great promise. Science is a process in which we knock on 20 doors: 
Nineteen open with nothing behind them; One opens to reveal a pot of 
gold. We cannot predict which door will be that magic door. The field 
of stem cell research, whether it be embryonic, adult or cord blood 
stem cells, is still extremely new. It is entirely too early to rule 
out any one of these areas of research in favor of any other. My 
wheelchair bound patients should not have to wait for us to explore 
each possibility one at a time.
    In the years that have been spent debating the issue here in 
Washington, research that could one day lead to cures and treatments 
for so many diseases has been held back. Some senior researchers have 
either left the United States to work elsewhere or have decided to work 
in other areas of biomedical research. And many of the next generation 
of researchers has decided to stay away for these areas because of the 
uncertain political environment. Mr. Chairman, please allow all forms 
of stem cell research to move forward, adult, cord-blood and embryonic, 
so that we can continue to look for medicine's pot of gold.

    Senator Brownback. Thank you, Dr. McDonald. And thank you 
for your passion and your heart and your work to help others be 
able to walk.
    Dr. Peduzzi-Nelson, we have 12 minutes, I think, they're 
just telling me, left in the vote. So I think we'll try to get 
your testimony in before I head over to vote.
    But I'm delighted to have you here, and please proceed with 
your testimony.

           STATEMENT OF JEAN D. PEDUZZI-NELSON, Ph.D.

               DEPARTMENT OF PHYSIOLOGICAL OPTICS

              UNIVERSITY OF ALABAMA AT BIRMINGHAM

    Dr. Peduzzi-Nelson. What I'm going to show is that these 20 
doors are partially opened. We can see what doors contain the 
pots of gold and what doors contains gremlins that we need to 
close permanently. I agree with Dr. McDonald that we're not 
knocking on these doors equally. Even with the Federal ban, the 
vast majority of studies are still using embryonic animal stem 
cells and human stem cell lines. The ban does not affect animal 
stem cell research. Using a person's own stem cells is the area 
of research that's being neglected.
    I would like to quickly review the results of some clinical 
and pre-clinical trials that clearly shows where the pots of 
gold are and where the gremlins are. We've already heard some 
testimony that there's definitely pots of gold for a number of 
children, using human umbilical cord blood, and also that the 
work that Dr. Hess presented, using bone marrow, and also Dr. 
McDonald's work with rehabilitative therapy--are all very 
viable, wonderful areas to pursue.
    In terms of spinal-cord injury, I'd like to present the 
results of two clinical trials and show their results using an 
exact same test. In these trials, they were using tissue, 
neural tissue. And how this relates to the stem cell issue is, 
if you put this tissue--transplant it into the brain or spinal 
cord, the cells that survive are the stem cells, or the early 
derivatives of these stem cells.
    In a clinical trial that took place at the University of 
Florida that began in 1997, minced fetal spinal-cord tissue was 
used. The results of the first two patients have been published 
and are presented on the left side of the first three graphs. 
Their finding was that there was very little change in their 
condition. However, in another study that's an ongoing trial in 
Portugal, person's own olfactory mucosa was used. All of the 
patients in this study, as you can see in the first graph, in 
the light-touch ASIA scores, and in the next graph, using the 
pin-prick ASIA scores, and in the next graph, using the motor 
scores, that there was some improvement in actually all the 
patients that received the transplant by the first month after 
the transplant of their own olfactory mucosa.
    And furthermore, the first patient that was treated, after 
15 months after--16 months after the treatment, regained 
bladder control. And I don't if many people in the audience 
know this, but this is a very severe problem with people with 
spinal-cord injury. And this woman no longer needs catheters at 
all.
    What's interesting is, at the Portuguese studies, they had 
no rehabilitative methods available to them. There was no rehab 
therapy at all. The improvement was all what just happened 
naturally. And much greater improvement might have occurred if 
they had resources to have rehab therapy.
    I'd like to move on to--in the next graph, to the results 
of two Parkinson's trials. These are clinical trials that 
clearly show some difference in the results. In a study by 
Freed and Associates done several years ago, human fetal stem 
cells were injected into the brain. And, on the left, you see 
the results of that study. There was a 28 percent improvement 
in the younger patients. ``Younger,'' in this study, which I 
like, means less than 60 years old. However, at about 1 year 
after the transplant, there was a very devastating result in 15 
percent of the patients. They got significantly worse because 
of overgrowth of these embryonic cells that were placed in the 
brain, and they were much worse in function than they had been 
previously.
    However, there's been another clinical trial in 
Parkinson's, and this was using the person's own stem cells 
from their brain. And this was a study done by Dr. Michel 
Levesque, in California. In this case, in this patient, there 
was an 83 percent improvement, and the patient had the 
treatment 2 years, and no detrimental side effects have been 
observed.
    The experimental studies, animal studies, also provide 
indication of what is behind the doors. First, in the next 
slide, it's true, maybe you can't make a whole tree from adult 
neural stem cells, the cells that are from the brain. However, 
there's lots of other stem cells in the body. So why would you 
even try to make every stem cell from an adult neural stem 
cell?
    Also, we know that you can make neurons, muscle cells, 
blood cells, from the stem cells in the adult brain. Also, you 
can get neurons or nerve cells or support cells to develop from 
bone, as Dr. Hess has mentioned, from skin, from blood, and my 
favorite, from fat stem cells.
    Second, the experimental studies that have been done using 
embryonic stem cells, as do the clinical trials, show that 
embryonic stem cells are dangerous, especially in terms of 
overgrowth. And studies by Bjourland and also by Dr. Gage and 
others have found tumor formation and sometimes blockage of the 
ventricular system can occur using embryonic stem cells.
    Third, my own work in rats with chronic severe spinal-cord 
injury show that adult stem cells can lead to a functional 
improvement.
    I think that it really gets down to a very basic question. 
If you or your loved one had a serious disease or injury, would 
you like them, or yourself, to receive your own stem cells or 
fetal, embryonic, or cloned stem cells? I think you don't have 
to be a scientist to answer that question. But the answer to 
the question is also supported by the clinical trials and the 
pre-clinical animal trials that have been done so far.
    I would like to end by saying that the reason I'm here is 
that the victims of terrible diseases and injuries are again 
becoming victims to support a therapy that's not in their best 
interest. With only a limited amount of funding available, more 
focus is needed in directing research in areas that can help 
people in the next five to 10 years, not several lifetimes 
away.
    Thank you.
    [The prepared statement of Dr. Peduzzi-Nelson follows:]

  Prepared Statement of Jean D. Peduzzi-Nelson, Ph.D., Department of 
       Physiological Optics, University of Alabama at Birmingham

                         ``The Y in the Road''

    Thank you Senator Brownback and Senator McCain and distinguished 
senators of the subcommittee for the invitation to present to you 
today. Stem cells are a major medical breakthrough with tremendous 
potential but we are now at a ``Y in the road'' as far as the future of 
medicine. In deciding our course, the way is clouded by opposing 
ethical views, vested interests of certain scientists & the biotech 
community, political allegiances and celebrities. I would like the 
members of the subcommittee and the audience to set aside all those 
factors for just a few minutes. I ask you now to think about a very 
basic question: If your loved one was suffering from a terrible injury 
or disease, what type of stem cell treatment do you think would work 
the best: (1) their own cells or (2) cells derived from embryos, 
fetuses or cloned embryonic cells? I don't think you need to be a 
scientist to answer that question. It also turns out that if you look 
at the scientific evidence, not speculation about the future by 
prominent scientists on either side of the issues, but just the facts 
of where we are today based on clinical and preclinical trials, the 
logical choice in medical treatment is also the best medical treatment.



    I would now like to review the scientific data that prove that an 
intuitively obvious concept is also supported by the results of recent 
clinical trials and preclinical trials (experimental animal studies). 
First, I would like to review the clinical trials using stem cells and 
their derivatives in spinal cord injury and Parkinson's disease. Two 
clinical trials using fetal tissue have been done in the U.S. and one 
on-going clinical trial in Portugal using a person's own tissue. All of 
these spinal cord injury trials are important to the question of stem 
cell research because the cells that survive after the tissue 
transplant are the stem cells and their early derivatives. The mature 
cells in the tissue except for some support cells would die off. The 
first study using fetal tissue was done at the University of Florida, 
beginning in 1997, in the treatment of syringomelia--a condition in 
which a large cavity forms in the spinal cord. Minced spinal cords (SC) 
from 4-8 different human fetuses taken from elective abortions were 
grafted into the cavity in the spinal cord. At 18-month follow-up of 
the first 2 patients, the condition of the patients was not very 
different.\1\ Another study was performed more recently using pig fetal 
tissue at Washington University and SUNY/Albany. There have been no 
further announcements regarding this study although the first patient 
was done in April 2001.\2\ The study in Portugal has had impressive 
results using a person's own olfactory mucosa.\3\ The olfactory mucosa 
lines the upper nasal cavity and contains stem cells and cells that 
encourage growth of nerve cell processes called olfactory ensheathing 
cells. Patients with severe (complete) spinal cord injuries were 
operated at 6 months following the injury. Other patients in this study 
(not reported below) were up to 7 years post-injury with similar or 
better results. On the next page are the charts comparing the results 
from the first 2 patients from each of the 2 different trials. In 
comparing the results of using embryonic tissues or using one's own 
tissue:
---------------------------------------------------------------------------
    \1\ Wirth E.D. 3rd, Reier P.J., Fessler R.G., Thompson F.J., Uthman 
B., Behrman A., Beard J., Vierck C,J., Anderson D.K. Feasibility and 
safety of neural tissue transplantation in patients with 
syringomyelia.Journal of Neurotrauma. 18(9):911-29, 2001.
    \2\ http://www.diacrin.com/SCI%20Albany%20Surg.htm
    \3\ Parks, D. Birmingham, News, Sunday, December 8, 2002, Olfactory 
nerves could help mend spinal injuries. http://www.scsnw.com/
Nerves%20in%20nose%20may%20repair%20spinal%20
cord%20injuries.htm

  (1)  There was little change in the condition of the patients using 
        the embryonic tissue. There appeared to be no massive rejection 
        even though 4-8 different embryos were used for each patient in 
        the University of Florida trial and no reports of rejection in 
        the trial using pig cells used in Washington University and 
---------------------------------------------------------------------------
        SUNY/Albany.

  (2)  In the Portuguese study, there were increases in motor and/or 
        sensory scores by 1 month in almost all the patients receiving 
        their own olfactory mucosa suggesting that a person's own 
        tissue is more effective. The first patient done regained 
        bladder control at 16 months after the treatment and no longer 
        uses catheters. The second patient that had less improvement 
        was the patient that had the largest lesion (6 cm) of all of 
        the patients done so far.

    The changes observed might have been greater for the patients 
treated in Portugal if rehabilitative therapy was available there.







    The clinical trials in Parkinson's disease had dramatic differences 
in their findings depending on the original source of the cells: 
fetuses or the person's own cells. In both cases, the cells were 
matured in culture before being transplanted into the patient. A 
clinical trial was done by Dr. Freed and colleagues in which 19 
patients received cells derived from 4 different fetuses with abortions 
at 7-8 weeks after conception.\4\ The patients that were under 60 years 
showed about a 28 percent improvement in the Unified Parkinson's 
Disease Rating Scale (UPDRS). About 15 percent of these patients showed 
severe decline in function at 1 year after treatment. In another 
Parkinson's study done by Dr. Michel Levesque, the patient who was 57 
years old at the time of treatment, received cells derived from his own 
brain stem cells.\5\ This patient showed an 83 percent improvement in 
the UPDRS. Below is a chart that summarizes the percentage improvement 
in the 2 clinical trials.
---------------------------------------------------------------------------
    \4\ Freed C.R., Greene P.E., Breeze R.E., Tsai W.Y., DuMouchel W., 
Kao R., Dillon S., Winfield H., Culver S., Trojanowski J.Q., Eidelberg 
D., Fahn S. (2001) Transplantation of embryonic dopamine neurons for 
severe Parkinson's disease. New Engl. J. Med.. 344:710-9.
    \5\ Levesque, M.F. and T. Neuman Autologous transplantation of 
adult human neural stem cells and differentiated dopaminergic neurons 
for Parkinson's disease: one year post-operative clinical and 
functional metabolic results. AANS31, 2002.



    The greater improvement and lack of harmful late effects using a 
person's own cells is primarily due to the fact that the cells were 
derived from an adult as opposed to fetuses. Of lesser contribution to 
the overall improvement probably was that the cells were genetically 
identical and not rejected. There was no evidence of massive rejection 
in any of the studies using fetal cells/tissues, even when pig cells 
were used without long-term immune-suppressing drugs to prevent 
rejection. However, better results were obtained using person's own 
adult cells. The study by Freed and colleagues also suggests that the 
primary problem with the fetal cells is not rejection. Using cells 
derived from fetuses, the severe functional deterioration seen in 
several patients was due to overgrowth of the cells derived from 
fetuses, not a lack of cell survival.
    It is rather ironical that the qualities cited for the superiority 
of embryonic or fetal stem cells are actually responsible for causing 
problems. Rapid growth is not always a desirable quality as clearly 
seen with weeds in a garden or cancer in the body. In the Parkinson's 
study, cells derived from the embryo and the adult were both allowed to 
mature in culture, but the end result was quite different. As the graph 
demonstrates, the patient's own cells markedly improved and no 
debilitating side effects were observed. A possible explanation for 
these findings is that adult stem cells are the natural components of 
the adult body and endogenous mechanisms exist to control their growth 
and maturation to replace damaged neurons.\6\ The cells from the adult 
may have certain molecules on their surface (ligands or receptors) that 
keeps the cells from uncontrolled growth. Both studies allowed the stem 
cell to mature before implantation. If maturation of stem cell is a 
necessary safety step, then the fact that embryonic cells are so 
immature is a disadvantage. It would be possible and simpler to have 
large-scale commercialization of cells derived from embryos or fetuses 
but the end product would be grossly inferior for the recipients. There 
are many types of adult human stem cells that are readily available 
that lack the problems of overgrowth, rejection, and disease 
transmission. Most people do not need a total body replacement. Even if 
costly and complicated procedures of cloning are done to produce the 
human stem cells (not technically possible yet), the cells will not be 
genetically identical because of the mitochondrial DNA and improper 
imprinting. There is evidence that the debate is raging in the 
scientific community. A recent scientific article describing a clinical 
trial included an opinion that the authors, although using a patient's 
own blood stem cells, in no way support a ban on using human embryonic 
stem cells.\7\
---------------------------------------------------------------------------
    \6\ van Praag H. Schinder A.F. Christie B.R. Toni N. Palmer T.D. 
Gage F.H. Functional neurogenesis in the adult hippocampus. Nature. 
415(6875):1030-4, 2002.
    \7\ Janson C.G., T.M. Ramesh, M.J. During, P. Leone and J. Heywood 
2001 Human intrathecal transplantation of peripheral blood stem cells 
in amyotrophic lateral sclerosis. J Hematotherapy & Stem Cell Res 
10:93-915.
---------------------------------------------------------------------------
    Preclinical Trials: Preclinical trials (experimental animal 
studies) not only provide the basis for future clinical trials 
described above, but also support the same conclusion that is reached 
in reviewing the clinical trials. There is abundant evidence that adult 
stem cells can be used as a therapy and are readily available in 
people. The conclusion from the preclinical studies is that adult stem 
cells work just as well, if not better, than embryonic stem cells and 
are probably safer.\8\ There is no need for embryonic stem cells 
especially cloned ones.
---------------------------------------------------------------------------
    \8\ Bjorklund L.M.. Sanchez-Pernaute R.. Chung S.. Andersson T.. 
Chen I.Y.. McNaught K.S.. Brownell A.L.. Jenkins B.G.. Wahlestedt C.. 
Kim K.S.. Isacson O. Embryonic stem cells develop into functional 
dopaminergic neurons after transplantation in a Parkinson rat model. 
[comment]. [Journal Article] Proceedings of the National Academy of 
Sciences of the United States of America. 99(4):2344-9, 2002.
---------------------------------------------------------------------------
    Ten years ago, it was discovered that stem cells exist in the adult 
brain and spinal cord and can be readily isolated.\9\ \10\ Many initial 
ideas about adult stem cells in the brain were wrong. For example, the 
cells were first thought to only be present in rodents, but later found 
in people.\11\ It was once thought that only embryonic stem cells have 
the capacity to become many different cell types. More recently, it has 
been found that neural stem cells from adults have this potential.\12\ 
Stem cells and their cellular derivatives may be useful in many ways. 
In the nervous system, they can be replacement neurons, source of 
growth factors, or a substrate of growth. Another misconception was 
that adult stem cells might not be functional in their ability to 
transmit a signal to another neuron. There is recent evidence that 
adult stem cells can mature and form functional connections with other 
neurons in culture.\13\ \14\ A surprising finding was that many cells 
in the adult (not just the cells in the brain and spinal cord) have the 
potential to be neurons. Sources of adult human stem cells that are 
capable of forming neurons include the brain,\15\ \16\ olfactory mucosa 
in the upper nose,\17\ \18\ cornea,\19\ choroid and sclera \20\ of the 
eye, teeth,\21\ bone marrow.\22\ \23\ and skin.\24\ Further evidence 
that bone marrow can be a source of neurons for the brain is supported 
by findings in the patients' brains who have received bone marrow 
transplants.\25\ There is no reason to use embryonic/fetal tissue or to 
clone people to obtain genetically similar embryonic stem cells when 
there is a ready supply of stem cells in adult humans.
---------------------------------------------------------------------------
    \9\ Reynolds B.A., Wiess S. 1992. Generation of neurons and 
astrocytes from isolated cells of the adult mammalian central nervous 
system. Science 255:1701-1710.
    \10\ Richards, Lric T.J., Bartlett P.F. 1992. De nonv generation of 
neuronal cells from the adult mouse brain. Proc. Natl Acad Sci USA 
89:8591-8595.
    \11\ Eriksson P.S., Perfilieva E., Bjork-Eriksson, T., Alborn A.M., 
Nordborg C., Peterson D.A., Gage F.H. 1998. Neurogenesis in the adult 
human hippocampus. Nat Med. 4:13113-1317.
    \12\ Gritti A., Vescovi A.L., Galli R. Adult neural stem cells: 
plasticity and developmental potential. Journal of Physiology-Paris. 
96(1-2):81-90, 2002.
    \13\ Toda H., Takahashi J., Mizoguchi A., Koyano K., Hashimoto N., 
Neurons generated from adult rat hippocampal stem cells form functional 
glutamatergic and GABAergic synapses in vitro. Experimental Neurology. 
165(1):66-76, 2000.
    \14\ Song, H-j, C.F. Stevens, F.H. Gage, Neural stem cells from 
adult hippocampus develop essential properties of functional CNS 
neurons. Nature Neuroscience5: 438-445, 2002.
    \15\ Suslov O.N., Kukekov V.G., Ignatova T.N., Steindler D.A. 
Neural stem cell heterogeneity demonstrated by molecular phenotyping of 
clonal neurospheres. Proceedings of the National Academy of Sciences of 
the United States of America. 99(22):14506-11, 2002.
    \16\ Akiyama Y., Honmou O., Kato T., Uede T., Hashi K., Kocsis J.D. 
Transplantation of clonal neural precursor cells derived from adult 
human brain establishes functional peripheral myelin in the rat spinal 
cord. Experimental Neurology. 167(1):27-39, 2001.
    \17\ Murrell W., Bushell G.R., Livesey J., McGrath J., MacDonald 
K.P., Bates P.R., Mackay-Sim A. Neurogenesis in adult human. 
NeuroReport. 7(6):1189-94, 1996.
    \18\ Feron F.. Perry C., McGrath J.J., Mackay-Sim A. New techniques 
for biopsy and culture of human olfactory epithelial neurons. Archives 
of Otolaryngology--Head & Neck Surgery. 124(8):861-6, 1998.
    \19\ Seigel G.M., Sun W., Salvi R., Campbell L.M., Sullivan S., 
Reidy J.J. Human corneal stem cells display functional neuronal 
properties. Molecular Vision. 9:159-63, 2003.
    \20\ Arsenijevic Y., Taverney N., Kostic C., Tekaya M., Riva F., 
Zografos L., Schorderet D., Munier F. Non-neural regions of the adult 
human eye: a potential source of neurons?. Investigative Ophthalmology 
& Visual Science. 44(2):799-807, 2003.
    \21\ Miura M., Gronthos S., Zhao M., Lu B., Fisher L.W., Robey 
P.G., Shi S. SHED: Stem cells from human exfoliated deciduous teeth. 
Proceedings of the National Academy of Sciences of the United States of 
America. 100(10):5807-12, 2003.
    \22\ Deng W., Obrocka M., Fischer I., Prockop D.J. In vitro 
differentiation of human marrow stromal cells into early progenitors of 
neural cells by conditions that increase intracellular cyclic AMP. 
Biochemical & Biophysical Research Communications. 282(1):148-52, 2001.
    \23\ Hung S.C., Cheng H., Pan C.Y., Tsai M.J., Kao L.S., Ma H.L. In 
vitro differentiation of size-sieved stem cells into electrically 
active neural cells. Stem Cells. 20(6):522-9, 2002.
    \24\ Toma J.G., Akhavan M., Fernandes K.J., Barnabe-Heider F., 
Sadikot A., Kaplan D.R., Miller F.D. Isolation of multipotent adult 
stem cells from the dermis of mammalian skin. Nature Cell Biology. 
3(9):778-84, 2001.
    \25\ Mezey E., Key S., Vogelsang G., Szalayova I., Lange G.D., 
Crain B.Transplanted bone marrow generates new neurons in human brains. 
Proceedings of the National Academy of Sciences of the United States of 
America. 100(3):1364-9, 2003.
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    There are several studies that support the usefulness of adult stem 
cells. Stem cells obtained from adult spinal cord have been shown to 
survive and mature into neurons when transplanted into the brain.\26\ 
Transplantation of stem cells from adult human brain causes myelination 
to occur in a focally demyelinated spinal cord of the rat.\27\ 
Demyelination is common in spinal cord injury and disease states such 
as Multiple Sclerosis, and interferes with signal conduction between 
the neurons. Human cells from adult have been used to treat animal 
models of disease states . For example, human cells led to functional 
improvement in animal models of Parkinson's disease using human bone 
cells \28\ or using neural stem cells.\29\ Human brain adult stem cells 
can even be obtained after death \30\ so if a person's own stem cells 
are not used; there are other less objectionable alternatives. Another 
alternative to the use of embryonic stem cells is human umbilical cord 
blood. Human umbilical cord blood has the potential to form 
neurons,\31\ \32\ as well as other cell types.\33\ Human umbilical cord 
blood injected IV caused a functional improvement when injected into 
experimental animals with traumatic brain injury or stroke.\34\ \35\ In 
the case of genetic defects, there are several other alternatives to 
cloning. One is gene therapy that has been successfully used in mice 
\36\ and humans. More recently stem cells have been used as vehicle to 
deliver genes to the brain.\37\ \38\ \39\ \40\. Bone marrow stromal 
cells from adult rats promote functional recovery after spinal cord 
injury in rats when given 1 week after injury,\41\ even when the cells 
are injected intravenously.\42\ Bone marrow stromal cells also will 
migrate to site of a head injury when given IV and caused a functional 
improvement.\43\
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    \26\ Shihabuddin L.S., Horner P.J., Ray J., Gage F.H. Adult spinal 
cord stem cells generate neurons after transplantation in the adult 
dentate gyrus. Journal of Neuroscience. 20(23):8727-35, 2000.
    \27\ Akiyama Y., Honmou O., Kato T., Uede T., Hashi K., Kocsis 
J.D.: Transplantation of clonal neural precursor cells derived from 
adult human brain establishes functional peripheral myelin in the rat 
spinal cord. Exp Neurol 167:27-39, 2001.
    \28\ Hou L.L., Zheng M., Wang D.M., Yuan H.F., Li H.M., Chen L., 
Bai C.X., Zhang Y., Pei X.T.[Migration and differentiation of human 
bone marrow mesenchymal stem cells in the rat brain].Sheng Li Hsueh 
Pao--Acta Physiologica Sinica. 55(2):153-9, 2003.
    \29\ Liker M.A., Petzinger G.M., Nixon K., McNeill T., Jakowec M.W. 
Human neural stem cell transplantation in the MPTP-lesioned mouse. 
Brain Research. 971(2):168-77, 2003.
    \30\ Palmer T.D., Schwartz P.H., Taupin P., Kaspar B., Stein S.A., 
Gage F.H. Cell culture. Progenitor cells from human brain after death. 
Nature. 411(6833):42-3, 2001.
    \31\ Sanchez-Ramos J.R., Song S., Kamath S.G., Zigova T., Willing 
A., Cardozo-Pelaez F., Stedeford T., Chopp M., Sanberg P.R. Expression 
of neural markers in human umbilical cord blood. Experimental 
Neurology. 171(1):109-15, 2001.
    \32\ BuzaAska L., Stachowiak E., Stachowiak M., DomaAska-Janik K. 
Neural stem cell line derived from human umbilical cord blood--
morphological and functional properties.Journal of Neurochemistry. 85 
Suppl 2:33, 2003.
    \33\ Goodwin H.S., Bicknese A.R., Chien S.N., Bogucki B.D., Quinn 
C.O., Wall D.A. Multilineage differentiation activity by cells isolated 
from umbilical cord blood: expression of bone, fat, and neural markers. 
Biology of Blood & Marrow Transplantation. 7(11):581-8, 2001.
    \34\ Lu D., Sanberg P.R., Mahmood A., Li Y., Wang L., Sanchez-Ramos 
J., Chopp M. Intravenous administration of human umbilical cord blood 
reduces neurological deficit in the rat after traumatic brain 
injury.Cell Transplantation. 11(3):275-81, 2002.
    \35\ Sanberg P.R., Chopp M., Willing A.E., Zigova T., Saporta S., 
Song S., Bickford P., Garbuzova-Davis S., Newman M., Cameron D.F., 
Sanchez-Ramos J. Potential of umbilical cord blood cells for brain 
repair.Journal of Neurochemistry. 81 Suppl 1:83, 2002.
    \36\ Shen J.S., Watabe K., Ohashi T., Eto Y. Intraventricular 
administration of recombinant adenovirus to neonatal twitcher mouse 
leads to clinicopathological improvements. Gene Therapy. 8(14):1081-7, 
2001.
    \37\ Schwarz E.J., Reger R.L., Alexander G.M., Class R., Azizi 
S.A., Prockop D.J. Rat marrow stromal cells rapidly transduced with a 
self-inactivating retrovirus synthesize L-DOPA in vitro. Gene Therapy. 
8(16):1214-23, 2001.
    \38\ Nakano K., Migita M., Mochizuki H., Shimada T. Differentiation 
of transplanted bone marrow cells in the adult mouse brain. 
Transplantation. 71(12):1735-40, 2001.
    \39\ Park K.W., Eglitis M.A., Mouradian M.M. Protection of nigral 
neurons by GDNF-engineered marrow cell transplantation. Neuroscience 
Research. 40(4):315-23, 2001.
    \40\ Ehtesham M., Kabos P., Gutierrez M.A., Chung N.H., Griffith 
T.S., Black K.L., Yu J.S. Induction of glioblastoma apoptosis using 
neural stem cell-mediated delivery of tumor necrosis factor-related 
apoptosis-inducing ligand. Cancer Research. 62(24):7170-4, 2002l.
    \41\ Hofstetter C.P., Schwarz E.J., Hess D., Widenfalk J., El 
Manira A., Prockop D.J., Olson L. Marrow stromal cells form guiding 
strands in the injured spinal cord and promote recovery. Proceedings of 
the National Academy of Sciences of the United States of America. 
99(4):2199-204, 2002.
    \42\ Akiyama Y., Radtke C., Honmou O., Kocsis J.D. Remyelination of 
the spinal cord following intravenous delivery of bone marrow cells. 
[Journal Article] GLIA. 39(3):229-36, 2002.
    \43\ Lu D., Mahmood A., Wang L., Li Y., Lu M., Chopp M. (2001) 
Adult bone marrow stromal cells administered intravenously to rats 
after traumatic brain injury migrate into brain and improve 
neurological outcome. Neuroreport 12:559-63.
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    Below is a brief summary (in italics) of recent findings using 
other treatments besides stem cell for injuries and diseases of the 
nervous system. This summary is meant to make 2 major points:

  (1)  Other treatments used alone or in combination with adult stem 
        cells may hold the greatest promise in treating spinal cord 
        injury and other damage to the nervous system.

  (2)  While there is no ban on animal cloning, a review of recent 
        literature revealed more than 40 articles of promising 
        treatments other than stem cells for spinal cord injury but 
        only 1 or just a few articles showing any therapeutic benefit 
        of therapeutic cloning. The one article that received 
        significant press coverage attempted to show a benefit of 
        cloning in an animal study also revealed some of the 
        difficulties with this procedure.\44\
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    \44\ Rideout W.M. III, Hochedlinger K., Kyba, M. Daley Q., and 
Jaenisch R. Correction of a genetic defect by nuclear transplantation 
and combined cell and gene therapy Cell 109:17-27

    Other cell types: Other cell types that do not form neurons also 
help in recovery. After selective demyelination in rat spinal cord, 
olfactory ensheathing cells myelinated axons \45\ and led to greater 
motor and somatosensory evoked potentials and a better functional 
outcome.\46\ Olfactory ensheathing cells promote locomotor recovery in 
the transected cord after delayed transplantation.\47\ These cells were 
also found to stimulate growth of motor axons.\48\ Olfactory 
ensheathing cells when used with methylprednisolone promoted functional 
recovery and axonal regeneration after lesioning of the corticospinal 
tract.\49\
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    \45\ Kato T., Honmou O., Uede T., Hashi K., Kocsis J.D. 
Transplantation of human olfactory ensheathing cells elicits 
remyelination of demyelinated rat spinal cord. GLIA. 30(3):209-18, 
2000.
    \46\ VerdA E., GarcA-a-AlA-as G., ForA(C)s J., LA pez-Vales R., 
Navarro X. Olfactory ensheathing cells transplanted in lesioned spinal 
cord prevent loss of spinal cord parenchyma and promote functional 
recovery GLIA. 42(3):275-86, 2003.
    \47\ Lu J., Feron F., Mackay-Sim A., Waite P.M. Olfactory 
ensheathing cells promote locomotor recovery after delayed 
transplantation into transected spinal cord. Brain 125:14-21, 2002.
    \48\ Ramon-Cueto A., Cordero M.I., Santos-Benito F.F., Avila J. 
Functional recovery of paraplegic rats and motor axon regeneration in 
their spinal cords by olfactory ensheathing glia. Neuron 2000 
Feb;25(2):425-35.
    \49\ Nash H.H., Borke R.C., Anders J.J. Ensheathing cells and 
methylprednisolone promote axonal regeneration and functional recovery 
in the lesioned adult rat spinal cord. Journal of Neuroscience. 
22(16):7111-20, 2002.
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    Growth Factors: With the discovery of new growth factors such as 
neurotrophic factors and cytokines that influence the survival and 
growth of neurons, it was hoped that spinal cord injury could soon be 
treated. Brain-derived neurotrophic factor (BDNF) reduces the necrotic 
zone and supports neuronal survival after spinal cord hemisection in 
adult rats \50\ and suppresses apoptosis of oligodendrocytes.\51\ Also 
neurotrophin-3 (NT-3) enhances sprouting of corticospinal tract after 
adult spinal cord lesion \52\ even in chronic SCI.\53\ Basic fibroblast 
growth factor (bFGF) reduced the pathology observed in spinal cord 
injured rats receiving bFGF via the CSF following a spinal cord 
injury.\54\ Acidic fibroblast growth factor (aFGF) promote axonal 
growth between spinal cord slices \55\ and when combined with 
peripheral nerve segments led to improved locomotor function after 
spinal transection.\56\ Insulin growth factor 1 (IGF-1) stimulates 
myelin formation in the nervous system \57\ and also stimulates the 
production of neurons and synapse formation.\58\ In our own lab studies 
using cells derived from adult stem cells to treat rats with severe, 
chronic spinal cord injuries, significant functional improvement was 
observed when the factors (diff media) used for stem cells maturation 
are used alone. Further improvements are found when adult stem cell 
(SC) or IGF-1 is added to the treatment suggesting the benefit of 
combination treatments.
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    \50\ Novikova L., Novikov L., Kellerth J.O. Brain-derived 
neurotrophic factor reduces necrotic zone and supports neuronal 
survival after spinal cord hemisection in adult rats. Neuroscience 
Letters. 220(3):203-6, 1996.
    \51\ Koda M., Murakami M., Ino H., Yoshinaga K., Ikeda O., 
Hashimoto M., Yamazaki M., Nakayama C., Moriya H. Brain-derived 
neurotrophic factor suppresses delayed apoptosis of oligodendrocytes 
after spinal cord injury in rats. Journal of Neurotrauma. 19(6):777-85, 
2002.
    \52\ Schnell, L., R. Schneider, R. Kolbeck, Y.A. Bard and M.E. 
Schwab (1994) Neurotrophin-3 enhances sprouting of corticospinal tract 
during development and after adult spinal cord lesion. Nature 367:170-
173.
    \53\ Tuszynski M.H., Grill R., Jones L.L., Brant A., Blesch A., 
L.A. w K., Lacroix S., Lu P. NT-3 gene delivery elicits growth of 
chronically injured corticospinal axons and modestly improves 
functional deficits after chronic scar resection. Experimental 
Neurology. 181(1):47-56, 2003.
    \54\ Liu W.G., Luo Y.X. The early protective effects of basic 
fibroblast growth factor on acute spinal cord injury in rats. 
[Chinese]Chung-Kuo Hsiu Fu Chung Chien Wai Ko Tsa Chih/Chinese Journal 
of Reparative & Reconstructive Surgery. 13(5):291-4, 1999.
    \55\ Lee Y.S., Baratta J., Yu J., Lin V.W., Robertson R.T. AFGF 
promotes axonal growth in rat spinal cord organotypic slice co-
cultures. Journal of Neurotrauma. 19(3):357-67, 2002.
    \56\ Lee Y.S., Hsiao I., Lin V.W. Peripheral nerve grafts and aFGF 
restore partial hindlimb function in adult paraplegic rats. Journal of 
Neurotrauma. 19(10):1203-16, 2002.
    \57\ Brooker G.J., Kalloniatis M., Russo V.C., Murphy M., Werther 
G.A., Bartlett P.F. Endogenous IGF-1 regulates the neuronal 
differentiation of adult stem cells. J. Neurosci. Res. 59(3):332-41, 
2000.
    \58\ O'Kusky J.R., Ye P., D'Ercole A.J. Insulin-like growth factor-
I promotes neurogenesis and synaptogenesis in the hippocampal dentate 
gyrus during postnatal development. Journal of Neuroscience. 
20(22):8435-42, 2000.



    Another cytokine, transforming growth factor-beta (TGF-beta) caused 
a decrease in the lesion size following SCI.\59\ Yet another cytokine, 
glial cell line-derived neurotrophic factor (GDNF) when incorporated in 
a fibrin glue promotes dorsal root regeneration into spinal cord.\60\ 
Metabolites such as inosine also appear to encourage growth of spared 
axons and possibly injured axons following spinal cord injury.\61\ The 
spinal cord distal to the injury consists of cells that are shrunken 
and appear unhealthy. One possibility is that this natural metabolite 
especially when used as part of a combination treatment may stimulate 
the growth of these cells. Many recent studies have used a combination 
of growth factors. The combination of EGF and bFGF showed better 
functional recovery than vehicle or either factor alone.\62\ Insulin-
like growth factor (IGF) and epidermal growth factor (EGF) rescued 
motor neurons better than each individually even when delivered after 
4-week delay.\63\ Although significant stimulation of axonal growth is 
observed with growth factors, problems in delivery, penetration, and 
down-regulation or truncation of receptors \64\ have perhaps kept their 
full potential from being realized.
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    \59\ Tyor W.R., Avgeropoulos N., Ohlandt G., Hogan E.L. Treatment 
of spinal cord impact injury in the rat with transforming growth 
factor-beta. Journal of the Neurological Sciences. 200(1-2):33-41, 
2002.
    \60\ Iwakawa M., Mizoi K., Tessler A., Itoh Y. Intraspinal implants 
of fibrin glue containing glial cell line-derived neurotrophic factor 
promote dorsal root regeneration into spinal cord. Neurorehabilitation 
& Neural Repair. 15(3):173-82, 2001.
    \61\ Benowitz L.I., D.E. Goldberg, J.R. Madsen, D. Soni and N. 
Irwin Inosine stimulates extensive axon collateral growth in the rat 
corticospinal tract after injury. PNAS 96: 13486-13490, 1999.
    \62\ Kojima A., Tator C.H. Intrathecal administration of epidermal 
growth factor and fibroblast growth factor 2 promotes ependymal 
proliferation and functional recovery after spinal cord injury in adult 
rats. Journal of Neurotrauma. 19(2):223-38, 2002.
    \63\ Bilak M.M., Kuncl R.W. Delayed application of IGF-I and GDNF 
can rescue already injured postnatal motor neurons. Neuroreport. 
12(11):2531-5, 2001.
    \64\ Liebl D.J., Huang W., Young W., Parada L.F. Regulation of Trk 
receptors following contusion of the rat spinal cord.Experimental 
Neurology. 167(1):15-26, 2001.
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    Gene therapies: To overcome the problem of the growth factors 
actually reaching the affected neurons, two strategies have been taken. 
First, certain cell types have been modified to produce growth factors 
then grafted into the injury site. Second, endogenous cells have been 
genetically modified primarily using virus vectors. Fibroblasts 
genetically modified to produce BDNF \65\ or NGF \66\ support regrowth 
of chronically injured axons. The in vivo transfer of GDNF cDNA can 
promote axonal regeneration and enhance locomotion functional 
recovery.\67\ Neurotrophin-secreting Schwann cell implants improved 
urinary bladder structure after spinal cord contusion.\68\ NT-3 gene in 
an adenoviral vector was delivered to the spinal motoneurons by 
retrograde transport through the sciatic nerve, causing induced growth 
of axons from the intact corticospinal tract across the midline to the 
denervated side.\69\ Another approach is to actually stimulate one of 
the intracellular pathways that play a role in neurite outgrowth. Viral 
delivery of vectors carrying the mutated form of MEK1 that activates of 
the extracellular-signal-regulated kinases (ERKs) induces axonal 
regeneration across the transection site of the spinal cord in young 
rats.\70\ Newer approaches that direct transient production of growth 
factors specifically in motor neurons also hold great promise.\71\
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    \65\ Jin Y., Tessler A., Fischer I., Houle J.D. Fibroblasts 
genetically modified to produce BDNF support regrowth of chronically 
injured serotonergic axons.Neurorehabilitation & Neural Repair. 
14(4):311-7, 2000.
    \66\ Grill R.J., A. Blesch and M.H. Tuszynski (1997). Robust growth 
of chronically injured spinal cord axons induced by grafts of 
genetically modified NGF-secreting cells. Exper. Neurol. 148:44-452.
    \67\ Lu K.W., Chen Z.Y., Jin D.D., Hou T.S., Cao L., Fu Q. Cationic 
liposome-mediated GDNF gene transfer after spinal cord injury. Journal 
of Neurotrauma. 19(9):1081-90, 2002.
    \68\ Sakamoto K., Uvelius B., Khan T., Damaser M.S. Preliminary 
study of a genetically engineered spinal cord implant on urinary 
bladder after experimental spinal cord injury in rats. Journal of 
Rehabilitation Research & Development. 39(3):347-57, 2002.
    \69\ Zhou L., Baumgartner B.J., Hill-Felberg S.J., McGowen L.R., 
Shine H.D. Neurotrophin-3 expressed in situ induces axonal plasticity 
in the adult injured spinal cord.Journal of Neuroscience. 23(4):1424-
31, 2003.
    \70\ Miura T., Tanaka S., Seichi A., Arai M., Goto T., Katagiri H., 
Asano T., Oda H., Nakamura K. Partial functional recovery of paraplegic 
rat by adenovirus-mediated gene delivery of constitutively active 
MEK1.Experimental Neurology. 166(1):115-26, 2000.
    \71\ Jackson, C.A., C. Cobbs, J.D. Peduzzi, M. Novak and C.D. 
Morrow (2001) Repetitive Intrathecal injections of Poliovirus Replicons 
result in gene expression in neurons of the central nervous system 
without pathogenesis. Human Gene Therapy, 12:1827-1842.
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    Substrate or Matrix: There have been several studies that provide a 
substrate for growth is useful. Self-assembling peptide scaffolds 
support differentiation as well as extensive neurite outgrowth in 
culture.\72\ When a collagen tube is implanted into hemisected adult 
rat spinal cord, there is growth of the rostral spinal axons into the 
caudal ventral roots.\73\ Growth factor-treated nitrocellulose implants 
that bridge a complete transection lesion of adult rat spinal cord 
caused regrowth of ascending sensory axons across the traumatic spinal 
cord injury site.\74\ Implants using poly-beta-hydroxybutyrate (PHB) as 
carrier scaffold and containing alginate hydrogel, fibronectin, and 
Schwann cells can support neuronal survival and regeneration after 
spinal cord injury.\75\ Using a polymer scaffold seeded with stem cells 
led to better functional recovery in hemisected SC and appeared to 
encourage the growth of corticospinal axons.\76\ When a hydrogel is 
implanted into the injury site of a rat with chronic, severe SCI, there 
was improved function and evidence of blood vessels, and axonal 
growth.\77\
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    \72\ Holmes T.C., de Lacalle S., Su X., Liu G., Rich A., Zhang S. 
(2000) Extensive neurite outgrowth and active synapse formation on 
self-assembling peptide scaffolds. PNAS 97:6728-33.
    \73\ Liu S., Said G., Tadie M. Regrowth of the rostral spinal axons 
into the caudal ventral roots through a collagen tube implanted into 
hemisected adult rat spinal cord. Neurosurg. 49:143-50, 2001.
    \74\ Houle J.D. and M.K. Ziegler (1994) Bridging a complete 
transection lesion of adult rat spinal cord with growth factor-treated 
nitrocellulose implants. J. Neural Transplant. & Plast. 5:1115-124.
    \75\ Novikov L.N., Novikova L.N., Mosahebi A., Wiberg M., Terenghi 
G., Kellerth J.O. A novel biodegradable implant for neuronal rescue and 
regeneration after spinal cord injury. Biomaterials. 23(16):3369-76, 
2002.
    \76\ Teng Y.D., Lavik E.B., Qu X.. Park K.I., Ourednik J., 
Zurakowski D., Langer R., Snyder E.Y. Functional recovery following 
traumatic spinal cord injury mediated by a unique polymer scaffold 
seeded with neural stem cells. Proceedings of the National Academy of 
Sciences of the United States of America. 99(5):3024-9, 20.
    \77\ Woerly S., Doan V.D., Evans-Martin F., Paramore C.G., Peduzzi 
J.D. Spinal cord reconstruction using NeuroGel implants and functional 
recovery after chronic injury.Journal of Neuroscience Research. 
66(6):1187-97, 2001.
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    Modifying the Immune System: The immune system plays an important 
role in spinal cord injury. Many cytokines and other factors released 
by immune cells also influence neural cells. Several studies suggest a 
benefit of activated macrophages or specific T cells in reducing the 
amount of secondary injury and stimulating growth after spinal cord 
injury in rats.\78\ Recent clinical trials using activated macrophages 
are being conducted in Israel.\79\ However, others have found that 
activation of macrophages in a normal cord can actually cause axonal 
injury and demyelination \80\ and suggests inherent danger of 
activating the immune system after SCI.\81\ IL-10 is neuroprotective 
after a spinal cord injury.\82\ Another study found that IL-10 and MPS 
reduce the amount of damaged tissue but do not change functional 
outcome.\83\
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    \78\ Hauben E., Agranov E., Gothilf A., Nevo U., Cohen A., Smirnov 
I., Steinman L., Schwartz M. Posttraumatic therapeutic vaccination with 
modified myelin self-antigen prevents complete paralysis while avoiding 
autoimmune disease. Journal of Clinical Investigation. 108(4):591-9, 
2001.
    \79\ http://www.biospace.com/company_profile.cfm?CompanyID=4350
    \80\ Popovich P.G., Guan Z., McGaughy V., Fisher L., Hickey W.F., 
Basso D.M. The neuropathological and behavioral consequences of 
intraspinal microglial/macrophage activation. Journal of Neuropathology 
& Experimental Neurology. 61(7): 623-33, 2002.
    \81\ Jones T.B., Basso D.M., Sodhi A., Pan J.Z., Hart R.P., 
MacCallum R.C., Lee S., Whitacre C.C., Popovich P.G. Pathological CNS 
autoimmune disease triggered by traumatic spinal cord injury: 
implications for autoimmune vaccine therapy. Journal of Neuroscience. 
22(7):2690-700, 2002.
    \82\ Bethea J.R., Nagashima H., Acosta M.C., Briceno C., Gomez F., 
Marcillo A.E., Loor K., Green J., Dietrich W.D. Systemically 
administered interleukin-10 reduces tumor necrosis factor-alpha 
production and significantly improves functional recovery following 
traumatic spinal cord injury in rats. [Journal Article] Journal of 
Neurotrauma. 16(10):851-63, 1999.
    \83\ Takami T., Oudega M., Bethea J.R., Wood P.M., Kleitman N., 
Bunge M.B. Methylprednisolone and interleukin-10 reduce gray matter 
damage in the contused Fischer rat thoracic spinal cord but do not 
improve functional outcome. Journal of Neurotrauma. 19(5):653-66, 2002.
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    Inhibitors and Scar: For many years, Schwab and colleagues explored 
the potential of the IN-1 antibody to block myelin associated 
inhibitory molecule, Nogo, after SCI. IN-1 caused improvement in 
function if given shortly after injury.\84\ Other myelin-associated 
inhibitors such as MAG have been described. Blockers of Nogo and MAG 
appear to cause functional improvement.\85\ Many suggest that the scar 
inhibits \86\ and have tried various inhibitors such as iron 
chelators.\87\ Beta-aminopropionitrile treatment that inhibits the 
formation of glial scar accelerates recovery of mice after spinal cord 
injury.\88\ Other efforts involve implantation of a collagen tube to 
interfere with scar formation.\89\ The semaphorins may be important 
contributor to the inhibitory effects of the scar.\90\
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    \84\ Merkler D., Metz G.A., Raineteau O., Dietz V., Schwab M.E. 
Fouad K.Locomotor recovery in spinal cord-injured rats treated with an 
antibody neutralizing the myelin-associated neurite growth inhibitor 
Nogo-A.Journal of Neuroscience. 21(10):3665-73, 2001.
    \85\ GrandPre T., Li S., Strittmatter S.M. Nogo-66 receptor 
antagonist peptide promotes axonal regeneration. Nature. 417(6888): 
547-51, 2002.
    \86\ Hermanns S., Klapka N., Muller H.W. The collagenous lesion 
scar--an obstacle for axonal regeneration in brain and spinal cord 
injury.Restorative Neurology & Neuroscience. 19(1-2):139-48, 2001.
    \87\ Hermanns S., Reiprich P., Muller H.W. A reliable method to 
reduce collagen scar formation in the lesioned rat spinal cord.Journal 
of Neuroscience Methods. 110(1-2):141-6, 2001.
    \88\ Gilad G.M., Gilad V.H. Beta-aminopropionitrile treatment can 
accelerate recovery of mice after spinal cord injury.European Journal 
of Pharmacology. 430(1):69-72, 2001.
    \89\ Spilker M.H., Yannas I.V., Kostyk S.K., Norregaard T.V., Hsu 
H.P., Spector M. The effects of tubulation on healing and scar 
formation after transection of the adult rat spinal cord. Restorative 
Neurology & Neuroscience. 18(1):23-38, 2001.
    \90\ Pasterkamp R.J., Anderson P.N., Verhaagen J. Peripheral nerve 
injury fails to induce growth of lesioned ascending dorsal column axons 
into spinal cord scar tissue expressing the axon repellent 
Semaphorin3A.European Journal of Neuroscience. 13(3):457-71, 2001.
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    Rehabilitation: There has been tremendous progress in the field of 
rehabilitation with use of weight-supported treadmills,\91\ functional 
electrical stimulation and biofeedback. In our own lab, we found a 
statistically significant improvement in rats with a moderate degree of 
spinal cord injury that are placed in an enriched environment compared 
to standard caging.\92\ An enriched environment consists of a social 
environment where there is free access to novel items that include 
exercise equipment.
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    \91\ 6. Edgerton V.R., Roy R.R., Hodgson J.A., Prober R.J., de 
Guzman C.P., de Leon R. Potential of adult mammalian lumbosacral spinal 
cord to execute and acquire improved locomotion in the absence of 
supraspinal input. J. Neurotrauma. 9 Suppl 1:S119-28, 1992.
    \92\ Fischer, F.R. and J.D. Peduzzi. Functional improvement in rats 
with chronic spinal cord injuries after exposure to an enriched 
environment. Soc. Neurosci. Abstr., 23:2188, 1997.
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    My primary reason for being here today is that I don't want victims 
of injuries and diseases to again become victims. The best chance of 
cellular treatment for them is using their own stem cells. Victims of 
injuries and diseases are again being used to justify a treatment that 
is not in their best interest. Both the clinical trials and pre-
clinical trials suggest that adult stem cells and/or using one's own 
stem cells is a more effective treatment for diseases and injuries. The 
data just keep accumulating that this is the direction to go despite 
the fact that most of the research is being done using embryonic stem 
cells in experimental animals or human cell lines.\93\ The least funded 
area is still `bench to bedside' research using one's own stem cells or 
using adult stem cells. Despite the fact that there are much fewer 
experimental studies using adult stem cells, amazing progress has been 
made as evidenced by the clinical trials. The idea that we should look 
to cloning for a treatment for diseases or injuries is way in the 
future. Despite all the claims of its promise there has been only 1 or 
2 experimental animal study to suggest that this is a promising 
direction.\94\ We have at least 200 experimental animal studies in the 
field of spinal cord injury alone that show that a particular cellular, 
growth factor, or other treatment causes a functional or anatomical 
improvement and only 1 or 2 in the field of cloning despite the fact 
that there is no ban on performing animal cloning. With only a limited 
amount of funding available, more focus is needed in directing research 
funds to areas that can help people in the next 5-10 years and not 
several lifetimes away.
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    \93\ Neil Munro. SCIENCE: Petri-Dish Politics. National Journal, 
04-19-2003.
    \94\ Rideout W.M. III, Hochedlinger K., Kyba M., Daley Q. and 
Jaenisch R. Correction of a genetic defect by nuclear transplantation 
and combined cell and gene therapy Cell 109:17-27.

    Senator Brownback. Thank you, Dr. Peduzzi.
    We have a vote on. First, I want to announce that I'll be 
joining other Members in a letter to promote and push for the 
funding for a national cord-blood bank system and the funding 
that you were talking about, Dr. Kurtzberg, that's going to be 
needed to do this. I know Senator Hatch is going to be joining 
in this letter, and I think we'll have several others. And 
we'll also be helping with legislation on a national cord-blood 
banking program. I think this has extraordinary opportunities, 
and I really applaud your work and Dr. Rubinstein's work that 
you're doing in this field that really holds so much promise. 
It's beautiful, beautiful work. And we'll be pushing for that 
to see if we can't get that mature on forward.
    This is very interesting to see and to hear, and exciting. 
I appreciate all of your passions and your help and your work 
that each of you are doing in this field.
    We've got a vote on that I'm going to move over for. And 
then what I think we'll do is, we'll bring the next panel up 
while I recess this for a period of time, and then bring that 
next panel up.
    But I hope, in the next year-and-a-half, we make as much 
progress as we made in the past year-and-a-half. I think you 
will see a fascinating array of people being treated and helped 
if we're able to put in the resources here, if we're able to 
really move forward in these fields of regenerative medicine. 
The adult work, the cord blood, has been beautiful in its 
successes and are really exciting to see these moving forward.
    We will be in recess for approximately 15 minutes. If I 
could have the next panel ready to go when I get back, and then 
we'll move forward.
    Thank the panelists for being here today.
    We're in recess for 15 minutes.
    [Recess.]
    Senator Brownback. Call the hearing back to order.
    I want to apologize for making it over and back so fast, I 
didn't have as much time to spend with those who wanted to 
visit with me.
    We've got an exciting next panel that I would like to call 
up. And the last panel was very informative, as well. These are 
patients, who have been working on and been involved in some 
really incredible things. Mr. Steven L. Barsh, from 
Pennsylvania; Mr. Keone Penn, from Snellville, Georgia; and Mr. 
Stephen R. Sprague, from Staten Island, New York, the people 
that will be testifying, and we look forward to hearing your 
comments and the testimony.
    I would say to each of you, we have your written testimony 
in the record, so you can summarize, if you'd like or you can 
go all go off this testimony, whichever you would like, or you 
can submit your written testimony for the record and then say 
what you please here. And then I look forward to being able to 
question each of you for a little bit, if possible.
    I thank you all very much for coming here, appreciate your 
being willing to attend. And, Ms. Penn, I appreciate you being 
willing to come, accompanying your son, here today, as well. 
Mr. Barsh, delighted to have you.

                 STATEMENT OF STEVEN L. BARSH, 
                  MERION STATION, PENNSYLVANIA

    Mr. Barsh. Thank you, Senator Brownback. And, by the way, 
do we have 5 minutes or 7 minutes for our testimony?
    Senator Brownback. I'm going to run the clock at 7 minutes, 
just to give you some guidance.
    Mr. Barsh. No problem.
    Senator Brownback. As you can see, it's not a hard and fast 
rule, but it gives you a little bit of guidance.
    Mr. Barsh. It's greatly appreciated. Unfortunately I'm not 
a patient; I'm a parent. Our son, Spencer, couldn't be here 
today. He's three and a half. It was too much for him to come 
down from Philadelphia, and he had some therapy this morning. 
So I'm just the parent of a patient. But good afternoon.
    Thank you for the opportunity to testify today on the very 
important topic of cord blood, and why a national cord-blood 
stem cell bank network should be provided for to save the lives 
of some of this great nation's most severely ill children and 
adults.
    We first learned, a little over 2 years ago, that our one-
year-old son, Spencer, had ALD, or adrenoleukodystrophy. In 50 
percent of ALD children, more and more of their brains vanish 
due to this rare neurodegenerative disease, leading to loss of 
function and death by age ten. The remaining 50 percent have a 
severe-to-deadly form as adults. A parent's worst nightmare, 
or, in this case, a day-mare, because you actually have to live 
through it. This is the disease behind the film, Lorenzo's Oil, 
if you're familiar with that film. As a matter of fact, 
Lorenzo's father is in this room today, a very great man.
    Senator Brownback. Would he care to stand so we could 
recognize him?
    Mr. Barsh. Oh, he's just stepped out. Augusto Odone. I'm 
sorry.
    Senator Brownback. Well, we'll try to recognize him when he 
comes back.
    Mr. Barsh. I apologize. He is present today. A very great 
man.
    Spencer, our son, started to have repeated MRI brain 
studies. In February of last year, these MRI studies showed 
changes had started in his brain, indicating that the deadly 
brain deterioration had begun.
    Cord-blood and bone-marrow transplants are the only 
accepted therapies when this ALD brain deterioration begins and 
is caught in time, as Dr. Kurtzberg referenced. You need to 
catch these diseases in time.
    Via the National Marrow Donor Program, or the NMDP, we 
searched for a perfect six-out-of-six bone-marrow match, and 
couldn't find one. And, as some of the doctors or researchers 
alluded to earlier, finding a good match is really important. 
Otherwise, particularly in bone marrow, it doesn't work real 
well and it has a pretty poor outcome, to put it mildly. Plus, 
we were looking at nearly 6 months before we could even get 
Spencer to transplant, while his brain would continue to break 
down and deteriorate, because going the bone-marrow route takes 
a lot of time.
    See, even if you find someone on the National Marrow Donor 
Program donor list, it doesn't mean you can get to them 
quickly. It's a heartbreaking and gut-wrenching process of 
calling in potential donors that they identify through their 
network, having them screened, confirming that they'll go 
through surgery to remove some of their bone marrow, et cetera. 
You lose precious time waiting. And in these neurodegenerative 
diseases, it's a time issue. You really need to transplant 
very, very quickly. Worse yet, more than 50 percent of people 
are turned away by the NMDP, told there's no suitable donor for 
them. So about, you know, 50 to 60 of every 100 people that 
knock on their door looking for a solution are told, ``Sorry, 
we can't help you.''
    ALD, like many metabolic diseases, can move very quickly 
along its destructive path, and horrifying changes can often be 
seen daily in your child. This is particularly true for rare 
metabolic diseases discussed earlier, such as Hurlers, MLD, or 
metachromatic leukodystrophy, Tay-Sachs, and others--all 
diseases that can now be treated by a cord-blood transplant.
    In metabolic diseases, lessening the time to transplant 
equals less deficits and a better transplant outcome. As 
discussed, time is enemy number one. And, in cord blood, the 
unit has already been typed, checked, prepped, and is waiting 
in a freezer right now. There just needs to be more of it.
    Spencer's pre-transplant work-up testing started just 4 
weeks after we found a bad MRI of his brain, and only 5 days 
after my wife and I made the decision that he should be 
transplanted. There was no 6 months of waiting. We held on 
tightly to our two-and-a-half-year-old son, Spencer, while he 
was in a pediatric isolation and intensive-care unit for nearly 
40 days. There, he received his cord-blood stem cell 
transplant, preceded by highly toxic medications, including 
massive, massive chemotherapy. He was lucky. He had what's been 
considered and characterized an ``easy course of transplant.''
    At the same time, we saw kids who didn't make it, as the 
procedure proved too toxic. While core-blood stem cells work 
for most of their very, very fortunate recipients, more 
research needs to be done. More and higher-quality cord-blood 
units need to be available, not only for transplantation, but 
for research purposes. And stem cell research, in general, 
needs to be carefully and properly further explored to harness 
all of its life-saving potential. Those greater units and 
greater research, particularly in cord blood, would come about 
by passage of this bill.
    Spencer's cord-blood transplant was just 14 months ago. But 
who's counting? He's doing extremely well. As a matter of fact, 
I'm happy to say he starts summer camp in 2 weeks. It'll be his 
first time he ever goes to camp, school, nursery school, 
anything, in his entire life. And he'll walk into that camp as 
a normal little boy.
    We see improvements and problem reversal on a weekly basis. 
At only 6 months post-transplant, physicians began to see 
improvements in Spencer's brain MRI, as well as his clinical 
presentation. It appears that Spencer is actually re-
myelinating, meaning that the cord-blood stem cells are 
repairing his brain. The early progenitor stem cells from the 
cord blood are differentiating into other cell types.
    The MRI and clinical observations have been confirmed both 
at Duke and by a diverse team at Children's Hospital of 
Philadelphia, or CHOP. I believe the non-technical word they 
have used is ``amazing,'' going on to say, ``We've never seen 
anything like this. We don't usually see brain MRIs improve.''
    Cord blood works. With only one-tenth of the funding 
provided to the National Marrow Donor Program today, cord blood 
from a national cord-blood stem cell bank network is a solution 
for more than the 50 percent of people who the NMDP turns away. 
These treatment options must be available to the children and 
adults who have these devastating diseases, including malignant 
diseases, such as leukemias.
    In closing, it's important to remember that you can get to 
transplant with cord blood extremely quickly, which is very, 
very critical with many diseases. The early progenitor stem 
cells in Spencer now appear to be differentiating into other 
cell types and are repairing problems in his brain. ``Just 
amazing'' is the term we hear time and again.
    At only one-tenth of the funding provided to the NMDP, a 
national cord-blood stem cell bank network can be provided so 
that this life-saving technology, that works today, can be 
available to everyone in need.
    We now have a normal and healthy 3-year-old son. His name 
is Spencer Barsh. And cord blood saved his life.
    Thank you for your time and thoughtful consideration on 
this matter.
    [The prepared statement of Mr. Barsh follows:]

  Prepared Statement of Steven L. Barsh, Merion Station, Pennsylvania

    Good afternoon.
    Thank you for the opportunity to testify today on the very 
important topic of cord blood and why a National Cord Blood Stem Cell 
Bank Network should be provided for to save the lives of some of this 
great nation's most severely ill children and adults.
    We first learned a little over 2 years ago that our one year old 
son Spencer had ALD or Adrenoleukodystrophy. Fifty percent of ALD 
children have a deadly cerebral onset of this rare neurodegenerative 
disease leading to loss of function and death by age 10. The remaining 
50 percent have a severe to deadly form as adults. A parent's worst 
nightmare, this is the disease behind the film Lorenzo's Oil.
    Spencer started to have repeated MRI brain studies and in February 
of last year, MRI studies showed changes had started in his brain 
indicating a deadly cerebral onset had begun.
    Cord blood and bone marrow transplants are the only ``accepted'' 
therapies when a cerebral onset of ALD has begun and is caught in time.
    Via the National Marrow Donor Program (NMDP) we had already been 
searching for a perfect 6/6 bone marrow match and couldn't find one. 
Plus, we were looking at nearly 6 months before we could even get to 
transplant while Spencer would be deteriorating.
    Even if you find someone on the NMDP donor list, it doesn't mean 
you can get to them quickly. It's a heartbreaking and gut-wrenching 
process of calling in potential donors, having them screened, 
confirming they will go through surgery, etc. You lose precious time, 
waiting. Worse yet, more than 50 percent of people are turned away told 
there is no suitable donor for them.
    ALD, like many metabolic diseases, can move very quickly along its 
destructive path and deficit changes can sometimes be seen daily. This 
is particularly true for rare metabolic diseases such as Hurler's, MLD, 
Tay-Sachs, and others--all diseases that can now be treated by a cord 
blood transplant.
    In metabolic diseases, lessening the time to transplant equals less 
deficits and a better transplant outcome. Time is enemy #1. In cord 
blood, the unit has already been typed, checked, prepped, and is 
waiting in a freezer right now.
    Spencer's pre-transplant work-up testing started just 4 weeks after 
his bad MRI (only 5 days after my wife and I made the decision that he 
should be transplanted). There was no 6 months of waiting.
    We held on tightly to our 2\1/2\-year-old son Spencer while he was 
in a pediatric isolation and intensive care unit for nearly 40 days. 
There he received his cord blood stem cell transplant preceded by 
highly toxic medications including massive chemotherapy. He was lucky. 
He had what was considered an ``easy course of transplant.''
    At the same time, we saw kids who didn't make it as the procedure 
proved too toxic. While cord blood stem cells work for most of their 
very fortunate recipients, more research needs to be done. More and 
higher quality cord blood units need to be available not only for 
transplantation, but for research purposes; and stem cell research in 
general needs to be carefully and properly further explored to harness 
all of its life saving potential.
    His cord blood transplant was just 13 months ago, but who's 
counting?
    He is doing extremely well.
    We see improvements and deficit reversal on a weekly basis. At only 
6 months post transplant, physicians began to see improvements in 
Spencer's MRIs as well as clinical presentation.
    It appears that Spencer is actually re-myelinating as the early 
progenitor stems cells from the cord blood are differentiating into 
other cells types in his brain.
    The MRI and clinical observations have been confirmed both at Duke 
and by a diverse team at the Children's Hospital of Philadelphia 
(CHOP). I believe that the non-technical word they have used was 
``amazing'' going on to say ``They've never seen anything like this. We 
usually don't see MRIs improve.''
    Cord blood works.
    With only \1/10\ of the funding provided to the NMDP today, cord 
blood from a National Cord Blood Stem Cell Bank Network is a solution 
for the more than 50 percent of people who the NMDP turns away.
    These treatment options must be available to the children and 
adults who have these devastating diseases including malignant 
diseases.
    In closing:

   It's important to remember that you can get to transplant 
        with cord blood extremely quickly which is very, very critical 
        with many diseases.

   The early progenitor stem cells in Spencer now appear to be 
        differentiating into other cell types that are repairing 
        problems in his brain. ``Just amazing'' is the term we hear 
        time and again.

   At only 1/10th of the funding provided to the NMDP, A 
        National Cord Blood Stem Cell Bank Network can be provided for 
        so that this life saving technology, that works today, can be 
        available to everyone in need.
                  We now have a normal 3 year old son.
                       His name is Spencer Barsh.
                      Cord blood, saved his life.

    Thank you for your time and thoughtful consideration.

    Senator Brownback. Thank you for being here, Mr. Barsh. You 
know, when you talk about him going to summer camp, you amaze 
at the simple pleasures and what they truly mean. That's a 
beautiful story.
    Mr. Barsh. We cherish every day.
    Senator Brownback. Mr. Sprague, thank you very much for 
joining us here today, and I would turn to you next.

               STATEMENT OF STEPHEN R. SPRAGUE, 
                    STATEN ISLAND, NEW YORK

    Mr. Sprague. Thank you, Senator.
    I certainly am personally fortunate to have an opportunity 
to speak with you today; not in medical terms, but from a 
patient's perspective. I know you can't tell, but you're 
looking at an aging baby-boomer. And I was already a medical 
veteran before I got my leukemia diagnosis. That was 7 years 
ago. I was 47 years old. I was a diabetic. I had survived a 
heart attack and bypass surgery, all in 1993. In spite of all 
that medical training, I was totally unprepared for a battle 
with cancer.
    This was in November 1995. In those days, chemotherapy only 
stalled the inevitable for long-term survival, and that was, of 
course, the traditional bone-marrow transplant. ``The cure that 
can kill,'' we like to call it.
    Although CML, which was my diagnosis, usually progresses 
slowly, in May 1997, only 18 months after my initial diagnosis, 
I found myself in blast crisis, the end-stage of the disease.
    Meanwhile, my oncologist began what would quickly become a 
very frustrating marrow-donor search. I soon discovered that 
less than a third of those seeking transplant have a matching 
sibling, the best and most obvious donor source. I was an only 
child. I needed to find an unrelated donor if a transplant were 
even to be an option for me.
    To make a very long story short, I was not one of the lucky 
ones to find a match in any of the marrow-donor registries. 
``Enjoy your remission for as long as you can. Get your affairs 
in order,'' I remember them telling me, ``while we keep looking 
and try to figure something else out.''
    This sad predicament is still all too familiar for many 
adult leukemians. Even now, far too many patients are unable to 
proceed to transplant due to the complexity, as you've heard 
already earlier--the complexity of antigen matching, as well as 
the problems inherent in tracking down, collecting the matching 
marrow from a hopefully still willing and still available 
marrow donor.
    Fortunately, as I was, unfortunately, beginning to lose my 
remission, my doctor was planning to begin one of the very 
first clinical trials for end-stage adult CML'ers using 
neonatal stem cells, those from cord blood. A perfect cord-
blood match was found for me within days, from the New York 
Blood Center's world-renowned Placental Blood Program, as it 
was known back at that time. And in life-or-death struggles 
like these, days do matter.
    Incredibly, some still anonymous New York City mother had 
decided to do what few mothers were doing back then, and that 
was to donate her newborn cord blood to a public cord-blood 
bank. It was that donation, from that newborn baby girl, that 
just happened to be my one and my only stem cell match.
    I entered the hospital October 30, 1997. Magic and miracles 
happened. And, by the grace of God, I was discharged 40 
treacherous days later, but with a new, working immune system, 
no trace of leukemia. And no hair.
    [Laughter.]
    Mr. Sprague. Here I am today, 5 years, 7 months, and 12 
days later--and, believe me, I count every one of them--with a 
100 percent donor cells, all female chromosomes, just like my 
donor, completely cancer free. Still not much hair.
    [Laughter.]
    Mr. Sprague. In my post-transplant years as a patient 
advocate, I've come to learn a lot of things--about myself, 
about life and death, about perspectives, about appreciations 
and priorities, but, most importantly, about hope. Part of that 
hope, for desperate patients seeking transplant, patients like 
I was, involves options. Heading down the transplant trail is a 
risky endeavor, even in the best of circumstances, but that 
critical first step can't ever be taken without first finding 
the right stem cell match. Cord blood remains a largely 
untapped, non-controversial, readily available alternative 
source of non-embryonic stem cells.
    That's the good news. That most of it continues to be 
trashed as medical waste instead of finding its way into a 
public cord-blood bank, that remains the problem. But it's a 
solvable problem, as you've heard.
    Registering the good intentions of prospective volunteer 
marrow donors has been one solution to providing stem cells to 
patients in need. Collecting and preserving the actual cord 
blood, thanks to new parents who are willing, who are eager, to 
donate at the time of delivery, may be a better solution, or at 
least a viable option.
    As cord blood finds its way into the medical mainstream, 
it's my personal hope, shared by my cancer companions--the 
lucky ones like me, as well as the less fortunate ones, who 
have died waiting while searching for their elusive marrow 
match--that an infrastructure to assist patients nationwide can 
be created, regulated, funded to take better advantage of this 
natural and precious gift of life.
    If more of those estimated 4 million new parents each year 
have a better opportunity to donate their newborn's cord blood, 
an important new donor bank can be created quickly, 
conveniently, without pain and without controversy. And it 
certainly remains my privilege to serve as living proof of the 
promise of cord blood for the adult leukemia community.
    You know, we think of leukemia as a children's disease, but 
90 percent of all leukemia cases are diagnosed in middle-aged 
adults, like me, like some of you. Regardless of age, cord 
blood is a proven alternative for saving lives, that needs your 
support to become more readily available.
    Again, I thank you for the privilege of telling my story 
and sharing my concerns.
    [The prepared statement of Mr. Sprague follows:]

    Prepared Statement of Stephen R. Sprague, Cord Blood Crusader, 
                        Staten Island, New York

    Mr. Chairman and Members of the Subcommittee:

    My name is Stephen Sprague and I am personally fortunate to have 
the opportunity of speaking with you today. In a life before leukemia, 
I've appeared before lots of committees, but never about matters 
affecting life or death. Today, I'm here wearing a proud new hat . . . 
that of a long-term adult cord blood transplant survivor, and my 
remarks are much more critical . . . for those like me in the cancer 
community, and I hope, for you who have an opportunity to help us now . 
. . not with more research, but by supporting proven patient 
applications.
    While you probably can't tell, I'm an aging baby boomer and was 
already a medical veteran before I got my leukemia diagnosis 7 years 
ago at age 47. I'm a diabetic and had survived a heart attack and 
quadruple bypass surgery in 1993. In spite of that, I was totally 
unprepared for a battle with cancer. This was November 1995. In those 
days, and even today with new experimental wonder drugs for cancer, 
chemotherapy only stalled what was inevitable for long-term survival. . 
.the traditional bone marrow transplant. ``The Cure That Can Kill'' as 
some of us have learned to call it. Since CML is usually a slowly-
progressing, manageable cancer, I continued to seek a decent quality-
of-life while mentally preparing for transplant . . . the only option. 
For whatever reason, in May 1997, only 18 months after my initial 
diagnosis, I found myself in blast crisis, the end-stage of this 
disease.
    After a rigorous few months in the hospital, my oncologist, Dr. 
Andrew Pecora, got me into my first remission while we began what would 
quickly become a frustrating marrow donor search. I soon discovered 
that less than a third of those seeking transplant have a matching 
sibling, the best and most obvious donor source. Since I was an only 
child, I needed to find an unrelated matching donor if a transplant 
were to even be an option for me. To make a very long and complicated 
story short, I was not one of the lucky ones to find an acceptable 
match in any of the marrow donor registries. ``Enjoy your remission for 
as long as you can and get your affairs in order'' I was told, ``while 
we keep looking and try to figure something else out.''
    This sad predicament is still an all-too-familiar one for many 
adult leukemians. Even now, far too many patients referred for a 
primary marrow donor search are unable to actually proceed to 
transplant due to the complexity of antigen matching, as well as the 
problems inherent in tracking down and eventually collecting the 
matching marrow from a hopefully still-willing and still-available 
donor. Fortunately for me, there soon came a series of events that, to 
this day, I find difficult to understand or describe.
    Just as I was beginning to lose my remission, my doctor, who 
directs Hackensack (NJ) University Medical Center's prestigious Stem 
Cell Transplant Program, was planning to begin one of the very first 
clinical trials for end-stage adult CMLers using neonatal stem cells 
obtained from umbilical cord blood. And equally astonishing, a perfect 
cord blood match was found for me within days, from the New York Blood 
Center's world-renowned Placental Blood Program, as it was known at the 
time. And in life-or-death struggles like these, days matter. 
Incredibly, some still-anonymous New York City mother had decided to do 
what few new mothers were doing back in those days . . . donating their 
newborn's cord blood to a public cord blood bank. It was that donation 
from a newborn baby girl that happened to be my one and only match.
    I entered the hospital on October 30, 1997. Magic and miracles 
happened, including a pioneering treatment using cord blood. And by the 
grace of God, I was discharged 40 treacherous days later, December 8, 
1997, with a new, working immune system and no trace of leukemia. And 
no hair. Fast-forward a bit and here I am today . . . 5 years, 7 months 
and 12 days later . . . with 100 percent donor cells, all-female 
chromosomes just like my donor, completely cancer-free and in 
relatively good health. And still not much hair.
    In my post-transplant activities as a patient advocate volunteer, I 
have come to learn a lot of things. . .about myself, about life and 
death, and about perspectives, appreciations and priorities. And most 
importantly, about hope.
    My point is simply this. Part of that hope for desperate patients 
seeking transplant . . . patients like I was . . . involves options. 
Heading down the transplant trail is a risky endeavor, even in the best 
of circumstances. But that critical first step can't ever be taken 
without first finding the right stem cell match.
    As you will come to appreciate, umbilical cord blood remains a 
largely untapped, non-controversial and readily available alternative 
source of non-embryonic, neonatal stem cells. That's the good news. 
That most of it continues to be trashed as medical waste instead of 
finding its way into a public cord blood bank remains the problem. A 
solvable problem. Registering the good intentions of prospective 
volunteer marrow donors has been one solution to providing stem cells 
to patients in need. Collecting and preserving the actual cord blood 
thanks to new parents willing and eager to donate at the time of 
delivery may be a better one. Or at least another viable option.
    As cord blood finds its way into the medical mainstream, it is my 
personal hope, shared by my cancer companions . . . the lucky ones as 
well as the less fortunate ones who have died searching for their 
elusive marrow match . . . that an infrastructure to assist patients 
nationwide can be created, regulated and funded to take better 
advantage of this natural and precious ``gift of life.'' If more of 
those estimated 4 million new parents each year have a better 
opportunity to donate their newborn's cord blood, an important new 
donor bank can be created quickly, conveniently, without pain, and 
without controversy. And it remains my privilege to serve as living 
proof of the promise of cord blood for the adult leukemia community. 
Although we think of it as a children's disease, 90 percent of all 
leukemia cases are diagnosed in middle-aged adults. But regardless of 
age, cord blood is a proven alternative for saving lives that needs 
your support to become more readily available.
    Thank you for the opportunity to share my concerns with you and I 
would be happy to answer questions at the appropriate time.
                                        Stephen R. Sprague,
                                               Cord Blood Crusader.

    Senator Brownback. And thank you. What an encouraging 
story.
    Have you done any public-service announcements? Because 
you've got a natural gift here.
    [Laughter.]
    Mr. Sprague. Oh, thank you, Senator. In a former life, life 
before leukemia, I appeared before lots of committees, but 
never on something about life or death. It was always about all 
the unimportant stuff. So I appreciate this opportunity.
    Senator Brownback. We spend a lot of time on unimportant 
stuff. But we do spend some time on important things, as well. 
And you're sitting next to quite a star.
    Mr. Penn, you've received quite notoriety, I know, already, 
you're quite a remarkable young man. Will you tell us your 
story?

          STATEMENT OF KEONE PENN, SNELLVILLE, GEORGIA

    Mr. Penn. My name is Keone Penn. Two days ago, I turned 17. 
Five years ago, they said I wouldn't live to be 17.
    I was born with sickle-cell anemia. My mother said I was a 
crying baby. She didn't realize I was in pain.
    I had a stroke when I was 5 years old. The teacher called 
my mom from preschool and said that I had been acting funny all 
day. My mother knew the symptoms, because she had seen it with 
my grandparents.
    They had to do a blood exchange of my whole body. I had 
brain damage to the right side of my brain. I couldn't walk or 
talk for a long time. I had to relearn everything.
    Things got worse after that. My life was full of pain 
crises, blood transfusions, and more times in the hospital than 
I can count. I was never able to have a normal life. I couldn't 
play sports, like basketball or football.
    And I had a tube in my chest, and some kids bullied me and 
threatened to hit me in my chest, and I felt like an outsider, 
like I wasn't a normal kid. And it was just hard.
    And I was suicidal then. Every day I'd go to school and 
people would pick on me. I couldn't take it any more. One day, 
I came home from school with a sad look on my face. My sister 
got home after me, and my mom had went to work. I went in my 
room, sat on my bed, and cried. I had suicide on my mind.
    Then I thought about my family, how they would miss me. I 
thought about my mom, my sister, my aunt, and my cousin, how 
they would cry if I, you know, would die. I held my head up and 
dried my eyes. My mother always said we have to do what we have 
to do, and that you have to deal with the life you are given.
    The year before I had the transplant, I was in the hospital 
13 times. I knew everybody in the hospital and had been in just 
about every room on the floor.
    Then my mom, one day when I was in the hospital, she came 
into the room, looking all depressed, because I had had a pain 
crisis. And she was really sad, and she just looked at me, and 
said, ``Keone, they want to try something. They want to do a 
cord-blood transplant. They said if you don't do it in the next 
5 years, you're going to have another stroke that could be 
fatal. And this is experimental, and, you know, we have to work 
together on this.'' And she said, ``So what do you think? Do 
you want to do it?'' And I was thinking I'd rather go out 
fighting than just wait and know you're going to die, you know, 
because nobody wants to die. So I said yes, and we did the 
cord-blood transplant.
    My cord-blood transplant wasn't easy, but I thank God I'm 
still here. I had a lot of problems, like graft versus host 
disease, which is a rejection of the new cells.
    I thought the coolest part about my transplant was that my 
blood type has changed from O to B.
    [Laughter.]
    Mr. Penn. I missed a lot of school, and I had to do a 
couple of years of home-schooling. But I still made all A's and 
B's. I made B's this year.
    [Laughter.]
    Mr. Penn. Next year, I will graduate from high school. My 
family will be so proud to see me graduate, because they 
thought I wouldn't live long enough to graduate. Before I had 
my transplant, they said I wouldn't live another 5 years.
    My graduation will mark a big victory in my life. I want to 
become a chef. I plan to go to a good culinary arts school in 
Georgia. I cook for my family all the time. I think I'm pretty 
good at it.
    [Laughter.]
    Mr. Penn. My life, with sickle cell, was very rough. I have 
been through more things than most grownups can only imagine. 
But sickle cell is a part of my past. One year after my 
transplant, they pronounced me cured of sickle-cell anemia. 
Cord blood saved my life. Now I can look forward to a brighter 
future.
    Thank you.
    [The prepared statement of Mr. Penn follows:]

         Prepared Statement of Keone Penn, Snellville, Georgia

    My name is Keone Penn. Two days ago, I turned 17 years old. Five 
years ago, they said I wouldn't live to be 17. They said I'd be dead 
within 5 years. I was born with sickle cell anemia. Sickle cell is a 
very bad disease. I had a stroke when I was 5 years old. Things got 
even worse after that. My life has been full of pain crises, blood 
transfusions every two weeks, and more times in the hospital than I can 
count. The year before I had my stem cell transplant, I was in the 
hospital 13 times. I never was able to have a normal life. My stem cell 
transplant was not easy, but I thank God that I'm still here. I will 
graduate from high school this year. I want to become a chef because I 
love to cook. I think I'm pretty good at it. Sickle cell is now a part 
of my past. One year after my transplant, I was pronounced cured. Stem 
cells saved my life. Thank you.

    Senator Brownback. Thank you.
    Those are very impressive statements and very impressive 
comments.
    Mr. Barsh and Mr. Sprague, I'm curious--and you may want to 
involve any of the researchers that can comment on this, as 
well.
    Senator Brownback. You have commented that timing is 
critical determining the need for cord blood. Every minute, 
every day counts on this.
    Mr. Barsh, you were right on top of this at an early phase. 
How do we catch these earlier? What's your advice on how we 
catch these to be able to intercept as fast as possible, number 
one? And I want to ask you, as well, is this the sort of thing 
if you catch it right at birth, you're likelihood of success is 
far greater than if it drags on for a period of time?
    Mr. Barsh. Senator, they're all excellent questions, and 
thank you for asking me, and I'll just comment.
    One way that these types--or many, but not all--of the 
neurodegenerative diseases can be caught is by better prenatal 
testing--or testing, immediately after birth, like PKU testing, 
which is mandated today for every baby born. It's done on a 
state-by-state basis, but not a Federal basis. In about a year, 
there's going to be a test for adrenoleukodystrophy, so it 
could be screened and caught earlier.
    Ours was caught in a very unfortunate circumstance, where 
one of Spencer's oldest cousins is in a persistent vegetative 
state from ALD today. There were three boys in our family that 
had it, because it's X-linked and gets passed down. So Oliver 
was the martyr and won't be able to recover, but he saved two 
other kids in the family.
    But better testing----
    Senator Brownback. I'm sorry----
    Mr. Barsh. Yes?
    Senator Brownback.--Mr. Barsh----
    Mr. Barsh. Yes.
    Senator Brownback.--let me back up on this a bit. What time 
was it caught in him?
    Mr. Barsh. He was about, I would say, seven or 8 years old, 
and he had been seeing physicians for about four or 5 years for 
some type of problem that had been misdiagnosed as everything--
ADD, ADHD, Asperger's Syndrome--which is very common with our 
type of disease.
    So I'd say I think the other thing that Congress could do 
would be to pass legislation, from a healthcare point of view--
and I'll just talk to one narrow area, which is children. 
Children that display some type of mental delay, or some type 
of symptom that wants to be diagnosed as ADD or ADHD--a very 
simple, painless MRI can be performed on their brains just to 
make sure it's nothing else.
    In certain countries in Europe today--I believe, in 
France--it's actually mandated. If a child has developmental 
delay, they do an MRI to check. That's how you could catch a 
lot of these diseases, because they slip through.
    A typical pediatrician, our pediatrician, that has Spencer 
as a patient, that had ALD, she'll never see another child in 
her career with the disease. Around one in 10-13,000 kids has 
ALD. And it's so rare a single pediatrician would see it.
    So I think better education for physicians, and laws 
mandating that children that have some type of developmental 
delay be screened. Again, screening right after birth for a 
number of these diseases--you know, West Virginia screens for 
two diseases. Pennsylvania screens for about 26. It differs 
state by state.
    Senator Brownback. Can you screen before birth for ALD?
    Mr. Barsh. Yes, you can. You can screen at CVS testing. You 
can screen during amniocentesis. It's not typically screened 
today, because, the genetic testing labs will tell you, ``You 
can't screen for everything. Otherwise, we'll be screening for 
forever.'' So they do it--if there's a family history, they can 
absolutely screen for it today.
    Senator Brownback. Are there treatments, even before birth? 
Are there in-utero treatments?
    Mr. Barsh. Not really. One of the things I believe some 
researchers are looking toward the future of doing in-utero 
cord-blood transplants, which, to me, is staggeringly 
interesting. But, yes, you could absolutely, if you knew.
    And that technology--it's not there today, I believe. And I 
think Dr. Kurtzberg could address that specifically. But----
    Senator Brownback. Dr. Kurtzberg, would you mind sitting up 
here? I know this isn't the way we normally proceed. And if any 
of the other researchers want to pitch in, but I really would 
like to get at this point, about at what age and stage can cord 
blood can be the most successful.
    Dr. Kurtzberg. Well, newborn screening could be available 
for most of these diseases. But it is not available on a 
routine basis or a mandatory basis. And even when parents 
request it, most of the time their pediatricians think it's not 
indicated. But if it was part of the standard newborn screening 
panels, it would be wonderful.
    And what would be needed for that is, you know, an RFP to 
invite proposals to develop simple technology on dot-blot 
testing for newborn screening for these metabolic diseases.
    Senator Brownback. Which do not exist today.
    Dr. Kurtzberg. Well, I mean, there are researchers working 
on the technology. It does exist, but it is not implemented in 
the United States, and it should be. Because all of these 
diseases would fare better if they were treated early in life. 
And regardless of what disease you're treating, children do 
better with transplant earlier in life. We don't have to use 
quite as much chemotherapy. They tolerate the procedure better.
    I don't know if you remember, but our young Krabbe kids 
have 100 percent survival because they're healthier. And even 
though they have that bad disease, the rest of them can 
tolerate the therapy and the medicines easier.
    Senator Brownback. What about in-utero diagnosis and 
treatment?
    Dr. Kurtzberg. Well, yes, there are--diagnosis is certainly 
possible. Parents can also be screened to see if they're 
carriers so they know whether or not they would be possibly 
conceiving a child with the disease. There's something called 
pre-implantation diagnosis, which allows selection of a healthy 
embryo. More commonly, people use CVS or amnio, as Steve 
mentioned, to make an in-utero diagnosis.
    In-utero treatment is more complicated. There have been 
transplants tried in the second or third trimester. You 
obviously can't give a fetus chemotherapy. And most of the time 
they're either rejected because the fetus has enough of an 
immune system to not retain the cells; or there are too many 
cells, and the balances are off.
    What probably would work and has been demonstrated in 
animals is that if you did the transplant in the first 
trimester of pregnancy, which would require diagnosis by CVS, 
those cells would probably be tolerated by the fetus because 
it's in a state called a pre-immune state. But no one knows 
that for sure, and a lot more research has to be done to prove 
that. But, theoretically, and in animals, that looks like the 
way to go.
    Senator Brownback. We're looking to set up a hearing on in-
utero treatments, because there's a burgeoning field of 
treatments that--some spina bifida is being successfully 
treated in utero--that are really, really fantastic.
    Dr. Kurtzberg. Well, you would a 10- to 12-week fetus and 
inject cord-blood cells into the belly, or the forming abdomen, 
and those cells would induce tolerance so that, later, they 
could be boosted, after birth, without chemo.
    Senator Brownback. Well, that's interesting.
    Dr. Kurtzberg. But you have to know that the baby has the 
diagnosis, and that, again, has been done in animals, but not 
in people.
    Senator Brownback. This procedure you've described has not 
been performed on people.
    Dr. Kurtzberg. No.
    Senator Brownback. But it has been successful in an animal 
model.
    Dr. Kurtzberg. Correct. And there are people talking about 
implementing it in people. But it takes a lot of things to come 
together. I mean, you have to know there's a risk, someone has 
to have a CBS, and then you have to be able to mobilize the 
donor in a week, which you could do with cord blood.
    Senator Brownback. Mr. Sprague, in your treatment and the 
situation you're in, what advice do you give to patient groups? 
You said you speak quite a bit. Is it early screening? Do we 
have to do more in the cord-blood field? Is it to look at the 
option of cord blood, which a lot of people don't know about, 
instead of bone marrow?
    Mr. Sprague. Early detection is kind of interesting for 
blood cancers. There are few symptoms. Usually the diagnosis is 
a total shock, because you don't feel like you have cancer. You 
know you have a blood cancer, by a simple blood test. So one of 
the easiest things for everybody to do is just check your oil 
once in awhile. Get a blood test and make sure that everything 
is OK. Some of us do that religiously; some of us seldom do it.
    Once you've been diagnosed with a blood cancer, while 
chemotherapy will only keep the disease manageable--and, in 
some cases, for many, many years--it's just known that the only 
cure--and leukemia is one of the few cancers that people can 
look you in the eye and tell you you're cured--is a successful 
stem cell transplant. The problem, as I said earlier, is if you 
can't find a stem cell match, then you have no cure, and you 
sit home, and you wait to die.
    When you compare having to go through a marrow search with 
the ability to find a cord-blood match sitting on the shelf 
somewhere--already typed, already collected, already screened, 
already matched to your particular type--I mean, that's going 
to save you months, sometimes more than months. And usually 
when patients decide to go to transplant, they're in the 
serious stages of the disease.
    When you're feeling pretty good and you've been early 
diagnosed with the leukemia, transplant is something you think 
is way down the line. So if you can improve the time to find a 
match by having an inventory of stored cord blood, as opposed 
to a bunch of people who have, out of the goodness of their 
heart, said, ``I'll be a donor if I match somebody and if you 
can find me when the time comes to get my marrow,'' that's 
going to save an awful lot of lives of blood cancer patients 
who are in distress to the point where if something doesn't 
happen quick, then they're going to die.
    Senator Brownback. Mr. Penn, you've got quite a remarkable 
story that you've put forward in being cured of sickle cell 
anemia. What's your advice to others that have suffered under 
the same disease that you've gone through? Is it to really seek 
to find cord blood that can match and that can do this and at 
earlier ages?
    Mr. Penn. Yes. Because, I mean, I can only imagine how hard 
it is on other people. And I'm just one kid with sickle cell. I 
mean, you could walk up to anybody today, and they could have 
sickle cell. They probably wouldn't tell you, but--and there's 
probably a lot of people in the world who have sickle cell and 
who are looking for a cure. And this could really help them.
    And if I could help them, I would like to. I mean, I'd do 
all I can to make sure nobody goes through what I went through.
    Senator Brownback. How many years ago did you go through 
the procedure?
    Mr. Penn. Five years ago.
    Senator Brownback. Five years ago.
    Mr. Penn. Yes, it'll be 5 years on December 11.
    Senator Brownback. And it was very difficult for you at 
that time, going through the chemotherapy and----
    Mr. Penn. Yes.
    Senator Brownback. Now, if this had been caught earlier and 
tried earlier, would that have been easier?
    Mr. Penn. Probably. Because your body's more healthy when 
you're a baby, so your body's able to accept the chemotherapy 
when you have to do the chemo. And since my body had aged, my 
body really didn't accept it that much. The cells either--since 
the cells had been in my body so long, they were fighting it 
off. That's probably why I got graft versus host disease, too.
    Senator Brownback. Dr. Kurtzberg, is this one that could 
have been--if you know and have a family history--diagnosed in 
utero, the procedure started that you had described?
    Dr. Kurtzberg. Certainly with the appropriate research on 
the procedure. But most states have screening programs for 
sickle cell in newborns, so it is pretty universally diagnosed 
at birth now. And medical therapy, like antibiotics and extra 
visits to the pediatrician and education of parents about 
crises, et cetera, is started in the first year of life. If 
those babies were transplanted in the first year of life, one, 
they would tolerate it better, they would have a higher 
survival. They wouldn't have damage to their tissues that 
sickle cell, itself, causes or the transfusions cause. So the 
whole process is easier. And, hearing Keone's story, how he had 
to miss school and how, socially, he had issues because he was 
sick and he couldn't attend school normally, are avoided when 
you transplant a newborn. Because by the time they recover, 
they're two or one and a half, and they're at a point where 
they really haven't missed out on school or other social 
developmental things that older children need to have.
    Senator Brownback. Is this being done regularly now in 
sickle cell diagnosis? Is the cord blood?
    Dr. Kurtzberg. The diagnosis is regular. Cord blood 
transplant is not regular.
    Senator Brownback. Why not?
    Dr. Kurtzberg. Because, I think, the hematology community 
worries about the mortality risks. And there is a natural study 
of sickle cell disease, which is ongoing, which shows that not 
all patients will have a severe course. Some do and some don't. 
And there have yet to be predictors identified that say which 
of the patients will be having strokes as children, et cetera. 
And so, because of that, there's been a reluctance to recommend 
that all children with the disease are treated.
    And thalassemia, which is another hemoglobin problem where 
children don't make red cells effectively at all and are 
dependent on transfusions from the age of about five or 6 
months, there's more acceptance to doing it in infancy because 
it's known that that disease, because if iron buildup, will be 
fatal in usually the second or third decade of life.
    Senator Brownback. Now, in Keone's case, where at age five, 
had a stroke, he would be clearly be somebody that you would 
say we need to do the cord blood, with the knowledge that we 
have now.
    Dr. Kurtzberg. Right. Correct. And that is starting to 
happen. Yes.
    Senator Brownback. Good.
    Dr. Kurtzberg. But, you know, just as a point, in some 
states, Medicaid won't cover HLA typing for a sickle cell 
patient. That's the tissue typing that you need to have to 
know: Do you have a donor in your family or do you need to look 
for an unrelated donor? So that's not even a universal health 
care benefit, and it certainly should be.
    The other thing I wanted to say about genetic diseases is 
that parents are a huge resource, and they are huge advocates 
for their children. And as much as it's important to educate 
pediatricians, of which I am one, I think that the parents can 
be empowered, in large part, to do a lot to get their children 
screened and to use tests that might be made available to them. 
And that parental education about some of these diseases would 
help make things happen. And with the Internet, there's a huge 
tool now to bring about some programs that would be beneficial 
to all, and not that expensive to implement.
    Senator Brownback. Ms. Penn, do you have anything to tell 
us about your experience with this?
    Ms. Penn. Well, there's quite a few things I could actually 
tell you. In Keone's experience, his life has been pretty 
difficult with sickle cell. And, like he said earlier, if 
there's a opportunity or a chance that another child doesn't 
have to go through things that my child has been through, 
that's a gift from God, and hopefully, this will bring about 
some change.
    Senator Brownback. Yes. Hopefully, it will.
    Thank you very much. This has been a very encouraging 
group, all of you. You've been very thoughtful.
    I hope all of you do public service announcements, get the 
word out. I hope there's lots of comments and quotes that are 
attributed to you, because I think this is the sort of thing we 
need to build a lot of knowledge and exposure to. This is a 
truly remarkable set of developments that--areas we hadn't 
thought we had much hope--and a whole new alternative to be 
able to go with.
    I'm very heartened by this and by your comments. That's 
another area for us to look at, is the Medicaid coverage on the 
sickle cell blood typing.
    Dr. Kurtzberg. HLA typing. Tissue typing or HLA typing.
    Senator Brownback. OK.
    Well, thank you. God bless you all for coming forward. 
Thanks for being here. And hopefully we'll make some good 
progress in this area.
    The hearing is adjourned.
    [Whereupon, at 4:33 p.m., the hearing was adjourned.]


                            A P P E N D I X

       Testimony of the American Academy of Physician Assistants

    On behalf of the more than 46,000 clinically practicing physician 
assistants in the United States, the American Academy of Physician 
Assistants is pleased to submit comments in response to the 
Subcommittee's June 12 Hearing on Advances in Adult and Non-Embryonic 
Stem Cell Research.
    The Academy applauds the wonderful advances in adult and non-
embryonic stem cell research that were highlighted in the 
Subcommittee's hearing of June 12. The field of regenerative medicine 
does indeed offer great hope to individuals who are suffering from 
disease. However, to fully realize the enormous potential benefits in 
medical research and human healing, the AAPA believes that the use of 
human embryonic stem cell research, including the use of nuclear 
transplantation techniques (also known as non-reproductive, research or 
therapeutic cloning), must also be fully supported. The promises of 
human embryonic stem cell research are, through its eventual 
application in the hospital and office, to ease human suffering, save 
lives and harness fundamentally novel avenues for patient care.

Physician Assistants (PAs)
    Physician assistants are legally regulated in all states to 
practice medicine as delegated by and with the supervision of a 
physician. Physicians may delegate to PAs those medical duties that are 
within the physician's scope of practice and the PA's training and 
experience, and are allowed by law. A physician assistant provides 
health care services that were traditionally only performed by a 
physician. Forty-seven states, the District of Columbia, and Guam 
authorize physicians to delegate prescriptive privileges to the PAs 
they supervise. An estimated 170 million patient visits were made to 
PAs and approximately 213 million medications were prescribed or 
recommended by PAs in 2001.
    PAs work in virtually every area of medicine and surgery and are 
covered providers of physician services through Medicare, Tri-Care, and 
most private insurance plans. Additionally, PAs are employed by the 
Federal Government to provide medical care, including the Department of 
Veterans Affairs, the Department of Defense, and the Public and Indian 
Health Services.

American Academy of Physician Assistants (AAPA)
    The American Academy of Physician Assistants was founded in 1968 
and is the only national organization representing physician assistants 
(PAs) in all medical specialties. The Academy educates the general 
public about the PA profession, assures competency of PAs through 
active involvement in the development of educational curricula and 
accreditation of PA programs, provides continuing education, and 
conducts PA-related research. The mission of the Academy is to promote 
quality, cost-effective health care, and the professional and personal 
growth of physician assistants.

AAPA Policy on Stem Cell Research
    The AAPA's policy on stem cell research is based on the desire to 
promote the intense, vigorous, and responsible scientific research that 
will be necessary to realize the potential medical benefits of using 
stem cells to treat disease and repair tissue damaged by disease or 
trauma. The research holds tremendous promise for the development of 
new treatments for a wide range of serious illness and injury, such as 
Parkinson's disease, Alzheimer's disease, cancer, diabetes, heart 
disease, arthritis, neurodegenerative and immunodeficiency diseases, 
and spinal cord injury.
    The AAPA policy on stem cell research was adopted by the Academy's 
House of Delegates in 2002 and 2003. Four principles are core to the 
Academy's collective policy--

    Federal funding must be used to support embryonic stem cell 
        research.

    Productive research requires a larger source of stem cell 
        lines than those in existence on August 9, 2001, necessitating 
        the isolation of new embryonic cell lines.

    The cloning of human beings for the purpose of reproduction 
        must be prohibited.

    The use of nuclear transplantation techniques should be 
        promoted as a desirable means to create embryonic stem cells 
        for research purposes.

    The AAPA believes the Federal government is the single, best source 
for the large and sustained financial investment needed to move the 
research forward. The Federal government must play an important role in 
providing public review, approval, and monitoring of the research, as 
well as insuring the scientific and ethical appropriateness of the 
research.
    Concerns regarding the age, quality, ownership, and racial and 
ethnic variability of the cell lines available on or before August 9, 
2001 led the AAPA to support the isolation of new embryonic cell lines. 
Questions about whether appropriate informed consent from the donors of 
embryos that had been used to develop the earlier cell lines further 
substantiated the need to support the isolation of new embryonic cell 
lines.
    In developing its support for embryonic stem cell research, the 
Academy addressed difficult ethical considerations, which led to policy 
being adopted to safeguard the use of donated embryos, including the 
appropriate use of excess, abandoned, or non-transferable frozen 
embryos currently stored at in vitro fertilization clinics.
    In 2003, the AAPA affirmed and strengthened its opposition to the 
inappropriate use of human embryos by adopting policy to support a 
legally enforceable ban on the cloning of human beings for the purpose 
of reproduction.
    The creation of stem cells by nuclear transplantation is supported 
as an ethically responsible means of isolating new embryonic stem cell 
lines, because the procedure does not involve implantation of a 
blastocyst in a uterus, nor is it intended to lead to the birth of a 
cloned human being. The stem cells that are produced are unspecialized 
cells that can renew themselves indefinitely and, under the right 
conditions, develop into more mature cells with specialized functions. 
Furthermore, the cells are created with the express permission of the 
donor and the express understanding that the tissue will be used for 
stem cell derivation only, not for implantation and reproduction.
    The AAPA believes that stem cell research and nuclear 
transplantation hold tremendous potential to ease human suffering 
through advanced therapies. The Academy applauds the Subcommittee's use 
of the June 12 hearing to showcase the remarkable advances in medicine 
that have been made in the fields of adult and non-embryonic stem cell 
research. However, the Academy also urges the Subcommittee to consider 
the appropriate and responsible use of embryonic stem cell research. No 
other current avenue of medical research holds the promise of human 
embryonic stem cells.
    Thank you for the opportunity to submit the comments of the 
American Academy of Physician Assistants to the Hearing Record.

                                  
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