[Senate Hearing 105-939]
[From the U.S. Government Publishing Office]


                                                        S. Hrg. 105-939
 
                           STEM CELL RESEARCH

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

                                HEARINGS

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                       ONE HUNDRED FIFTH CONGRESS

                             SECOND SESSION

                               __________

                            SPECIAL HEARING

                               __________

                    DECEMBER 2, 1998--WASHINGTON, DC
                    JANUARY 12, 1999--WASHINGTON, DC
                    JANUARY 26, 1999--WASHINGTON, DC

                               __________

         Printed for the use of the Committee on Appropriations


 Available via the World Wide Web: http://www.access.gpo.gov/congress/
                                 senate

                                 ______

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                      COMMITTEE ON APPROPRIATIONS

                     TED STEVENS, Alaska, Chairman
THAD COCHRAN, Mississippi            ROBERT C. BYRD, West Virginia
ARLEN SPECTER, Pennsylvania          DANIEL K. INOUYE, Hawaii
PETE V. DOMENICI, New Mexico         ERNEST F. HOLLINGS, South Carolina
CHRISTOPHER S. BOND, Missouri        PATRICK J. LEAHY, Vermont
SLADE GORTON, Washington             DALE BUMPERS, Arkansas
MITCH McCONNELL, Kentucky            FRANK R. LAUTENBERG, New Jersey
CONRAD BURNS, Montana                TOM HARKIN, Iowa
RICHARD C. SHELBY, Alabama           BARBARA A. MIKULSKI, Maryland
JUDD GREGG, New Hampshire            HARRY REID, Nevada
ROBERT F. BENNETT, Utah              HERB KOHL, Wisconsin
BEN NIGHTHORSE CAMPBELL, Colorado    PATTY MURRAY, Washington
LARRY CRAIG, Idaho                   BYRON DORGAN, North Dakota
LAUCH FAIRCLOTH, North Carolina      BARBARA BOXER, California
KAY BAILEY HUTCHISON, Texas
                   Steven J. Cortese, Staff Director
                 Lisa Sutherland, Deputy Staff Director
               James H. English, Minority Staff Director
                                 ------                                

 Subcommittee on Departments of Labor, Health and Human Services, and 
                    Education, and Related Agencies

                 ARLEN SPECTER, Pennsylvania, Chairman
THAD COCHRAN, Mississippi            TOM HARKIN, Iowa
SLADE GORTON, Washington             ERNEST F. HOLLINGS, South Carolina
CHRISTOPHER S. BOND, Missouri        DANIEL K. INOUYE, Hawaii
JUDD GREGG, New Hampshire            DALE BUMPERS, Arkansas
LAUCH FAIRCLOTH, North Carolina      HARRY REID, Nevada
LARRY E. CRAIG, Idaho                HERB KOHL, Wisconsin
KAY BAILEY HUTCHISON, Texas          PATTY MURRAY, Washington
TED STEVENS, Alaska                  ROBERT C. BYRD, West Virginia
  (Ex officio)                         (Ex officio)
                      Majority Professional Staff
                            Bettilou Taylor
                             Mary Dietrich

                      Minority Professional Staff
                              Marsha Simon

                         Administrative Support
                   Jim Sourwine and Jennifer Stiefel



                            C O N T E N T S

                              ----------                              
                                                                   Page

                      Wednesday, December 2, 1998

Statement of Harold Varmus, M.D., Director, National Institutes 
  of Health, Department of Health and Human Services.............     1
Opening remarks of Senator Arlen Specter.........................     1
Opening statement of Senator Tom Harkin..........................     2
Prepared statement of Dr. Harold Varmus..........................     8
Statement of John D. Gearhart, Ph.D., professor of gynecology and 
  obstetrics, Johns Hopkins University School of Medicine........    11
    Prepared statement...........................................    12
Statement of James Thomson, Ph.D., associate research animal 
  veterinarian, Wisconsin Regional Primate Research Center.......    14
    Prepared statement...........................................    16
Statement of Michael West, Ph.D., president and chief executive 
  officer, Advanced Cell Technology..............................    19
    Prepared statement...........................................    20
Curing disease...................................................    26
Parkinson's disease..............................................    27
Use of embryos...................................................    28
Federal ban on research on human embryos.........................    28
Treating age-related degenerative diseases.......................    31
Cloning..........................................................    31
Parkinson's disease..............................................    32
Diabetes.........................................................    33
Statement of Arthur L. Caplan, Ph.D., director, Center for 
  Bioethics, University of Pennsylvania..........................    35
    Prepared statement...........................................    37
Statement of Richard M. Doerflinger, associate director for 
  policy development, secretariat for pro-life activities, 
  National Conference of Catholic Bishops........................    42
    Prepared statement...........................................    44
Statement of Thomas B. Okarma, Ph.D., M.D., vice president of 
  research and development, Geron Corp...........................    51
    Prepared statement...........................................    52
Statement of Eric Meslin, Ph.D., executive director, National 
  Bioethics Advisory Commission..................................    66
    Prepared statement...........................................    67
Fetus destruction................................................    68
Prepared statement of Daniel Perry, on behalf of the Alliance for 
  Aging Research.................................................    76

                       Tuesday, January 12, 1999

Statement of Maria Freire, Ph.D., Director, Office of Technology 
  Transfer, National Institutes of Health, Department of Health 
  and Human Services.............................................    79
Opening remarks of Senator Arlen Specter.........................    79
Technology transfer legislation..................................    80
Research tools...................................................    81
Prepared statement of Maria Freire...............................    82
Statement of Q. Todd Dickinson, J.D., Acting Assistant Secretary 
  of Commerce, and Acting Commissioner of Patents and Trademarks, 
  Department of Commerce.........................................    85
    Prepared statement...........................................    87
Remarks of Senator Tom Harkin....................................    91
    Prepared statement...........................................    93
Time constraints.................................................    94
Statement of Lawrence Goldstein, Ph.D., professor of 
  pharmacology, Division of Cellular and Molecular Medicine, 
  University of California at San Diego..........................    95
    Prepared statement...........................................    97
Statement of Doug Melton, Ph.D., representing the Juvenile 
  Diabetes Association, Harvard University.......................    98
    Prepared statement...........................................   100
Statement of Richard Pikunis, J.D., Parkinson's patient, Marlton, 
  NJ.............................................................   102
Prepared statement of the Biotechnology Industry Organization, 
  [BIO]..........................................................   104
Obtaining by ethical means.......................................   108
Patentability of research tools..................................   110
Bayh-Dole Act....................................................   110
University of Wisconsin research.................................   113
Bayh-Dole........................................................   114

                       Tuesday, January 26, 1999

Statement of Harold Varmus, M.D., Director, National Institutes 
  of Health, Department of Health and Human Services.............   117
Opening remarks of Senator Arlen Specter.........................   117
Prepared Statement of Dr. Harold Varmus..........................   121
Statement of Harriet Rabb, J.D., General Counsel, Department of 
  Health and Human Services......................................   123
Remarks of Senator Tom Harkin....................................   123
Statement of Eric M. Meslin, Ph.D., executive director, National 
  Bioethics Advisory Commission..................................   128
    Prepared statement...........................................   130
Statement of Richard M. Doerflinger, associate director for 
  policy development, secretariat for prolife activities, 
  National Conference of Catholic Bishops........................   131
    Prepared statement...........................................   134
Cells are units of organisms--organisms are units of life........   142
  


                           STEM CELL RESEARCH

                              ----------                              


                      WEDNESDAY, DECEMBER 2, 1998

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:34 a.m., in room SD-192, Dirksen 
Senate Office Building, Hon. Arlen Specter (chairman) 
presiding.
    Present: Senators Specter and Harkin.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF HAROLD VARMUS, M.D., DIRECTOR

                   opening remarks of senator specter

    Senator Specter. The Subcommittee on Labor, Health and 
Human Services, and Education will now proceed.
    Senator Harkin and I discussed our agenda for the year 
several weeks ago and jointly decided that our initial hearing 
ought to be on the highly charged, very important subject about 
the use of human embryos and fetal tissue for medical research 
and have accordingly scheduled this hearing today.
    Before proceeding to the hearing, just a word or two about 
reports of my own consideration for changing chairmanships of 
subcommittees. I will be remaining as chairman of the 
Subcommittee on Labor, Health and Human Services, and 
Education. I had given some brief consideration to a change. I 
was surprised, flattered, to hear so many people say that I 
should stay.
    These rumors have a way of appearing in print and sort of 
out of control. But to put that matter to rest, I shall be 
remaining as chairman of this subcommittee.
    The subject matter on our hearing today arises from a 
provision of the legislation reported out by this subcommittee 
last year, which limits the use of Federal funds for research 
on human embryos. That is an issue which has come into sharp 
focus with very dramatic recent medical developments, 
warranting a closer analysis or perhaps a reanalysis of that 
question.
    There is a curious dichotomy, really an inconsistency or an 
arguable inconsistency, when Federal funds may be used on 
research on fetal tissue, but not on human embryos. While there 
are very substantial differences, the question is raised as to 
whether that is a consistent policy.
    The recent advances have shown that the stem cells have 
potential to grow into any kind of bodily tissue and have, at 
least reportedly, enormous potential on a wide variety of very 
serious ailments--heart disease, diabetes, Alzheimer's, cancer, 
spinal cord. We will get into a full range as we hear from our 
expert witnesses today.
    The problems with embryos are unique because the embryo has 
the potential to create a new person under some circumstances, 
and we shall explore that. There has been consideration raised 
about the use of discarded embryos where couples using 
fertility treatment discard embryos, another very complex and 
controversial and very highly charged subject.
    The discussion which we will be initiating today, or 
carrying forward today, is one which will challenge ethicists 
and theologians as well as Senators and members of the House. 
The collateral question arises as to whether these procedures 
may be patented. Some applications have already been made for 
patents. So there are many, many questions which are raised on 
this very, very important subject because of the potential to 
treat illnesses of enormous importance and whether this is an 
appropriate procedure.
    That in a very brief statement, is an outline of some of 
our parameters which we will expand during the course of 
today's hearing and beyond. I now turn to my distinguished 
colleague, the ranking member, Senator Harkin.


                opening statement of senator tom harkin


    Senator Harkin. Mr. Chairman, thank you very much for your 
leadership of this committee. Thank you for holding this 
important hearing to air the ethical and scientific issues 
involved in stem cell research. I am pleased to have this 
opportunity to hear directly from Dr. Varmus, our lead-off 
witness, the distinguished scientists who have conducted this 
ground-breaking research, as well as from the ethicists who 
have examined the moral implications.
    While the press has highlighted the exciting potential 
benefits of Dr. Thomson and Dr. Gearhart's work, they have 
spent much of their time documenting the controversy 
surrounding their accomplishments. They have focused on the 
Federal ban on human embryos research, the ethical implications 
of advanced cell technologies research with human and bovine 
cells, the President's request to the National Bioethics 
Advisory Commission, and the scientific furor over the release 
of ACT's unpublished research to the New York Times.
    All of these issues deserve a full debate, and again I 
thank you, Mr. Chairman, for bringing us together today. I also 
want to thank you for continuing on and staying as chairman of 
this subcommittee. I had heard these rumors and I thought if 
they got very serious I was going to threaten you with great 
bodily harm if you decided to leave. So I am grateful that you 
did stay.
    Senator Specter. That kind of bodily harm might not be 
cured by stem cells, either. [Laughter.]
    Senator Harkin. They would have to hurry up the research.
    I want to thank Dr. West for his commitment to a public 
discussion of the ethical implications of stem cells research 
and to commend Doctors Thomson and Gearhart for their 
groundbreaking accomplishments. From enabling the development 
of cell and tissue transplantation to improving and 
accelerating pharmaceutical research and development, to 
increasing our understanding of human development and cancer 
biology, the potential benefits of this work are awe-inspiring. 
The cell lines they have isolated and kept alive could reduce 
the demand for organ donors and pave the way for many life-
saving therapies.
    They could help pharmaceutical companies improve the 
testing of their products by providing an unlimited quantity of 
normal human cells of any tissue. Therefore, rather than going 
directly from animal testing to human testing, they could test 
these new drugs for benefits and adverse effects on normal 
human tissue.
    And undoubtedly, a long-term benefit if their work will be 
to enhance our understanding of human development, as 
scientists may now be able to produce cells at specific stages 
of human development that have previously been inaccessible to 
research.
    But all of these benefits could be delayed or even denied 
to patients without a healthy partnership between the private 
sector and the Federal Government. As many of you know, Senator 
Specter and I are strong supporters of this partnership, and we 
were pleased to be able to provide an historic increase for NIH 
in this year's budget and will continue to work to double the 
NIH budget in the next few years.
    Now, while the market interest in stem cell technology is 
strong and private companies will continue to fund the 
research, the Government has an important role to play in 
supporting the basic and applied science that underpins these 
technologies. The problem is that early basic science is always 
going to be underfunded by the private sector because this type 
of research does not get products to the market quickly enough.
    The only way to ensure that this research is conducted is 
to allow NIH to support it. But unfortunately, as the American 
Society for Cell Biology writes in a recent letter, the ban on 
human embryo research ``has the effect of excluding the 
majority of the Nation's most prominent researchers who are 
supported by the NIH and limits the development of new 
therapies.''
    The key question that I hope will be addressed today is 
whether under current law scientists can use Dr. Thomson's stem 
cells for federally funded research. These stem cells do not 
have the capacity to become a human being and, therefore, it is 
my opinion, based upon a lot of study of this, that they do not 
fall under the ban on human embryo research.
    I know that NIH has asked the general counsel at the 
Department to examine the law and make a determination. It is 
my hope that this research will be allowed to go forward.
    I would like to point out that Federal support is critical 
to ensure that stem cell research using human embryos is 
monitored and that consistent, up to date ethical guidelines 
are followed. The research conducted by the distinguished 
scientists sitting before us today holds such hope and such 
potential for millions of people around the world who are sick 
and in pain that I believe it is morally wrong for us to 
prevent or delay our world-class scientists from building on 
this progress.
    However, I think it is right and proper for us as 
policymakers to consider the ethical implications and demand 
that consistent, up to date ethical and scientific guidelines 
are established and followed.
    We reach, I think, in the final analysis, the age-old 
question: What are the limits of human knowledge? I have 
responded consistently that I do not believe there are any 
limits to human knowledge. There are ethical limits that 
society may place on the use of that human knowledge.
    But to limit this kind of research and to limit this kind 
of expansion of human knowledge I believe in the final analysis 
is really unhuman. As long as the research is conducted in an 
ethically validated manner, it should be allowed to go forward 
and it should receive Federal support.
    Thank you, Mr. Chairman.
    Senator Specter. Thank you very much, Senator Harkin.
    In accordance with our regular practice, the 5-minute rule 
will apply for opening statements by each witness. There will 
be substantial time for questions and answers to elaborate upon 
positions taken.


                 summary statement of dr. harold varmus


    Senator Specter. Our lead witness is the distinguished 
Director of the National Institutes of Health, Dr. Harold 
Varmus, who has been at the job since November 1993, passing 
the 5-year mark. At the University of California at San 
Francisco he earned the Nobel Prize for his work on the 
causative link between certain genes and cancer. A graduate of 
Amherst, Harvard, and the Columbia Medical School.
    Again, Dr. Varmus, we welcome you and the floor is yours.
    Dr. Varmus. Mr. Chairman and Senator Harkin: Thank you very 
much.
    First let me express on behalf of the biomedical research 
community and indeed the entire public our pleasure with your 
official decision to remain as chairman of this committee. The 
team you have formed with Senator Harkin here has been truly 
extraordinary and the biomedical research community is 
extremely grateful for your continued support.
    I am also very pleased that you are holding this hearing--
--
    Senator Specter. Did you like the $2 billion increase last 
year? [Laughter.]
    Dr. Varmus. We did, Senator, and we plan to use it well.
    Senator Specter. We have quite a number of chairs where 
staff sits. We have a lot of people standing. You are welcome 
to come up and sit in these green chairs along the sidelines on 
both sides. It should accommodate another 20 people. And you 
may even sit in the first four seats on the Senators' dais, to 
be replaced if you do not have an election certificate or if a 
person arrives with a Senate election certificate. But you are 
welcome to take the seats because of the overflow arrangements.
    Dr. Varmus. Will these arrangements be subtracted from my 
time, Senator?
    Senator Specter. Yes.
    Dr. Varmus. Thank you.
    Senator Specter. We will give you all the time you need, 
Dr. Varmus.
    Dr. Varmus. Thank you. I am very pleased to have a chance 
to join you at this hearing to discuss mainly the recently 
published work by Dr. Jamie Thomson and Dr. John Gearhart that 
has excited both the scientific community and the public. What 
these scientists have done is to establish lines of pluripotent 
human stem cells, cells that grow continuously in culture and 
are capable of forming many different kinds of tissues. This 
work does warrant public attention because of its scientific 
and medical promise and because of the ethical concerns that it 
raises.
    I briefly would like to consider five questions. First, 
what are stem cells, especially pluripotent stem cells? Second, 
what are the potential uses of these stem cells? Third, what 
methods have been used to make pluripotent stem cells? What is 
the ethical status of pluripotent stem cells? And finally and 
briefly, what is the role of NIH in these endeavors?
    I am going to use some charts, Senator, to try to make 
things clear.
    [Chart.]
    Let me begin by pointing out that there are many different 
kinds of stem cells. Stem cells have the general properties of 
being able to renew themselves, as indicated by these arrows, 
to commit themselves to a higher degree of differentiation, a 
higher, more specialized function, and to undergo this level of 
commitment with time. Shortly after fertilization----
    Senator Specter. Dr. Varmus, would you pull one of those 
microphones over to you a little more closely. Thank you.
    Dr. Varmus. Early in the process of the development of a 
human being, after fertilization, cells are completely potent, 
able to develop to give rise to a complete organism. Those 
cells are called totipotent.
    With time, cells become more highly specialized, resulting 
in the formation of cells we call pluripotent, able to make 
many different kinds of cells, but not give rise to an entire 
organism.
    Over the course of development, cells become yet more 
specialized and develop into stem cells that are committed to 
certain specific tissue lineages, like blood or muscle or liver 
or nerve. Such stem cells, that can give rise to specific 
tissues and are committed to those lineages, are found both in 
the course of development in the fetus and in adults, and 
you're no doubt familiar. For example, so-called blood or 
hematopoietic stem cells were recently in the news as a result 
of recent publications indicating that such stem cells can be 
isolated, for example, from cord or placental blood and used as 
a source of treatment in patients who are undergoing bone 
marrow transplantation for cancer.
    Indeed, there is a great deal of research going on with 
these mature forms of stem cells that are committed to specific 
lineages, and much of that research, supported by the NIH and 
by industry, has achieved therapeutic status in the case of 
bone marrow stem cells or blood stem cells, and much work is 
going on with experimental animals to develop other kinds of 
stem cells for various kinds of uses.
    [Chart.]
    But what are the great uses to which these so-called 
pluripotent stem cells might be put? There are a variety of 
venues for such research. First of all, since these cells are 
relatively primitive in their place in the hierarchy, they can 
be used to study the differentiation process that gives rise to 
many different kinds of tissues, and this is going to hopefully 
allow us to understand the origin of birth defects and to 
understand many abnormalities of cell behavior, such as occur 
in cancer, for example.
    That, of course, goes on at the fundamental level. These 
cells may also have many applied uses, for example in 
identifying targets for development of new pharmaceuticals or 
for carrying out simple means to assess the toxicity of 
candidate pharmaceuticals.
    In the realm of therapy, such stem cell lines that are 
pluripotent in character may well be useful for developing 
therapies that supply missing or defective tissues in a wide 
variety of diseases--cells for patients with diabetes, heart 
muscle cells for patients who have impaired cardiac function, 
nerve cells for patients with a variety of neurodegenerative 
diseases, like Parkinson's or Alzheimer's, and, of course, bone 
marrow precursors for patients who have disorders of the blood-
forming system or have been treated for cancers.
    Now, the assumption that all this work can be done is based 
upon the fundamental research necessary to learn how to 
efficiently differentiate pluripotent cells into the respective 
lineages and to overcome the traditional problem of tissue 
rejection due to the immune system.
    How do we get to the point of obtaining such pluripotent 
cells?
    [Chart.]
    Now, there are many ways that this can be done, but let me 
focus on the two that will be the subject of discussions by 
Doctors Gearhart and Thomson. I should mention that these 
methods were developed with NIH funds to study how cells 
develop in experimental animals, particularly the mouse.
    Let me first remind you about the normal sequence of events 
in a simple manner. Development begins, of course, with 
fertilization of an egg by a sperm, shown here as occurs in a 
test tube. That cell undergoes a series of divisions, still 
producing cells that are fully capable of giving rise to an 
embryo. But those cells go through further divisions and 
undergo the first round of specialization, producing this sac-
like structure called a blastocyst, in which the cells that 
will give rise to the mature individual are referred to as 
cells within the inner cell mass.
    The blastocyst then undergoes implantation in the womb and 
eventually may give rise to a fetus, which eventually may give 
rise to a newborn infant.
    In the work conducted by Dr. Thomson, cells were taken from 
the inner cell mass and placed into a petri dish under defined 
conditions that he will describe for you and were then grown in 
culture, producing what are referred to as pluripotent cells 
and proved to be so by a variety of criteria.
    In Dr. Gearhart's work, cells were taken from the gonadal 
region of a fetus which was obtained from a terminated 
pregnancy. These cells from the gonadal region, so-called 
primordial germ cells, were cultured under specialized 
conditions and proven by a variety of tests to be capable of 
giving rise to a variety of tissues--hence this cell line was 
also called pluripotent.
    [Chart.]
    Let me say a few words about the status of such cells. 
There are many issues to be raised about the cells that we're 
talking about today, but one of those questions is whether 
these cells have the ability to give rise to a complete human 
being. The answer to that from a scientific perspective is no.
    I remind you that cells that are developed by 
fertilization, cells early in development, or intact 
blastocysts can, when reintroduced into a womb, give rise to an 
infant, whereas cells removed from the inner cell mass or grown 
as cultured pluripotent stem cells if reintroduced into a 
uterus do not give rise to a new human being. Hence, these 
pluripotent cells cannot be considered organisms and cannot be 
considered to be embryos.
    Now, let me turn at this point to a few additional 
considerations. Despite what I have just told you about the 
fact that pluripotent stem cells are not organisms and are not 
embryos, because pluripotent stem cells are derived from human 
organisms early in their development, the use of these cells 
has raised legitimate public concerns and the cells do deserve 
special ethical consideration.
    As you will hear from the final panel of witnesses, there 
is a wide range of views about the moral status of these cells 
and the developmental states from which they are derived. These 
views must, in my opinion, be taken into consideration in doing 
research with such cells.
    For example, in 1994 the NIH issued a report from its panel 
on human embryo research that carefully reviewed the medical 
benefits and the ethical quandaries that are presented by these 
and other types of experiments. Then, 2 weeks ago President 
Clinton asked the National Bioethics Advisory Commission to 
give him further advice in the wake of recent publications.
    Finally and briefly, what is the role of NIH in these 
endeavors? Federal funds were not used in the experimental work 
that you will hear about from Doctors Gearhart and Thomson 
concerning human cells. The funding of Dr. Thomson's work by 
the NIH was indeed forbidden by an amendment to our 
appropriation bill. He used embryos that were remaining in an 
in vitro fertilization clinic, donated by parents who had 
successfully achieved pregnancy in a treatment for infertility. 
Funding of Dr. Gearhart's work by the NIH would have been 
possible under existing law, but he obtained support from 
private industry instead.
    Now, I cannot overemphasize that we at the NIH see enormous 
promise in the work that is being discussed here today. We also 
believe that it is beneficial, in general, for medical research 
to be conducted in the public domain, with open dialog, with 
careful oversight, and with maximum opportunity for 
participation by the best minds in our country.
    But, we also respect existing laws. We recognize the need 
for public education about these complex issues, such as is 
occurring today, and we insist on clear guidelines and careful 
oversight for any research that might be carried out with these 
cell lines or other controversial materials under Federal law.

                           prepared statement

    Again, I thank you, Senator, for having the subcommittee 
provide a venue for this important discussion, and I will be 
very pleased to answer any questions that you might have.
    Senator Specter. Thank you very much, Dr. Varmus. We have 
turned off the red light to allow you to describe in somewhat 
greater detail the specifics here.
    [The statement follows:]

                Prepared Statement of Harold Varmus M.D.

    Mr. Chairman and Members of the Subcommittee, I am Harold Varmus, 
Director of the National Institutes of Health. I am pleased to appear 
before you to discuss recent published reports on the isolation and 
propagation of the first human pluripotent stem cell lines. These 
findings, reported by Drs. John Gearhart from Johns Hopkins University 
and James Thomson from the University of Wisconsin, bring medical 
research to the edge of a new frontier that is extraordinarily 
promising. The development of human pluripotent stem cell lines 
deserves close scientific examination, further evaluation of the 
promise of the research, and careful consideration and open discussion 
of the ethical and legal issues. I want to thank you for the 
opportunity to discuss this important issue with you and the Members of 
this Subcommittee.
    Why the excitement? For the first time, scientists have obtained 
human stem cells that can give rise to many types of cells in our body. 
Let me briefly describe these experiments. Dr. Thomson and coworkers 
derived stem cell lines from embryos donated by couples undergoing in 
vitro fertilization (IVF) as part of treatment for infertility. These 
cells were grown in culture and found to divide indefinitely and have 
the ability to form cells of the three major tissue typesendoderm 
(which goes on to form the lining of the gut), mesoderm (which gives 
rise to muscle, bone and blood) and ectoderm (which gives rise to 
epidermal tissues and the nervous system). The ability of the cells to 
specialize into the three major tissues types is an important indicator 
that these cells are pluripotent. Dr. Gearhart and his coworkers 
derived pluripotent stem cells from fetal gonadal tissue destined to 
form germ cells. When grown in culture, these cells resemble other 
types of pluripotent stem cells in that they, like the cells from Dr. 
Thomson's work, also can develop into cells of the three major tissue 
types.
                          what are stem cells?
    As policy makers proceed to consider the scientific, ethical and 
societal issues raised by this research, it is absolutely essential to 
clarify terms and definitions. There are many types of stem cells. In 
general, they all have the ability to divide (and self renew) and to 
commit to a more specialized function. There is a hierarchy of stem 
cell types. Some stem cells are more committed than others. Some stems 
cells--the pluripotent stem cell we are discussing today--have the 
ability to become many, but not all, of the cells types in the human 
body.
    Through processes we are only beginning to understand, primitive 
stem cells can be stimulated to become specialized, so that they are 
precursors to any one of many different cell types such as muscle 
cells, skin cells, nerve cells, liver cells. Unlike the stem cells from 
which they are derived, these specialized cells are ``committed'' to a 
particular function.
    All stem cells have the capability of self-renewal, i.e., they can 
continually reproduce themselves. Cells from the very earliest embryo 
(up to about the 16 cell stage) are totipotent stem cells. They are 
``totally potent'' or totally capable of forming all cells of the body, 
including the cells required to support embryonic and fetal 
development. Each cell of this early embryo has the potential to 
develop into a human being.
    After a few days of development, the early embryo forms a hollow 
ball of cells, called a blastocyst. This is the next stage of embryonic 
development. The clustered cells within this ball are called the inner 
cell mass. The cells in the inner cell mass are not totipotent. Rather, 
they are pluripotent. Pluripotent stem cells are more ``committed'' 
than totipotent stem cells. Unlike the fertilized egg, or the early 
embryo, or the intact blastocyst, neither the disaggregated inner cell 
mass nor the pluripotent stem cells derived from it (nor the 
pluripotent stem cells derived from fetal germ cells) will produce a 
human being even if returned to a woman's uterus. These cells do not 
have the potential to form a human being, because they do not have the 
capacity to give rise to the cells of the placenta or other 
extraembryonic tissues necessary for implantation, nor can they support 
fetal development in the uterus.
    During fetal development, pluripotent stem cells become even more 
committed, i.e, they have the capacity to form only one or a few 
different kinds of cells. For example, hematopoietic stem cells can 
form all the blood cells, but no other tissue types. The adult human 
being continues to harbor many types of stem cells responsible for the 
body's ability to repair some but not all tissues. Stem cells that 
permit new skin growth and renewal of blood cells are two examples.
            potential applications of pluripotent stem cells
    There are several important reasons why the isolation of human 
pluripotent stem cells is, indeed, important to science and for the 
future of public health. At the most fundamental level, pluripotent 
stem cells could help us to understand the complex events that occur 
during human development. A primary goal of this work would be the most 
basic kind of research--the identification of the factors involved in 
the cellular decision-making process that determines cell 
specialization. We know that turning genes on and off is central to 
this process, but we do not know much about these ``decision-making'' 
genes or what turns them on or off. Some of our most serious diseases, 
like cancer, are due to abnormal cell differentiation and growth. A 
deeper understanding of normal cell processes will allow us to further 
delineate the fundamental errors that cause these deadly illnesses.
    Human pluripotent stem cell research could also dramatically change 
the way we develop drugs and test them for safety and efficacy. Rather 
than evaluating safety and efficacy of a candidate drug in an animal 
model of a human disease, these drugs could be tested against a human 
cell line that had been developed to mimic the disease processes. This 
would not replace whole animal and human testing, but it would 
streamline the road to discovery. Only the most effective and safest 
candidate would be likely to graduate to whole animal and then human 
testing.
    Perhaps the most far-reaching potential application of human 
pluripotent stem cells is the generation of cells and tissue that could 
be used for transplantation, so-called cell therapies. Many diseases 
and disorders result from disruption of cellular function or 
destruction of tissues of the body. Today, donated organs and tissues 
are often used to replace the function of ailing or destroyed tissue. 
Unfortunately, the number of people suffering from these disorders far 
outstrips the number of organs available for transplantation. 
Pluripotent stem cells stimulated to develop into specialized cells 
offer the possibility of a renewable source of replacement cells and 
tissue to treat a myriad of diseases, conditions and disabilities 
including Parkinson's and Alzheimer's disease, spinal cord injury, 
stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid 
arthritis. There is almost no realm of medicine that might not be 
touched by this innovation. Let me expand on two of these examples.
    Transplant of healthy heart muscle cells could provide new hope for 
heart attack victims. The hope is to develop heart muscle cells from 
human pluripotent stem cells and transplant them into the failing heart 
muscle in order to augment the function of the heart. Preliminary work 
in mice and other animals has demonstrated that healthy heart muscle 
cells transplanted into the heart successfully repopulate the heart 
tissue and integrate with the host cells. These experiments show that 
this type of transplantation is feasible.
    In the many individuals who suffer from Type I diabetes, the 
production of insulin by the pancreas by specialized cells called islet 
cells is disrupted. There is evidence that transplantation of either 
the entire pancreas or isolated islet cells could mitigate the need for 
insulin injections. Islet cell lines derived from human pluripotent 
stem cells could be used for this critical research and, ultimately, 
for transplantation.
    While I have taken this opportunity to outline the promise of this 
research, there is much to be done before we can realize these 
innovations. First, we must do the basic research to understand the 
cellular events that lead to cell specialization in the human, so that 
we can direct these pluripotent stem cells to become the type(s) of 
tissue needed for transplantation in great numbers. And before we can 
use these cells for transplantation, we must overcome the well-known 
problem of immune rejection. Because human pluripotent stem cells 
derived from embryos or fetal tissue would likely be genetically 
different from the recipient, future research would need to focus on 
modifying human pluripotent stem cells to minimize tissue 
incompatibility. Technological challenges remain before these 
discoveries can be incorporated into clinical practice. These 
challenges, though significant, are not insurmountable.
                how are pluripotent stem cells produced?
    There are several ways to produce human pluripotent stem cells. 
These methods have been developed over the past 17 years by researchers 
working with animals. The work you will hear about today builds on this 
important basic animal research.
    As I mentioned earlier, one method of creating these pluripotent 
stem cells was described by Dr. Thomson and his coworkers. The 
techniques they used were initially developed using mice. Dr. Thomson 
first made stem cells from non-human primates. In the most recent work, 
they used inner cell mass cells from blastocyst stage human embryos 
that were created in the course of infertility treatment and donated by 
couples for research to derive stem cells. The researchers allowed cell 
division to continue in culture to the blastocyst stage and then 
removed the inner cell mass, which was cultured to derive pluripotent 
stem cells.
    Pluripotent stem cells can also be derived from fetal tissue, as 
was first done using primordial germ cells from mouse fetal tissue. Dr. 
Gearhart and coworkers isolated human primordial germ cells, the cells 
that will go on to become eggs and sperm, from 5-9 week old fetal 
tissue obtained after pregnancy termination. When grown in culture, 
these stem cells appear to be pluripotent.
    It may also be possible to make human pluripotent stem cells by 
using somatic cell nuclear transfer--the technology that received so 
much attention with the announcement of the birth of the sheep, Dolly. 
Although there has been no scientific publication of this to date, 
presumably any cell from the human body (except the egg or sperm cell) 
could be fused with an enucleated egg cell and stimulated to return to 
highly immature, pluripotent and possibly totipotent state.
                   the role of the federal government
    Federal funds were not used in either of the experiments that you 
will hear about today. First, let me first address Dr. Thomson's work 
in which cells were derived from embryos created by in vitro 
fertilization but not used for infertility treatment. This work falls 
clearly within the Congressional ban on human embryo research. NIH 
could not, and did not, support Dr. Thomson's recent work developing 
this cell line. The same restrictions do not apply to Dr. Gearhart's 
work, although it may be governed by other laws and regulations. Dr. 
Gearhart derived his pluripotent stem cells from fetal tissue from 
terminated pregnancies. The Public Health Service Act authorizes 
Federal funding of human fetal tissue research and provides safeguards 
for its conduct. The department may conduct or support research on the 
transplantation of human fetal tissue for therapeutic purposes if a 
number of statutory requirements are met. Thus, if Dr. Gearhart's 
research falls within these boundaries, NIH could have supported his 
recent work deriving pluripotent stem cells from fetal tissue, as long 
as he followed these Federal statutes and regulations. For the record, 
NIH did not, however, support any of this research.
                             ethical issues
    I have just described the science and the medical promise of 
research on the pluripotent stem cell. But the realization of this 
promise is also dependent on a full and open examination of the social 
and ethical implications of this work. The fact that these stem cells 
were produced from embryos and fetal tissue raises a number of ethical 
concerns including, for example, the need to ensure that stem cell 
research not encourage the creation of embryos or the termination of 
pregnancies for research purposes. In strict accordance with the 
President's 1994 directive, no NIH funds will be used for the creation 
of human embryos for research purposes. We also will continue to abide 
by relevant statutes.
    The ethical and social issues associated with stem cell research 
are complex and controversial and require thoughtful discourse in 
public fora to reach resolution. To this end, the President has asked 
the National Bioethics Advisory Commission to undertake a thorough 
review of the issues associated with human stem cell research, 
balancing all ethical and medical considerations.
                                summary
    The development of cell lines that may produce almost every tissue 
of the human body is an unprecedented scientific breakthrough. It is 
not too unrealistic to say that this research has the potential to 
revolutionize the practice of medicine and improve the quality and 
length of life.
    Mr. Chairman, I am grateful to you for providing a forum to present 
information about this promising arena of science and medicine. I would 
be pleased to answer any questions you might have.
                       NONDEPARTMENTAL WITNESSES

STATEMENT OF JOHN D. GEARHART, Ph.D., PROFESSOR OF 
            GYNECOLOGY AND OBSTETRICS, JOHNS HOPKINS 
            UNIVERSITY SCHOOL OF MEDICINE
    Senator Specter. I think it would be useful--we have a very 
long list of witnesses--if we invited at this time the next 
three witnesses to join the panel because we will be talking 
about very similar subjects, and then we will return to the 
question and answer session. So let me call now for Dr. John 
Gearhart, Dr. James Thomson, and Dr. Michael West to join us at 
the panel.
    Our first witness is Dr. John Gearhart, a professor of 
gynecology and obstetrics at Johns Hopkins University. Dr. 
Gearhart received his undergraduate degree from Penn State and 
his Ph.D., from Cornell University in genetics, and has some 
very fascinating results to report to us here this morning.
    So we will begin with you, Dr. Gearhart. We would like to 
observe the 5-minute time limit, leaving the maximum amount of 
time for questions and answers. Thank you for joining us and 
the floor is yours.
    Dr. Gearhart. Thank you for the opportunity to appear 
before the committee and to provide the committee with insight 
into the research in which we have been engaged for the last 5 
years. I feel strongly that the medical benefits of this 
research will be enormous and that we are excited about its 
potential.
    Dr. Varmus has covered the salient features of embryonic or 
pluripotent stem cells. I would like to reinforce a few points 
and then I would like to tell you how we performed our 
experiments.
    The most important point I think to be reinforced is the 
fact that, although these cells can form many different cell 
types, they are unable by themselves to form an embryo or a 
human being.
    A bit of perspective. For the past 20 years I have been 
involved in Down Syndrome research. This research has been 
sponsored through the National Institutes of Health, and one of 
the conclusions from our studies of 20 years is that many of 
the events that lead to the abnormalities that one sees in Down 
Syndrome occur very early during pregnancy, very early in 
embryogenesis, at stages that we cannot have access to.
    In studies from the mouse using embryonic stem cells, we 
are able to look at very early developmental events utilizing 
these cells, and thus our desire to establish human cells with 
which we can study aspects of early development, focusing on 
Down Syndrome.
    [Chart.]
    The procedure that we used in the laboratory is depicted on 
the first placard. We obtained from autopsy material, fetal 
autopsy material, this structure here--I hope I do not blind 
somebody--which is a very small piece of tissue in which the 
primordial germ cells reside from the period of 5 to 7 weeks 
post-fertilization. This piece of tissue is dissociated, placed 
in culture under certain conditions such that these cells will 
grow, the germ cells, and will convert, for lack of a 
scientific term, into a pluripotential stem cell.
    I want to emphasize that this technology was first 
developed in the mouse and we adapted it to the human. We did 
not have to work it out in the human per se, just adapt it.
    These cells, as depicted in our publication, have many of 
the properties of embryonic stem cells. Our studies have 
followed Federal, that is FDA and NIH, guidelines, State 
guidelines, and institutional guidelines. Our research has been 
rigorously reviewed annually by the Johns Hopkins School of 
Medicine institutional review board, which considers not only 
scientific merit but also ethical considerations of the work.
    What of the application of this work? Well, we have 
mentioned several times here its use in tissue transplantation, 
birth defects studies, et cetera. My main interest coming into 
this has been in aspects of birth defects, and directed 
primarily to Down Syndrome.
    [Chart.]
    I would like to show you on the next placard, though, some 
more recent results. What is depicted here are images of mature 
human neurons that have been grown from embryonic stem cells in 
culture. Embryonic stem cells have been grown for a period of 3 
months and then treated over a period of 5 days so as to 
encourage these cultures to form neurons. They are human, they 
have the features of neurons, and this would go to show, I 
think, some of the power of this technology from the standpoint 
of being able to derive these different tissues in culture 
which could perhaps then be used for tissue transplantation 
studies.

                           prepared statement

    In conclusion, I firmly believe that this research holds 
the potential for treatments of catastrophic and debilitating 
diseases and injuries that affect millions of Americans. What 
is needed to realize this potential as soon as possible is 
Federal support and oversight such as that that the NIH could 
provide and that the investigators in this area not be 
restricted in their endeavors, so that we may bring the 
products of this technology to the patients as soon as 
possible.
    Thank you, Mr. Chairman.
    Senator Specter. Thank you very much, Dr. Gearhart.
    [The statement follows:]

                  Prepared Statement of John Gearhart

    My name is John Gearhart and I am a Professor of Gynecology and 
Obstetrics at the Johns Hopkins University School of Medicine. My 
research interests are in how genes regulate the formation of tissues 
and embryos. For the past 18 years my research has focused on Down 
Syndrome in attempts to determine the causes of the birth defects 
characteristic of this syndrome, with special emphasis on mental 
retardation. As a result of our studies, it is apparent that the events 
leading to the many birth defects characteristic of the syndrome occur 
in the very early stages of the embryo's development, at stages not 
accessible for study. Because of this limitation, I sought to develop 
another approach that would enable us to study theses key events. The 
approach I sought was to use human pluripotential stem cells (hPSC). 
HPSCs will enable us to study the formation of specific tissues that 
would reveal the cellular mechanisms resulting in the pathogenesis 
found in Down Syndrome. Knowing how and when abnormalities arise will 
enable us to design therapies to ameliorate the devastating effects of 
developmental disabilities and enable individuals to have a better 
quality of life.
    In order to use human stem cells in the study of birth defects, the 
first step was to culture hPSCs in the laboratory, something that had 
not been done before we began our attempts in 1993. Over several years 
I was able to put together a research team consisting of Drs. Michael 
Shamblott, Peter Donovan, John Littlefield, Paul Blumenthal, and George 
Huggins, with the excellent technical support of Elizabeth Bugg and 
Joyce Axelman. This past year, Shunping Wang, a graduate student, 
joined the team. On November 10th of this year we reported in the 
Proceedings of the National Academy of Sciences our results on the 
culturing of cells with properties of hPSCs. A copy of that paper is 
submitted with this testimony.
    I would like to place our recent work on hPSCs in perspective. 
hPSCs are unique cells in that they have both the capacity to form any 
of the over 200 different cell type in the body and to self-renew the 
stem cell population. These properties can be realized in the 
laboratory, that is, the stem cells can be grown indefinitely in tissue 
cultures dishes and, under appropriate culture conditions, they will 
form other cell types. It is important to note that while these cells 
have the capacity to form a variety of cell types, they cannot form 
embryos. Our laboratory used primordial germ cells (PGCs) as starting 
material to derive the stem cells. PGCs are cells whose descendants are 
sperm and eggs. PGCs were collected from autopsy material of 
therapeutic pregnancy terminations and placed in tissue culture. Over a 
period of two weeks in culture the PGCs develop into pluripotential 
stem cells.
    It has been well documented from animal studies that PSCs have full 
developmental potential. Both in animals and in the culture dish, these 
cells can form a wide variety of cell types including blood cells, 
blood vessels, skeletal and cardiac muscle, and nerve tissue have been 
shown to develop from these cells in the laboratory. I have presented 
examples here today of nerve cells produced in the laboratory from the 
human stem cells.
    Although we can demonstrate a variety of cell types formed in the 
laboratory from these cells, we do not yet know how to control which 
cell types will form. This is one of the next challenges, to determine 
how to direct all the stem cells in the culture dish to form specific 
cell types, such as pancreatic islet cells, cholinergic neurons, 
dopaminergic neurons, cardiac muscle, lymphocytes, etc. These cell 
types are at risk in some of our more devastating diseases and a tissue 
culture source would be ideal for therapies that are mentioned below. 
The time frame for accomplishing this phase of the research will be 
directly correlated to the research efforts of laboratories involved in 
this research effort. Only a supportive research environment, both in 
terms of policy and resources, will move this work forward rapidly.
    What is to be gained from studies using hPSCs? I mentioned that my 
group's initial motivation in attempting to isolate a human pluripotent 
line was to provide a powerful tool for determining the bases of the 
abnormalities seen in Down Syndrome, something we have been studying 
for two decades. We have learned that the bases for many of the 
features of this syndrome are initiated very early in the embryo. 
Without a human pluripotential cell line, it would be impossible to 
study the cells and tissue in which these features are initiated. 
However, with this tool scientists may better understand mechanisms 
behind the formation, and malformation, of distinct tissue types. With 
this understanding, biomedical science may someday be able to alleviate 
the worst of these features, such as mental retardation, in Down 
Syndrome as well as other genetically based developmental 
abnormalities. Without question, hPSCs will have the greatest impact on 
medicine through their utilization in tissue transplantation therapies 
in which tissues or cells are engrafted into organs, which have been 
destroyed through disease or injury. Tissue transplantation therapy has 
become increasingly important in the last two decades. Traditional 
tissue transplantation therapies utilize such tissues as bone marrow, 
bone, skin, etc. However, as each day passes, new therapies are 
envisioned which tax current donation protocols. An example of such a 
novel therapy is the use of tissue transplantation for the treatment of 
Parkinson's Disease. This therapy began with the transplantation of the 
patient's own dopaminergic adrenal medullary tissue into the 
degenerating portions of the brain. The next development in the 
treatment of Parkinson's was the utilization of fetal neural tissue 
instead of adrenal tissue. The fetal tissue, due to its more plastic 
state and its ability to grow and integrate into the host environment, 
offers an effective treatment of Parkinson's disease.
    With the rise of these novel tissue transplantation therapies, 
equally novel graft resources have been sought. These include adult-
derived stem cells, such as those found in muscle; genetically 
engineered graft tissue, non-human animal tissue, human fetal tissue 
and, finally, the use of hPSCs. Eventually, through our abilities to 
control what cell types are formed from the stem cells in the 
laboratory and through the optimization of transplantation protocols, 
the hPSCs will enable a panoply of new treatments. Along with 
Parkinson's disease, it is likely that the symptoms of other 
neurodegenerative disorders and injuries, such as Alzheimer's disease, 
Huntington disease, stroke and spinal cord injury could be effectively 
ameliorated and quality of life improved. Neurodegenerative disorders 
are by no means the only conditions to which the use of human 
pluripotent stem cells could apply. The bankable pluripotential stem 
cells could be induced to form insulin-producing pancreatic b-cells to 
make diabetics less dependent on insulin injection. Muscle stem cells 
could also conceivably be produced from human pluripotential stem cells 
in a large enough yield to help those with muscular dystrophies regain 
better motor control. Cardiac muscle stem cell could be derived and 
subsequently used to help in the treatment of degenerative heart 
disease and perhaps decrease the necessity of more complicated and more 
costly whole organ transplantation.
    One of the major limitations of tissue transplantation is the issue 
of graft rejection. The patient's immune system must be compromised to 
allow for the presence of the graft. This generally involves the use of 
powerful drugs with side affects. In animal studies, it has been found 
that stem cells can be genetically manipulated so as to modify graft 
rejection. It may eventually be possible to produce universal donor 
cell lines in the laboratory through the use of hPSCs.
    The capability of hPSCs to form a variety of cell types, their 
ability to self-renew in the laboratory (and to be banked) and their 
ability to be genetically manipulated to enhance their transplantation 
efficiency, all support the contention that these cells will be an 
invaluable resource in transplantation medicine.
    Our research has been reviewed and approved annually by the 
Institutional Review Board of the Johns Hopkins University School of 
Medicine whose composition includes ethicists, religious leaders, lay 
people, and doctors. This committee insures that we are in compliance 
with all Federal, State and institutional requirements, from patient 
consent, to record keeping, to safety. This committee considers ethical 
issues as well as the scientific merit and research protocols. Our 
research on stem cells has been supported through endowment funds to my 
division in Gynecology and Obstetrics until last year, when we received 
funding from Geron Corporation of Menlo Park, CA. My involvement with 
Geron Corporation has been reviewed and approved by the Conflict-of-
Interest Committee for the Johns Hopkins University School of Medicine.
    In conclusion, research with pluripotent human stem cells holds 
enormous promise for treatments of catastrophic and debilitating 
diseases and injuries affecting millions of Americans. To realize the 
full medical potential of these cells, it is imperative that this work 
goes forward in a supportive research environment with appropriate 
overview and regulation. It is my opinion that this work should be 
eligible for Federal funds and that the National Institutes of Health 
should be given the responsibility to develop policy and guidelines, 
review research applications, and award research grants on human 
pluripotential stem cells. Only through the mechanism of NIH oversight 
and support will the American people be assured that the medical 
benefits of these cells for alleviating suffering will progress as 
rapidly as possible and that any concerns that they may have will be 
taken into account.
    Thank you for the opportunity to address the committee on this 
important issue.
    This statement was prepared with the assistance of Brian Edwards.
STATEMENT OF JAMES THOMSON, Ph.D., ASSOCIATE RESEARCH 
            ANIMAL VETERINARIAN, WISCONSIN REGIONAL 
            PRIMATE RESEARCH CENTER
    Senator Specter. We turn now to Dr. James Thomson, 
Associate Research Animal Veterinarian at the Wisconsin 
Regional Primate Research Center, a graduate of the University 
of Pennsylvania in veterinary medicine, a Ph.D. in molecular 
biology, author of numerous scientific publications in his 
field.
    Thank you for joining us, Dr. Thomson. The floor is yours.
    Dr. Thomson. I would like to thank the committee for 
inviting me. What I have to say overlaps a great deal with what 
Dr. Varmus and Dr. Gearhart said, so I will be fairly brief.
    My group has recently reported the derivation of human 
embryonic stem cell lines. As you have heard, these are 
undifferentiated cells. This means that they do not look like 
the cells that make up the adult body. They are not yet 
committed to become specific things. These undifferentiated 
cells----
    Senator Specter. People are straining to hear you in the 
audience, so would you put the microphone closer, please.
    Dr. Thomson. These undifferentiated cells can proliferate 
in tissue culture indefinitely. That means we can make as many 
of these cells as we want to and we know no biological limit to 
the numbers of these cells we can make.
    What is important about these cells is that, even after 
prolonged culture for months and potentially years, they 
maintain the ability to form many, if not all, of the cells 
that make up the adult body.
    Now, our cells differ in their source, where they came 
from, compared to Dr. Gearhart's. Our cells were derived from 
the pre-implantation embryo. They were derived from in vitro-
fertilized produced embryos, and these were produced for 
clinical purposes, but they are in excess of the clinical needs 
of the couples and the couples donated them specifically for 
this project instead of actually discarding them. The informed 
consent process was detailed and specified the purpose of the 
research, its context, and its implications.
    Now, as you have heard, human embryonic stem cells are 
important because they could provide large purified populations 
of human cells, such as muscle cells, pancreatic cells, or 
neurons for transplantation therapies. Many diseases, including 
diseases such as juvenile onset diabetes and Parkinson's 
disease, result from the death or dysfunction of just one or a 
few cell types, and the replacement of those cell types can 
potentially offer life-long treatments.
    These cells are also important because they will offer 
insights in development events that cannot be studied directly 
in the intact human embryo, but which have important 
consequences in clinical areas, including birth defects and 
fertility and pregnancy loss, and John Gearhart touched on Down 
Syndrome, for example.
    Screening tests that use specific ESL derivatives will 
allow the identification of new drugs, the identification of 
genes that could be used for tissue regeneration therapies, and 
the identification of toxic compounds.
    Although the long-term potential for human therapies 
resulting from human ESL cell-line research is enormous, these 
therapies will take years to develop. Significant advances in 
developmental biology and transplantation medicine are 
required, but I believe that therapies resulting from human ESL 
research will become available within my lifetime.
    How soon such therapies will be developed will depend on 
whether there is public support of research in this area. 
Private companies will have an important role in bringing new 
ESL-related therapeutics to the marketplace. However, the 
current ban in the United States on the use of NIH funding for 
human embryo research discourages the majority of the best U.S. 
researchers from advancing this promising area of medical 
research.
    Human pre-implantation embryo research was reviewed in 
depth by the NIH human embryo research panel 1994. The NIH 
panel recognized the therapeutic promise of human embryo 
research, while recognizing that the human embryo warrants 
serious moral considerations as a developing form of human 
life. For these reasons the panel concluded in part:

                     Federal Funding and Regulation

    It is in the public interest that the availability of 
Federal funding and regulation should provide consistent 
ethical and scientific review for this area of research. The 
panel believes that, because the pre-implantation embryo 
possesses qualities requiring moral respect, research involving 
the ex utero pre-implantation embryo must be carefully 
regulated and consistently monitored.

    I agree with these conclusions.

                           prepared statement

    This hearing on embryonic stem cell research is timely and 
I hope that I can help you better understand the work we have 
done and its medical and ethical implications. I would be 
pleased to answer any of your questions.
    Senator Specter. Thank you very much, Dr. Thomson.
    [The statement follows:]

                 Prepared Statement of James A. Thomson

                                overview
    My name is James Thomson and I'm a developmental biologist at the 
University of Wisconsin-Madison. My group has recently reported the 
derivation of human Embryonic Stem (ES) cells that can proliferate 
indefinitely in tissue culture and yet maintain the potential to form 
many, and possibly all, adult cell types. Human ES cells thus provide a 
potentially unlimited source of specific differentiated cell types for 
basic biological research, pharmaceutical development, and 
transplantation therapies. These human ES cell lines were derived from 
in vitro fertilized embryos before the formation of any fetal 
structures. These embryos were produced by in vitro fertilization for 
clinical purposes, but were in excess of clinical needs and were 
donated after informed consent. The informed consent process was 
detailed and specified the purposed of the research, its context, and 
its implications.
    Human ES cell lines are important because they could provide large, 
purified populations of human cells such as heart muscle cells, 
pancreatic cells, or neurons for transplantation therapies. Many 
diseases, such as juvenile onset diabetes mellitus and Parkinson's 
disease, result from the death or dysfunction of just one or a few cell 
types, and the replacement of those cells by transplantation could 
offer lifelong treatment. Human ES cells are also important because 
they will offer insights into developmental events that cannot be 
studied directly in the intact human embryo, but which have important 
consequences in clinical areas, including birth defects, infertility, 
and pregnancy loss. Screening tests that use specific ES cell 
derivatives will allow the identification of new drugs, the 
identification of genes that could be used for tissue regeneration 
therapies, and the identification of toxic compounds.
    Although the long-term potential for human therapies resulting from 
human ES cell line research is enormous, these therapies will take 
years to develop. Significant advances in developmental biology and 
transplantation medicine are required, but I believe that therapies 
resulting from human ES cell research will become available within my 
lifetime. How soon such therapies will be developed will depend on 
whether there is public support of research in this area. Private 
companies will have an important role in bringing new ES cell-related 
therapeutics to the marketplace; however, the current ban in the U.S. 
on the use of Federal funding for human embryo research discourages the 
majority of the best U.S. researchers from advancing this promising 
area of medical research. Human preimplantation embryo research was 
reviewed in depth by the National Institutes of Health (NIH) Human 
Embryo Research Panel in 1994. The NIH Panel recognized the therapeutic 
promise of human embryo research while recognizing that the human 
embryo warrants serious moral consideration as a developing form of 
human life. For these reasons, the panel concluded in part, ``It is in 
the public interest that the availability of Federal funding and 
regulation should provide consistent ethical and scientific review for 
this area of research. The Panel believes that because the 
preimplantation embryo possesses qualities requiring moral respect, 
research involving the ex utero preimplantation human embryo must be 
carefully regulated and consistently monitored.'' I agree with these 
conclusions. This hearing on embryonic stem cell line research is 
timely. I hope I can help you better understand the work we have done 
and its medical and ethical implications, and I would be pleased to 
answer any questions that you have.
                  what are human embryonic stem cells?
    In the adult mammal, cells with a high turnover rate are replaced 
in a highly regulated process of proliferation, differentiation, and 
programmed cell death from undifferentiated adult ``stem cells''. 
Tissues from which stem cells have been extensively studied include 
blood, skin, and the intestine. In the human small intestine for 
example, approximately one hundred billion cells are shed and must be 
replaced daily. Although various definitions have been proposed, 
characteristics of adult stem cells generally include: (i) prolonged 
proliferation, (ii) self-maintenance, (iii) generation of large numbers 
of progeny with the principle phenotypes of the tissue, (iv) 
maintenance of developmental potential over time, and (v) the 
generation of new cells in response to injury. Thus, stem cells in the 
adult sustain a relatively constant number of cells and cell types. 
Several properties of adult stem cells limit their therapeutic 
potential. First, all adult stem cells are committed to becoming a 
relatively restricted number of cell types. Second, although adult stem 
cells can divide for prolonged periods, cell division can occur only a 
finite number of times, so there is a limit to how much they can be 
expanded in tissue culture. Third, the sustainable culture of adult 
stem cells has not yet been achieved. And fourth, several tissues of 
clinical importance, such as the heart, completely lack stem cells in 
the adult. Thus, after a heart attack, when heart muscle dies, there is 
no regeneration of heart muscle, only the formation of non-functional 
scar tissue.
    In contrast to the adult, embryonic cell proliferation and 
differentiation elaborates an increasing number of cells and cell 
types. In mammals, each cell of the cleavage stage embryo has the 
developmental potential to contribute to any embryonic or 
extraembryonic cell type, but by the blastocyst stage, cells on the 
outside of the embryo (the trophectoderm) are committed to a particular 
cell type found in the placenta (Figure 1). The cells on the inside of 
the blastocyst (the inner cell mass) contribute to all the tissues of 
the embryo proper. Soon after the blastocyst stage, cells of the inner 
cell mass develop into cells that are developmentally restricted to 
particular lineages. Because the cells of the inner cell mass 
proliferate and replace themselves in the intact embryo for a very 
limited time before they become committed to specific lineages, they do 
not satisfy the criteria for stem cells that are applied to adult 
tissues. In contrast, if the inner cell mass is removed from the normal 
embryonic environment and dissociated under appropriate conditions, the 
cells will remain undifferentiated, replace themselves indefinitely, 
and maintain the developmental potential to contribute to all adult 
cell types. Thus, these inner cell mass-derived cells satisfy the 
criteria for stem cells outlined above, and they are referred to as 
embryonic stem (ES) cells. The derivation of mouse ES cells was first 
reported in 1981. We have recently described the isolation of human ES 
cell lines that satisfy the following criteria for ES cells: (i) 
derivation from the pre- or per-implantation embryo, (ii) prolonged 
undifferentiated proliferation, and (iii) stable developmental 
potential after prolonged culture to form differentiated derivatives of 
all three embryonic germ layers (endoderm, mesoderm, and ectoderm) 
which are the three basic lineages that give rise to all of the cells 
of the adult. Cells we have already observed to differentiate from 
human ES cell lines have included gut epithelium (endoderm), cartilage, 
bone, and smooth and striated muscle (mesoderm); and neural epithelium, 
embryonic ganglia, and stratified squamous epithelium (ectoderm).
                   why are human es cells important?
    Human ES cell lines could offer insights into developmental events 
that cannot be studied directly in the intact human embryo or in other 
species, but which have important consequences in clinical areas, 
including birth defects, infertility, and pregnancy loss. Particularly 
in the early post-implantation period, knowledge of normal human 
development is largely restricted to the description of a limited 
number of sectioned embryos and to analogies drawn from the 
experimental embryology of other species. Although the mouse is the 
mainstay of experimental mammalian embryology, early structures 
including the placenta, extraembryonic membranes, and the egg cylinder 
all differ significantly from those of the human embryo. Human ES cell 
lines will be particularly valuable for the study of the development 
and function of tissues that differ between mice and humans.
    Elucidating the mechanisms that control differentiation will 
facilitate the directed differentiation of ES cells to specific cell 
types. The standardized production of large, purified populations of 
normal human cells such as heart muscle cells and neurons will provide 
a potentially limitless source of cells for drug discovery and 
transplantation therapies. For example, large purified populations of 
ES cell-derived heart muscle cells could be used to find new drugs to 
treat heart disease. Many diseases, such as Parkinson's disease and 
juvenile onset diabetes mellitus, result from the death or dysfunction 
of just one or a few cell types. The replacement of those cells could 
offer lifelong treatment. In addition to Parkinson's disease and 
juvenile onset diabetes, the list of diseases potentially treated by 
this approach is long, and includes myocardial infarction (heart muscle 
cells and blood vessels) atherosclerosis (blood vessels) leukemia (bone 
marrow), stroke (neurons), burns (skin) and osteoarthritis (cartilage). 
For the foreseeable future, these therapies will involve the repair of 
organs by the transplantation of cells or simple tissues, but not the 
replacement of entire organs.
    Strategies to prevent immune rejection of the transplanted cells 
need to be developed, but could include banking ES cell lines with 
defined major histocompatibility complex backgrounds or genetically 
manipulating ES cells to reduce or actively combat immune rejection. 
Significant advances in basic developmental biology are required to 
direct ES cells efficiently to lineages of human clinical importance. 
However, progress has already been made in the in vitro differentiation 
of mouse ES cells to neurons, hematopoietic cells, and cardiac muscle.
      why is the derivation of human es cell lines controversial?
    The derivation of human ES cells lines is controversial both 
because of the use of human embryos, and because of the properties of 
ES cell lines. We have derived human ES cell lines from in vitro 
fertilized embryos at a stage before implantation (the blastocyst 
stage) and before the formation of any fetal structures. These embryos 
were produced by in vitro fertilization for clinical purposes, but were 
in excess of clinical needs. Instead of discarding these embryos, 
couples donated them specifically for ES cell derivation after informed 
consent. The use of human embryos generated by in vitro fertilization 
for any research purpose raises complex ethical issues, and it is 
beyond the scope of this testimony to review the wide range of views on 
this subject. Research on human preimplantation embryos has been 
reviewed in depth by national panels in Britain, Canada, and the United 
States. In Britain, some research on human preimplantation embryos is 
allowed, but it is very carefully monitored and regulated, regardless 
of whether public or private funds are used. The derivation of human ES 
cell lines is already being publicly funded in Britain. In the U.S., 
the most recent and complete review of human preimplantation embryo 
research was completed by the National Institutes of Health (NIH) Human 
Embryo Research Panel in the fall of 1994. Although the guidelines 
suggested by the NIH panel do not have the force of law, we followed 
those guidelines in our derivation of human ES cell lines, as no other 
Federal guidelines currently exist for privately funded human embryo 
research. The derivation of human ES cell lines was specifically 
addressed by the NIH Panel, and it was recommended as acceptable for 
Federal funding, as long as embryos were not fertilized expressly for 
that purpose. The subsequent ban on Federal funding for research on 
human preimplantation embryos has prevented the NIH from funding the 
derivation of human ES cell lines, and has prevented the NIH from 
regulating and monitoring research in this area. The NIH Panel both 
recognized the therapeutic promise of human embryo research and 
recognized that the human embryo warrants serious moral consideration 
as a developing form of human life. For these reasons, the panel 
concluded in part, ``It is in the public interest that the availability 
of Federal funding and regulation should provide consistent ethical and 
scientific review for this area of research. The Panel believes that 
because the preimplantation embryo possesses qualities requiring moral 
respect, research involving the ex utero preimplantation human embryo 
must be carefully regulated and consistently monitored.''
    Human ES cell lines are not the equivalent of an intact human 
embryo. If a clump of ES cells was transferred to a woman's uterus, the 
ES cells would not implant and would not form a viable fetus. The 
recent cloning of sheep and mice by the transfer of an adult cell 
nucleus to an enucleated oocyte demonstrates that at least some adult 
cells are totipotent (capable of forming an intact embryo that is 
capable of developing to term). If nuclear transfer from adult cells to 
enucleated oocytes allows development to term in humans, then the 
transfer of a nucleus from an ES cell to an enucleated oocyte might 
also result in a viable embryo. However, if someone wanted to clone a 
specific famous or infamous individual, the transfer of a nucleus from 
adult cell would have to be used, not a nucleus from an ES cell. One of 
the major uses of mouse ES cells has been to genetically modify the 
germ line (gametes) of mice in very specific ways. However, because of 
the significant reproductive differences between mice and humans, and 
the inefficiency of this method of modifying the germ line, human ES 
cells do not increase the potential for modifying the human germ line. 
As has already been demonstrated in domestic animal species such as the 
cow and sheep, nuclear transfer techniques allow a much more efficient 
way to modify the germ line of species with long generation times. 
Thus, if someone wanted to genetically modify the human germ line, 
there are already other approaches that would be quicker and more 
efficient than using human ES cells. The NIH Human Embryo Research 
Panel included recommendations against research involving nuclear 
transfer to enucleated human oocytes or zygotes followed by transfer to 
a uterus, and any formation of chimeras with human embryos; these 
recommendations would effectively preclude the use of ES cells for 
human cloning or modifying the human germ line.
STATEMENT OF MICHAEL WEST, Ph.D., PRESIDENT AND CHIEF 
            EXECUTIVE OFFICER, ADVANCED CELL TECHNOLOGY
    Senator Specter. We now turn to Dr. Michael West, president 
and chief executive officer of the Advanced Cell Technology. 
Dr. West has a Ph.D., in cell biology from Baylor College of 
Medicine and has recently noted the use of cloning techniques 
to create an embryo out of human and cow cells.
    We appreciate you joining us, Dr. West, and look forward to 
your testimony.
    Dr. West. Thank you, Mr. Chairman, members of the 
subcommittee. I would like to just expand on a few salient 
points. You have my written testimony.
    First, I think it is important to emphasize what the aims 
of this research we are discussing today is. The goal is to 
solve unsolved problems in transplantation medicine. Currently 
estimates are that upward of half of all health care 
expenditures in the United States, so that is upwards of $400 
billion, can in one way or another be attributed to costs 
associated with transplantation. Even coronary artery bypass, 
after all, is a transplantation procedure.
    These costs are expected to be aggravated dramatically with 
the aging of the population. As you know, our population is 
greying at an alarming rate, such that perhaps up to a 
sevenfold increase in the number of elderly between 1980 and 
the year 2030 will occur. So with this is thought to be a dire 
need for transplantable tissues. You may know that upwards of 
ten people die every day awaiting a transplantable organ which 
they do not receive. Many others die for lack of hope of a 
transplant that could cure their disease. However, their 
disease could be possibly treated with the technologies we are 
discussing today.
    The problem is two things. First is the availability of 
tissues. They are simply not available. Many primitive 
undifferentiated cell types that would be necessary to treat 
disease like heart failure are not available. The discovery of 
the human embryonic stem cells and the embryonic germ cell may 
go a long ways toward supplying the unsupplied demand.
    But a second problem is histocompatibility. The cells that 
Dr. Gearhart and Thomson described have the potential to be 
genetically engineered to be universal donor cells, so that 
cells that they derive could potentially be used for all the 
transplantation of the future. However, there is a distinct 
risk that that is not a practically achievable goal. We simply 
do not know today for sure a technology to make these cells 
universal donor cells. They may indeed, for the foreseeable 
future at least, require immunosuppressive therapies, drugs 
that carry with them an inherent risk of rejection, despite 
immunosuppression and life-threatening complications, including 
death.
    Now, a promising solution which could potentially 
revolutionize transplantation medicine would be to combine this 
embryonic stem cells technology with nuclear transfer 
technology or cloning technology. Now, the concept here would 
be that we would take the patient's own cell and fuse it with 
an egg or oocyte cell that has had its nucleus removed. The 
belief is that this nuclear transfer procedure can 
dedifferentiate the cell, taking it back to this primitive 
state where it can become any cell type, and in addition 
actually rejuvenates the cell, makes the cell young again. So 
for elderly patients with degenerative disease this procedure 
may indeed provide some dramatic improvements in therapy.
    The remaining problem, however, is that we simply cannot 
practically achieve a means of sourcing human oocytes for a 
large-scale solution to the problems of transplantation. 
Sourcing human oocytes, we have potentially problematic and 
cost issues, quality control, and risk to the donor.
    So in 1996 Advanced Cell Technology began studies to 
determine whether we could use an animal oocyte as a means of 
dedifferentiating a human cell. Now, this is not cloning 
technology. We are not cloning human beings. The intent is not 
to clone human beings and we are against the cloning of a human 
being.
    The intent, however, would be to take an animal oocyte and 
completely remove all genetic information by removing its 
genomic nucleus that contains all of the DNA and, using that 
oocyte stripped of its DNA, to reprogram a human somatic cell, 
then making cells that would be fully compatible with the 
patient.

                           prepared statement

    This work was done in 1996. In 1997, as you know, there was 
the announcement of the cloning of Dolly, and on March 4, 1997, 
President Clinton asked for a voluntary moratorium in the 
public and private sectors on human cloning. We felt that it 
would be inappropriate for us to continue this research without 
further guidelines and backed off from the research. However, 
we recently announced these preliminary results in the hope of 
stimulating debate, to hopefully receive guidelines to allow 
this important technology to move forward. We believe that it 
would be possible to address one of the most important, 
significant, and life-threatening problems in medicine today 
that could be addressed with transplantation.
    Thank you.
    Senator Specter. Thank you very much, Dr. West.
    [The statement follows:]

                 Prepared Statement of Michael D. West

    Mr. Chairman and members of the Subcommittee on Labor, Health and 
Human Services and Education, my name is Dr. Michael D. West and I am 
the President and Chief Executive Officer of Advanced Cell Technology a 
biotechnology company based in Worcester, Massachusetts. A copy of my 
curriculum vitae is presented in Appendix A.
                              introduction
    I am pleased to testify today in regard to the new opportunities 
and challenges associated with human embryonic stem (ES) cell and 
nuclear transfer (NT) technologies. By way of introduction, I believe 
it is important to bring to mind the context of these new 
opportunities. We are approaching a period in our national history of 
unparalleled growth of the elderly sector of the population. The aging 
of the baby boom population along with a general increase in the number 
of aged people is expected to increase the number of the elderly 
sevenfold between 1980 and 2030 A.D. And since the aged use a 
disproportionately high percentage of healthcare, this ``graying of 
America'' is likely to greatly strain our national resources. It has 
been estimated that transplantation procedures currently account for 
nearly half of our health care expenditures, approaching $400 billion 
annually. This is likely to grow even larger with the aging of our 
population and result in a marked increase in the demand for 
transplantation. The increased incidence of age-related degenerative 
disease will likely lead to conflicts of economics, ethics, and 
aesthetics as we struggle to find a humane and practical means of 
treating the ailing. Concrete examples of tissues needed will likely 
include: heart tissue for heart failure, arrhythmias, and ischemic 
damage, cartilage for arthritis, neurons for Parkinson's disease, 
kidney cells for kidney failure, liver cells for cirrhosis and 
hepatitis, skin for burns and ulcers, and bone marrow transplantations 
for cancer to name only a few. While current procedures are partially 
successful in alleviating human suffering, these procedures are limited 
by two major difficulties: (1) the availability of the needed cell or 
tissue type, and (2) the histocompatibility of the transplanted 
tissues. As a result, thousands of patients die every year for the lack 
of transplantable cells and tissues and projections from the Bureau of 
the Census suggest this shortage will worsen with the aging of our 
population.
                             human es cells
    Human ES cell technologies may greatly improve the availability of 
diverse cell types. Human ES cells are unique in that they stand near 
the base of the developmental tree. These cells are frequently 
designated ``totipotent'' stem cells, meaning that they are potentially 
capable of forming any cell or tissue type needed in medicine. These 
differ from previously-isolated stem cells that are ``pluripotent'' 
that is, capable of forming several, but only a limited number, of cell 
types. An example of pluripotent stem cells are the bone marrow stem 
cells now widely used in the treatment of cancer and other life-
threatening diseases.
    With appropriate funding of research, we may soon learn to direct 
these cells to become vehicles of lifesaving potential. We may, for 
instance, become able to produce neurons for the treatment of 
Parkinson's disease and spinal cord injury, heart muscle cells for 
heart failure, cartilage for arthritis and many others as well. This 
research has great potential to help solve the first problem of tissue 
availability, but the technologies to direct these cells to become 
various cell types in adequate quantities remains to be elucidated. 
Because literally hundreds of cell types are needed, thousands of 
academic research projects need to be funded, far exceeding the 
resources of the biotechnology industry.
    As promising as ES cell technology may be, it does not solve the 
second problem of histocompatibility. As shown in Figure 1, human ES 
cells obtained from embryos derived during in vitro fertilization 
procedures, or from fetal sources, are essentially cells from another 
individual (allogeneic). Several approaches can be envisioned to solve 
the problem of histocompatibility. One approach would be to make vast 
numbers of human ES cell lines that could be stored in a frozen state. 
This ``library'' of cells would then offer varied surface antigens, 
such that the patient's physician could search through the library for 
cells that are as close as possible to the patient. But these would 
likely still require simultaneous immunosuppression that is not always 
effective. In addition, immunospuppresive therapy carries with it 
increased cost, and the risk of complications including malignancy and 
even death.
    Another theoretical solution would be to genetically modify the 
cultured ES cells to make them ``universal donor'' cells. That is, the 
cells would have genes added or genes removed that would ``mask'' the 
foreign nature of the cells, allowing the patient's immune system to 
see the cells as ``self''. While such technologies may be developed in 
the future, it is also possible that these technologies may carry with 
them unacceptably high risks of rejection or other complications that 
would limit their practical utility in clinical practice.
    Given the seriousness of the current shortage of transplantable 
cells and tissues, the FDA has demonstrated a willingness to consider a 
broad array of options including the sourcing of cells and indeed whole 
organs from animals (xenografts) although these sources also pose 
unique problems of histocompatibility. These animal cells do have the 
advantage that they have the potential to be genetically engineered to 
approach the status of ``universal donor'' cells, through genetic 
engineering. However as described above, no simple procedure to confer 
such universal donor status is known. Most such procedures are still 
experimental and would likely continue to require the use of drugs to 
hold off rejection, drugs that add to health care costs, and carry the 
risk of life-threatening complications.
                          therapeutic cloning
    A promising solution to this remaining problem of 
histocompatibility would be to create human ES cells genetically 
identical to the patient. While no ES cells are known to exist in a 
developed human being and are therefore not available for treatment, 
such cells could possibly be obtained through the procedure of somatic 
cell nuclear transfer (NT). In this still largely theoretical 
procedure, body cells from a patient would be fused with an egg cell 
that has had its nucleus (including the nuclear DNA) removed. This 
would theoretically allow the production of a blastocyst-staged embryo 
genetically identical to the patient that could, in turn, lead to the 
production of ES cells identical to the patient. In addition, published 
data suggests that the procedure of NT can ``rejuvenate'' an aged cell, 
restoring the proliferative capacity inherent in cells at the beginning 
of life. Therefore, NT as applied to the production of therapeutic stem 
cells could have valuable and important applications in the treatment 
of age-related degenerative diseases.
    The use of somatic cell nuclear transfer for the purposes of 
dedifferentiating a patient's cells for purposes of obtaining 
undifferentiated stem cells has been designated ``Therapeutic Cloning'' 
in the United Kingdom. This terminology is used to differentiate this 
clinical indication from the use of NT for the cloning of a child which 
in turn is designated ``Reproductive Cloning'' in the United Kingdom. 
In the United Kingdom, the use of NT for therapeutic cloning is being 
encouraged while legislation has been passed to prohibit reproductive 
cloning. As promising as NT technologies may be in the arena of 
therapeutic cloning, a remaining difficulty would be on a source of 
human oocytes, both for research purposes, but also eventually for 
large-scale clinical implementation. We believe there may be certain 
advantages to the use of ``surrogate'' oocytes from animal sources. 
Animal oocytes could be supplied in large numbers on an economical 
basis, they could be ``humanized'' so as to provide fully human cells 
with human, rather than animal, mitochondria, and they could also 
potentially be engineered to be defective in producing a fetus even if 
used in an inappropriate effort to clone a human being by implantation 
in a uterus. Since these oocytes would be produced in cloned animals 
(presumably cows), they could, in principle, offer two advantages: (1) 
an economical and ethically acceptable source of oocytes for 
therapeutic cloning, and (2) it is possible that they could be 
engineered to be effective in dedifferentiating human cells and 
allowing differentiation into specific lineages, but defective in 
creating a human embryo if implanted into a uterus. This may prevent 
the abuse of the technology in the event of an inappropriate use of the 
technology in attempting to produce a pregnancy.
    The NT technologies described above are not designed to be used for 
the cloning of a human being. Advanced Cell Technology has no intent to 
clone a human being, and we are opposed to efforts to clone a human 
being. As of today, we see no clear utility in producing a child by NT, 
and even if such uses were identified, NT would likely carry with it an 
inappropriately high risks of embryonic and fetal wastage. However, we 
believe that the production of genetically-engineered surrogate animal 
oocytes may be an important resource for medical research, and may 
solve certain practical and ethical problems associated with sourcing 
human oocytes and the risks of abuse in human reproductive cloning.
    It should be emphasized that the above-mentioned technologies are 
still in the very earliest stages of development. It is not possible as 
of today to determine whether the production of human ES cells through 
sexual or asexual means will meet all the necessary requirements for 
the development of human therapeutics. What is clear however, is that a 
careful, informed, and reasoned public discourse would help insure that 
these technologies could develop to the point where they could be used 
in the clinic to treat human disease
                         ethical considerations
    The problem of sourcing human cells and tissues for transplantation 
raises numerous ethical dilemmas. Because developing embryonic and 
fetal cells and tissues are ``young'' and are still in the process of 
forming mature tissues, there has been considerable interest in 
obtaining these tissues for use in human medicine. However, the use of 
aborted embryo or fetal tissue raises numerous issues ranging from 
concerns over increasing the frequency of elected abortion, to simple 
issues of maintaining quality controls standards in this hypothetical 
industry. Similarly, obtaining cells and tissues from living donors or 
cadavers is also not without ethical issues. For instance, an important 
and largely unresolved issue is whether it is morally acceptable to 
keep ``deceased'' individuals on life support for long periods of time 
in order to harvest organs as they are needed.
    The implementation of ES-based technologies could address some of 
the ethical problems described above. First, it is important to note 
that the production of large numbers of human ES cells would not in 
itself cause these same concerns in accessing human embryonic or fetal 
tissue, since the resulting cells have the potential to be grown for 
very long periods of time. Using only a limited number of human embryos 
not used during in vitro fertilization procedures, biotechnology could 
theoretically supply the needs of many millions of patients if the 
problem of histocompatibility could be resolved. Second, in the case of 
NT procedures, the patient may be at lower risk of complications in 
transplant rejection. Third, the only human cells used would be from 
the patient. Theoretically, the need to access tissue from other human 
beings could be reduced.
    On March 4, 1997 President Clinton asked for a, ``moratorium on the 
cloning of human beings until our Bioethics Advisory Commission and our 
entire nation have had a real chance to understand and debate the 
profound ethical implications of the latest advances.'' Prior to this 
1997 request and the cloning of Dolly, Advanced Cell Technology had 
initiated research into the use of human somatic cell NT for human cell 
therapy (therapeutic cloning) and had obtained preliminary results that 
suggested the technology would be useful in treating disease. Following 
the President's request, however, the Company tabled all research in 
this area awaiting clarification of recommended guidelines. After 
internal review in 1998, the Company decided that it did not have 
sufficient data to assemble a scientific publication, but believed that 
it was in the public interest to release the preliminary results to 
promote an informed and reasoned public discussion of the issues. In 
this regard, we are grateful for the President's request of November 
14, 1998 asking the National Bioethics Advisory Commission to analyze 
the issues surrounding this new technology.
    In regard to the President's letter of November 14, 1998, we would 
like to offer the following observations. First, we share the 
President's concerns regarding the mixing of DNA across species. By way 
of background, it is useful to recall the debate surrounding the 
specter of mingling of human and non-human DNA in gene splicing 
technologies in the 1970s. In addition to the general discomfort of 
combining the genes of organisms across the plant and animal kingdoms, 
there were more focused concerns raised concerning the deliberate 
mixing of the genomes of viruses such as adenovirus and tumor viruses 
such as SV40 or between SV40 and bacteria such as E. coli for fear that 
new and virulent man-made pathogens may unintentionally result in a 
major health risk. Shortly thereafter, there were again concerns voiced 
over the mixing of antibiotic resistance genes in bacteria not then 
possessing such resistance. The resolution of those concerns may guide 
us in the consideration of these new technologies. The use of 
attenuated strains of host organism, and other precautions have served 
us well and allowed recombinant technology to advance and, in doing so, 
to improve the human condition.
    Concerns over the mixing of the genomes of differing species is 
even of greater concern given newer technologies that allow the 
transfer of entire chromosomes across species. Given justifiable 
concerns that these technologies not be abused in medical research, we 
join in asking for ethical debate of the issue of the mixing of genomic 
DNA across species.
    The mixing of DNA across species does not, however, bear on the 
issue of NT. The research performed in 1996 resulted in human cells 
with less than one millionth of the DNA being from a nonhuman (bovine) 
source, and that DNA was for the mitochondria, an energy source for the 
cell, not encoding species-specific traits such as eye color, 
intelligence, or other distinctive features. In addition, it was, and 
is, the intent of Advanced Cell Technology to produce fully-human stem 
cells through the genetic modification of the bovine egg cell to 
introduce human mitochondrial DNA.
    The relevant issue is that the biotechnology industry is seeking 
guidelines for the application of ES and NT technologies in medicine. 
We believe that these new technologies, if properly applied, could lead 
to significant medical advances with lifesaving potential. Poorly 
constructed legislation, designed to prohibit the cloning of a human 
being, could inadvertently interfere with urgent and ethical 
applications of the technologies in medicine.
    Prohibitions against humanized surrogate NT may also have serious 
collateral consequences in addition to harming these new therapeutic 
avenues. During various in vitro protocols, it is not unlikely that 
human oocytes or embryos may be cultured in the presence of bovine 
proteins, such as bovine fetal calf serum. It would be unwise to set a 
precedent that the contact of a human embryonic cell with nonhuman 
(bovine) proteins is to be prohibited. Proteins do not encode 
hereditary information. The sensitivity remains in the area of mixing 
genomes (DNA) of human and animal, likely not the mixing of proteins, 
especially in the surrogate protocol under discussion wherein the 
bovine proteins are rapidly replaced by human.
    We therefore respectfully request that Congress be measured and 
forward-thinking taking into full account the tools necessary for 
medical researchers to apply these exciting new technologies in 
clinical practice in the future.
[GRAPHIC] [TIFF OMITTED] T07DE02.003

                                 ______
                                 

                               Appendix A

michael david west, b.s., m.s., ph.d., curriculum vitae, september 1998
Personal
    Date and Place of Birth: April 28, 1953; Niles, Michigan.
    Citizenship: U.S.A.
    Ethnicity: Caucasian.
    Marital Status: Married, no children.
    Home Address: 555 Bryant St., No. 280, Palo Alto, CA 94301.
    Email: [email protected].
Education
    Niles Senior High School; Niles, MI: 1971.
    Rensselaer Polytechnic Institute; Troy, NY: B.S. Major: Psychology 
1976; Minor: Management.
    Andrews University; Berrien Springs, MI; M.S. Biology 1982.
    Baylor College of Medicine; Houston, TX: Ph.D. Cell Biology 1989, 
(Division of Molecular Virology)
Business Experience
    West Motor Leasing Company, Inc., President, General Manager, 1976-
1982.
    West Leasing Company, Inc., President, General Manager, 1978-1982.
    West Motor Sales, Inc., President, General Manager, 1980-1982.
    Geron Corporation, Founder, Director, Officer, 1990-1998.
    Origen Therapeutics, Inc., Founder, Chairman, 1997-Present.
    Advanced Cell Technology, Inc., President & CEO, 1998-Present.
Research and Professional Experience
    1998-Present: President and CEO, Advanced Cell Technology, Inc., 
One Innovation Dr., Worcester, MA 01605.
    1997-Present: Founder, Chairman, Origen Therapeutics, Inc., 651 
Gateway Blvd., Ste. 980, South San Francisco, CA 94080.
    1994-1998: Founder and V.P. of New Technologies, Geron Corporation, 
200 Constitution Dr., Menlo Park, CA 94025.
    1993-1994: Founder and V.P. of Business Development, Geron 
Corporation, 200 Constitution Dr., Menlo Park, CA 94025.
    1992-1993: Founder, VP, and Chief Scientific Officer, Geron 
Corporation, 200 Constitution Dr., Menlo Park, CA 94025.
    1990-1992: Founder, President and CEO, Geron Corporation, 200 
Constitution Dr., Menlo Park, CA 94025.
    1990-1992: Senior Research Scientist, Department of Cell Biology 
and Neuroscience, Southwestern Medical School, 5323 Harry Hines Blvd., 
Dallas, Texas 75235, Laboratories of: Dr. Woodring E. Wright, Dr. Jerry 
W. Shay.
    1989-1990: Postdoctoral Research Fellow, Department of Cell Biology 
and Neuroscience, Southwestern Medical School, 5323 Harry Hines Blvd., 
Dallas, Texas 75235, Laboratories of: Dr. Woodring E. Wright, Dr. Jerry 
W. Shay.
    1985-1988: Graduate Student (Ph.D.), Baylor College of Medicine, 
Division of Molecular Virology, One Baylor Plaza, Houston, TX 77030.
    1982-1985: Graduate Student (Doctoral Candidate), University of 
Arkansas for Medical Sciences, Department of Biochemistry, 4301 W. 
Markham, Little Rock, AR 72205.
    1979-1982: Graduate Student (M.S.), Andrews University, Department 
of Biology, Berrien Springs, MI 49104.
                                 ______
                                 

                              Bibliography

Patents
    1. West, M.D. 1996. Trypsin-sensitive Agent Able to Reduce PAI-1 
and beta-APP Expression in Senescent Cells and Increase the Ability of 
Fibroblasts to Divide in Culture. U.S. Patent No. 5,482,838.
    2. West, M.D., Shay, J., Wright, W. 1996. Therapy and Diagnosis of 
Conditions Related to Telomere Length and/or Telomerase Activity. U.S. 
Patent No. 5,489,508.
    3. West, M.D. 1996. PADPRP Inhibitors to Treat Diseases Associated 
with Cellular Senescence. U.S. Patent No. 5,589,483.
    4. Shay, J., West, M.D., and Wright, W.E. 1997. Methods for Cancer 
Diagnosis and Prognosis. U.S. Patent No. 5,639,613.
    5. West, M.D., Harley, C.B., Strahl, C.M., McEachern, M.J., Shay, 
J., Wright, W.E., Blackburn, E.H., and Vaziri, H. 1997. Therapy and 
Diagnosis of Conditions Related to Telomere Length and/or Telomerase 
Activity. U.S. Patent No. 5,645,986.
    6. West, M.D., Shay, J., and Wright, W.E. 1997. Telomerase 
Diagnostic Methods. U.S. Patent No. 5,648,215.
    7. West, M.D., Shay, J., and Wright, W.E. 1997. Methods for 
Screening for Agents which Modulate Telomere Length. U.S. Patent No. 
5,686,245.
    8. West, M.D., Shay, J., and Wright, W.E. 1997. Methods and 
Reagents for Lengthening Telomeres. U.S. Patent No. 5,686,306.
    9. Shay, J., West, M.D., and Wright, W.E. 1997. Methods for Cancer 
Diagnosis and Prognosis. U.S. Patent No. 5,693,474.
    10. West, M.D., Shay, J., Wright, W., Blackburn, E.H., and 
McEachern, M.J. 1997. Telomerase Activity Assays for Diagnosing 
Pathogenic Infections. U.S. Patent No. 5,695,932.
    11. West, M.D. 1998. Method to extend life span and proliferative 
capacity of cells--comprises administration of polyadenosine 
diphosphate-ribose polymerase inhibitor to cells. WO 9827975.
    12. Feng, J., Funk, W., Hirsch, K.S., Linskens, M.H.K., 
Villeponteau, B., and West, M.D. 1998. Identifying, isolating, and 
regulating senescence-related genes--useful to ameliorate problems 
associated with accumulation of senescent cells, e.g. age-related 
lipofuscin accumulation in the retina and AIDS. U.S. Patent No. 
5,744,300.
    13. Blackburn, E.H., Shay, J., West, M.D., and Wright, W. Therapy 
and Diagnosis of Conditions Related to Telomere Length and/or 
Telomerase Activity. Australian Patent No. 688.262.
    14. Linskens, M.H.K., Hirsch, K.S., Villeponteau, B., Feng, J., 
Funk, W., and West, M.D. 1998. Methods and Reagents for the 
Identification and Regulation of Senescence-Related Genes. U.S. Patent 
No. 5,744,300.
Scientific Publications
    1. West, M.D., Pereira-Smith, O.M., and Smith, J.R. 1989. 
Replicative Senescence of Human Skin Fibroblasts Correlates with a Loss 
of Regulation and Overexpression of Collagenase Activity. Experimental 
Cell Research, 184:138-147.
    2. West, M.D. 1989. An Examination of Growth Factor Modulation of 
Extracellular Matrix Metabolism in Human Skin Fibroblasts During 
Cellular Senescence In Vitro, Ph.D. Dissertation, Baylor College of 
Medicine, Houston, TX.
    3. Shay, J.W., West, M.D., Wright, W.E. 1992. Re-expression of 
Senescent Markers in De-induced Reversibly Immortalized Cells. Exp. 
Gerontology. 27:477-492.
    4. West, M.D. 1994. The Cellular and Molecular Biology of Skin 
Aging. Arch. Dermatol. 130:87-95.
    5. Harley, C.B., Kim, N.W., Prowse, K.R., Weinrich, S.L., Hirsch, 
K.S., West, M.D., Bacchetti, S., Hirte, H.W., Counter, C.M., Greider, 
C.W., Piatyszek, M.A., Wright, W.E., and Shay, J.W. 1994. Telomerase, 
Cell Immortality, and Cancer. Cold Spring Harbor Symposium on 
Quantitative Biology LIX: 307-315. Cold Spring Harbor Press. Cold 
Spring Harbor, N.Y.
    6. Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, 
M.D., Ho, P.L.C., Coviello, G.M., Wright, W.E., Weinrich, S.L., and 
Shay, J.W. 1994. Telomerase Activity is Associated with Cell 
Immortality and Advanced Human Carcinomas. Science, 266:2011-2014.
    7. Feng, J., Funk, W.D., Wang, S-S, Weinrich, S.L., Avilion, A.A., 
Chiu, C-P., Adams, R., Chang, E., Allsopp, R.C., Siyuan Le, J-Y., West, 
M.D., Harley, C.B., Andrews, W.H., Greider, C.W., Villeponteau, B.V. 
1995. The RNA Component of Human Telomerase. Science. 269:1236-1241.
    8. Linskens, M.H., Harley, C.B., West, M.D., Campisi, J., and 
Hayflick, L. 1995. Replicative Senescence and Cell Death. Science 
267:17.
    9. West, M.D. 1995. Chromosome and Breakage. In The Encyclopedia of 
Aging. 2nd Edition. Springer, NY. p179.
    10. West, M.D., Shay, J.W., Wright, W.E., and Linskens, M.H.K. 
1996. Altered expression of plasminogen activator and plasminogen 
activator inhibitor during cellular senescence. Exp. Gerontol. 31:175-
193.
    11. Effros, R.B., Allsopp, R., Chiu, C-P., Hausner, M.A., Hirji, 
K., Wang, L., Harley, C.B., Villeponteau, B., West, M.D., and Giorgi, 
J.V. 1996. Shortened telomeres in the expanded CD28- CD8+ cell subset 
in HIV disease implicate replicative senescence in HIV pathogenesis. 
AIDS 10:F17-F22.
    12. Vaziri, H., West, M.D., Allsopp, R.A., Davison, T.S., Wu, Y-S., 
Arrowsmith, C.H., Harley, C.B., Poirier, G.G., and Benchiol., S. 1997. 
ATM-dependent telomere loss in aging human diploid fibroblasts and DNA 
damage lead to the post-translational activation of p53 protein through 
poly (ADP-ribose) polymerase. EMBO J. 16:6018-6033.
    13. West, M. D., and Hjelmeland, L. M. 1997. Replicative 
senescence: A role in age-related macular degeneration? (Invited 
review, manuscript in preparation).
    14. West, M. D. 1997. Collagenase and Aging. In The Collagenases, 
Springer Verlag, In Press.
    15. Matsunaga, H., Handa, J.T., Aotaki-Keen, A., Sherwood, S. W., 
West, M.D., and Hjelmeland, L.M. 1998. Markers of Preplicative 
Senescence in Human Retinal Pigment Epithelial Cells in vitro. Invest. 
Ophthalmol. Vis. Sci. (In Press).
    16. West, M.D. Telomere Length Assays in Gerontological Research. 
1998. Invited Review, Manuscript in Preparation.

                             curing disease

    Senator Specter. Dr. Varmus, we will begin the first round 
of questioning with you. There has been considerable discussion 
already about curing disease, dealing with life-threatening 
ailments, Parkinson's, heart disease, cancer, Alzheimer's. Are 
there any limitations as to the range of this kind of a 
technique on curing diseases? Would it apply to everything?
    Dr. Varmus. Well, Senator, it is a little difficult to 
answer the question because it is very difficult to know what 
science would be capable of producing. As you have heard from 
the----
    Senator Specter. But the basic point is you find a way of 
replicating cells which are diseased. So would there be any 
apparent limitation on the scope of these technologies to cure 
any kind of a disease?
    Dr. Varmus. There would be certain kinds of diseases; for 
example, infections would not immediately be amenable to 
therapies with these cells. But as you have heard, one of the 
limitations that currently exists is that, while we know that 
the cells in question can form many different kinds of tissues, 
we do not yet have the knowledge that allows us to efficiently 
differentiate them into the tissue of choice.
    Moreover, as Dr. West just pointed out again and as others 
of us have alluded to, we do not yet have a clear solution to 
the problem of what we call histocompatibility, having tissues 
that can be delivered to any individual and not rejected by 
that individual's immune system. Indeed, the use of somatic 
cell nuclear transfer methods does offer promise in this regard 
and there is the potential for developing cell lines with 
pluripotent potential using that methodology.
    Indeed, in last year's discussion of the Human Cloning 
Prohibition Act the President issued a statement of 
administration policy in which he wanted to preserve the 
ability to use somatic cell nuclear transfer with human cells 
for the purpose of developing stem cells for exactly this 
purpose. Of course, we view there to be a prohibition on that 
kind of research at the moment due to the amendment that I 
alluded to in our appropriation bill.

                          parkinson's disease

    Senator Specter. Dr. Varmus, perhaps it would be helpful to 
take a specific ailment and to run through how this approach 
would, say, deal with Parkinson's. Could you use that 
illustratively to tell us what could be done to treat someone 
with Parkinson's?
    Dr. Varmus. As you know, Senator, Parkinson's is a result 
of loss of certain nerve cells in a region of the brain called 
the basal ganglia. Those cells are responsible for producing 
dopamine, an important neurotransmitter. There already are 
methodologies in use that attempt to restore brain function, 
for example by transplanting fetal cells to the brains of 
individuals with this disease, or by attempting to inactivate 
cells that usually inhibit the ability of other cells to 
produce dopamine.
    You saw, still can see, a picture of nerve cells derived in 
Dr. Gearhart's experiments from his pluripotent stem cells. One 
could imagine being able to induce cells that specifically make 
dopamine and to introduce those cells using so-called 
stereotaxic instrumentation into the appropriate place in the 
brain to restore the function of that part of the nervous 
system.
    Senator Specter. Well, how will the stem cell technique 
advance the current techniques used to deal with Parkinson's?
    Dr. Varmus. Well, the objective would be to be able to 
produce cells that are specifically designed to carry out the 
function of the cells that have undergone deterioration in the 
process of developing the disease. I cannot give you one, two, 
three yet, because obviously there is work to be done. But the 
point would be to have a large repertoire of cells that, rather 
than having to go and identify and having to use many fetal 
donors, essentially, one could have a bank of cells that is 
known to respond to certain kinds of chemical instructions to 
make the kinds of cells that would be useful in the 
transplantation process.
    Senator Specter. One of the questions which those of us on 
this side of the panel always ask with respect to time line and 
cures is how much appropriations will set you in motion to find 
the answer. But illustratively, is it possible to give a 
generalization, if this research were unleashed, how long it 
would take to find a cure, say to Parkinson's or Alzheimer's?
    Dr. Varmus. Well, remember, Senator, that I referred to the 
fact that certain kinds of stem cells are already in use in 
clinical practice, for example blood stem cells, and there are 
experimental models, especially in mice, that indicate that 
certain other tissues, like the heart, may be repaired by the 
use of cells that have been converted from committed stem cells 
to heart muscle cells using an appropriate recipe.
    Given those precedents, it seems to me that within the 
course of the next decade or two, with an appropriate cadre of 
investigators, that many, many diseases would be at least 
treated, if not entirely cured, by the kinds of cell therapies 
we are talking about.

                             use of embryos

    Senator Specter. My red light is on, but I am going to ask 
one final question of Dr. Thomson with respect to the embryos. 
There is the obvious concern of the use of embryos where an 
embryo could be the start of a human life. In your research in 
the use of embryos, how do you deal with this specific issue?
    Dr. Thomson. The embryos that we used were specifically 
made for clinical purposes, but they were beyond what the 
patients could use. The majority of these embryos had been 
frozen for a number of years and they had to decide what to do 
with them. The option that they were considering was to discard 
them, so it was a choice between discarding the embryos and 
doing this research.
    Senator Specter. So what you are saying is that none of the 
embryos which you used had the possibility of being the start 
of a human life?
    Dr. Thomson. Because they would otherwise be discarded, 
yes.
    Senator Specter. Because?
    Dr. Thomson. They would have otherwise been discarded.
    Senator Specter. Otherwise been discarded.
    Well, my time is up.
    Senator Harkin.

                federal ban on research on human embryos

    Senator Harkin. Mr. Chairman, thank you.
    Since we have a limited amount of time, I have two things I 
want to kind of clear up. One kind of gets to the heart of the 
matter, I hope, here on whether or not the use of these stem 
cells are covered under the Federal ban that was placed here a 
couple of years ago on research on human embryos. Now, let me 
just read the law. It says: ``None of the funds made available 
in this act may be used for: (1) the creation of a human embryo 
or embryos for research purposes.'' We're not talking about 
that here, is that clear? Is that right? ``(2) Research in 
which a human embryo or embryos are destroyed, discarded, or 
knowingly subjected to risk of injury or death greater than 
that allowed for research on fetuses in utero under pertinent 
sections of the Public Health Service Act.''
    Is that included here? ``None of the funds made available 
under this act may be used for research in which a human embryo 
or embryos are destroyed, discarded, or knowingly subjected to 
risk of injury or death greater than that allowed for research 
on fetuses in utero under 45 CFR,'' et cetera, et cetera.
    Now, let me read the next paragraph: ``B. For purposes of 
this section, the term' human embryo or embryos' includes any 
organism, not protected as a human subject under 45 CFR 46 as 
of the date of enactment of this act, that is derived by 
fertilization, parthenogenesis, cloning, or any other means 
from one or more human gametes or human diploid cells.''
    My point is this. It says: ``For purposes of this section, 
the term' human embryo or embryos' includes any organism.'' 
Now, I heard someone say that these stem cells are not 
organisms. Now, so I asked my staff to get me the dictionary. I 
want to find out what an ``organism'' is. In this dictionary, 
Random House--maybe it is different in some others--it says: 
``Organism. 1. A form of life composed of mutually dependent 
parts that maintain various vital processes.''
    Now, to my limited scientific knowledge, that definition 
does not meet a stem cell. It does not seem that a stem cell 
contains ``mutually dependent parts that maintain various vital 
processes.''
    So my question is, getting back to the matter of whether or 
not these are covered by the ban on Federal human embryo 
research: One, are these organisms? Are these stem cells 
organisms? I am just asking. Anybody? Dr. West?
    Dr. West. The cultured cells I would say are not. If they 
are, for instance, grown in a laboratory dish or transplanted 
into a uterus, they will not form a human being. They have 
never been observed to form a complete animal using the animal 
equivalent of these cells.
    Senator Harkin. Dr. Varmus.
    Dr. Varmus. As a scientist, as I have testified here today 
from the perspective that I bring to this from my professional 
background, I agree that these are not organisms. The issue 
that we are dealing with in the Government is complying with 
the law, knowing the legal definition of an organism, and we 
are struggling with this as part of the activities in the 
Department and elsewhere in the administration to be sure that 
any actions we take in response to these developments are in 
compliance with existing law.
    Senator Harkin. I understand.
    Dr. Thomson, are these organisms?
    Dr. Thomson. They are not organisms and they are not 
embryos.
    Senator Harkin. They are not organisms?
    Dr. Thomson. Or embryos, no.
    Senator Harkin. Or embryos.
    Dr. Gearhart. No; they are not. They are not organisms.
    Senator Harkin. They are not organisms.
    Well, I may not be a very good scientist, but I am somewhat 
of a lawyer and I do read the English language. It says: ``For 
the purposes of this section, the term `human embryo or 
embryos' includes any organism.'' If it is not an organism then 
it is not included.
    So that is why I made the statement that I did at the 
opening of this session. From my reading of it and my 
understanding of it, this is not covered by the Federal ban. If 
someone has a different definition of ``organism'' I would like 
to see it.
    Second, during the debate last year on human cloning the 
National Conference of Catholic Bishops cited a number of 
alternative ways to conduct research using stem cells, 
alternatives they said would not require the use of a human 
embryo at all. They include: (A) stimulating proliferation and 
differentiation of the quiescent stem cells which are known to 
exist in many adult tissues and customizing those cells to each 
individual patient; (B) collecting stem cells from bone marrow 
or umbilical cord blood or collecting stem cells from fetal 
bone marrow; (C) genetically engineering cells of different 
kinds to repair damaged organs, perhaps by injecting them with 
an oncogene.
    Do any of you know of this research? Is it possible to 
achieve the same therapies with these alternatives? I am not a 
scientist. I do not understand this.
    Dr. Varmus. Senator, in my testimony I alluded to the fact 
that there was a tremendous amount of research already 
supported by the NIH and by private industry and many other 
countries on stem cells that exist in fetal and adult tissue 
that has the potential to develop into specific types of cells. 
We think this is very important research. Indeed, it has 
produced many of the advances in transplantation of bone marrow 
and reconstitution of bone marrow that is used daily in 
hospitals. So we strongly endorse that approach.
    What is at issue, though, is the tremendous potential for 
working with cells that are earlier in that hierarchy of stem 
cells that I described to you earlier. Certain fundamental 
questions about how cells differentiate, how we become complex 
organisms, how birth defects arise, what causes cancer, how 
cells fail, tools for use in development of new 
pharmaceuticals, the ability to expand the repertoire of cells 
that can be used for tissue therapies, is in my view going to 
have to be approached with cells that come from organisms 
earlier in development.
    Now, as I have also tried to indicate, research with such 
cells does create ethical concerns and we need to address those 
and balance those against the benefits.
    Senator Harkin. I understand. I think what is important 
here is that when I read the news accounts and the newspaper 
stories they say stem cells as if every stem cell is exactly 
the same.
    Dr. Varmus. That is wrong.
    Senator Harkin. That is wrong. We have to clear that up 
here today for the public. When you are talking about stem 
cells you are talking about a broad spectrum of stem cells.
    Dr. Varmus. That is correct.
    Senator Harkin. Yes?
    Dr. West. We call them stem cells maybe in part because it 
is a bit like a tree. The stem cells we are talking about today 
are at the base of the development tree and can branch out into 
all the different cells and tissues of the body. Some stem 
cells are way out at the edges of the branches and can only 
become a few different cell types. There are many cell types. 
There are tissues in the body that have no stem cells.
    Heart tissue, the leading cause of death in the United 
States, there are no stem cells to repopulate the heart. They 
simply do not exist. But, going back to the base of the 
developmental tree, we believe we can potentially make heart 
muscle cells that can be used to address the No. 1 cause of 
mortality.
    Senator Harkin. I thought that was important to clarify.
    Thank you.

               treating age-related degenerative diseases

    Senator Specter. Thank you, Senator Harkin.
    We are going to take another round here and try to hold it 
just to the five and five, because we do have quite an array of 
other witnesses.
    Dr. West, you used the phrase that the technique would make 
cells young and would certainly be a retarding of the aging 
factor. Just how far could this go? Do we really have what 
could be a realistic fountain of youth by the use of this 
technique?
    Dr. West. I think a fountain of youth may be a bit of a 
stretch. But what we do have published information on is that 
the process of nuclear transfer does impart back to an aged 
cell the full proliferative capacity it had when it was born. 
Dolly, after all, was born as a young lamb, not an old one.
    Senator Specter. So what are the limitations which would 
stop it from being a veritable fountain of youth?
    Dr. West. I am excited about the possibilities of using 
somatic cell nuclear transfer to treat age-related degenerative 
disease. There is now growing evidence that in numerous 
diseases associated with aging that there are cells that have 
lost the potential to proliferate in the way that they did when 
they were young, and so nuclear transfer could be used to treat 
immunosenescence, the aging of our immune system. The elderly 
increasingly find it difficult to fight infectious disease, 
chronic pneumonias, and other things.
    So the nuclear transfer has the potential to benefit 
embryonic stem cell research in personalizing these cells--they 
are genetically identical to you--eliminating actually many 
ethical problems associated with sourcing cells and tissues 
today. As you know, the FDA is reviewing possibilities of 
making cells and tissues in animals, xenografts, taking pig 
kidneys and pig heart valves and so on, and sourcing cells and 
tissues from cadavers, keeping people alive to source cells and 
tissues.

                                cloning

    Senator Specter. Dr. West, let me just interrupt you, if I 
might, because we have very limited time, and ask you this one 
other question. Your company's technique has been characterized 
as the use of cloning techniques to create an embryo out of 
human and cow cells. Is that accurate with respect to the 
characterization of cloning?
    Dr. West. I think it is very inaccurate. Actually, the 
cartoons that show the half-human, half-cow I think are science 
fiction. The goal here is to use the proteins in the egg after 
the genomic information is removed to reprogram a human cell.
    Senator Specter. When you use the human and cow cells, 
eyebrows are raised. What concerns do you have about the 
joinder of human and cow cells?
    Dr. West. I actually agree with the President's letter of 
November 14, where he asked the National Bioethics Advisory 
Commission to look into this issue of the mixing of species. It 
has been a profound debate for years in the scientific 
community. As you know, the recombinant DNA debate of the 
1970's was a debate about the mixing of DNA across species, and 
this is even more profound today. We have the ability today to 
actually introduce whole chromosomes across species, not single 
genes.

                          Parkinson's disease

    Senator Specter. Dr. Gearhart, what kind of a time line do 
you see on the kind of research you have done to provide 
practical answers to problems like Parkinson's or Alzheimer's 
or cancer?
    Dr. Gearhart. Actually, I think Parkinson's will be one of 
the first targets and one that we will see in a short period.
    Senator Specter. How long is a short period?
    Dr. Gearhart. Well now, let me back off.
    Senator Specter. No, no; go on.
    Dr. Gearhart. I will. I actually think within several 
years, to be honest with you, because these neurons that I have 
demonstrated here, we do not know, to be honest, since this is 
new data, we do not know what neurons they represent, what 
type, whether they are cholinergic, dopaminergic, etcetera.
    But from what we have known from our colleagues' work who 
are studying the differentiation of neurons in animals, the 
dopaminergic neurons are one of the first ones that are 
developed. We know more, I think, about what factors actually 
result or will lead to the formation of a dopaminergic neuron.
    Senator Specter. Dr. Gearhart, I want to get a fairly short 
answer from doctor--did you want to say something?
    Dr. Gearhart. I should have explained dopaminergic neuron, 
which is the neuron that is deficient in Parkinson's.
    Senator Specter. I want to get a brief answer from Dr. 
Thomson and Dr. West on time line for practical application 
before the red light goes on.
    Dr. Thomson. There are practical applications even today, 
not in therapeutics right away. But for example, for making 
heart muscle cells, there are very simple techniques to do this 
in mouse embryonic stem cells and they will probably transfer 
fairly quickly to human embryonic stem cells.
    Senator Specter. Applicable today?
    Dr. Thomson. Applicable today, because you can use them for 
drug screens.
    Senator Specter. Illustratively, for Parkinson's how long?
    Dr. Thomson. Parkinson's? I am going to say 5 to 10 years 
more. It will be one of the first ones.
    Senator Specter. Dr. West, what time line do you see?
    Dr. West. I would estimate for the discovery of drugs, 
using the cells simply to discover drugs in the laboratory, 3 
to 5 years; for the first cell therapies, somewhere between 7 
to 15 and 20 years; Parkinson's potentially beginning within 7 
to 12 years.
    Senator Specter. Thank you.
    Senator Harkin.
    Senator Harkin. That is very encouraging. What I hear you 
saying is that if this basic research is allowed to go forward 
that a minimal amount of understanding of how stem cells 
develop will lead to a proliferation of knowledge, which then 
can be used by a lot of scientists all over the field. Is that 
sort of--am I thinking the right way?
    Yet, if you block this basic understanding of how that stem 
cell differentiates, that means that all those scientists out 
there cannot then focus on how to apply it in that timeframe. 
Am I close to it? Something like that?
    So that is why I am grateful the chairman has called this 
hearing, because of the misinformation I think is out there, 
especially regarding the ES technologies, and the 
misinformation as to whether or not this is really covered by 
the law banning human embryo research.
    Let me focus a little bit--now, you talked about this time 
line that the chairman just laid down in terms of Parkinson's. 
What I heard was that anywhere from 3 to 5 to 12 years, 
somewhere in there we might be finding something. Is that 
assuming the Federal ban continues and this research is not 
allowed to go forward, or that it is federally funded and 
only--hold on I need to back up.
    You can do this research in the private field. NIH cannot 
fund it. What I heard all of you say is that it would be 
vitally important, to have NIH be able to fund it. If this 
Federal ban is deemed to cover research on stem cells, does 
your time line hold?
    Dr. West. The time line I gave, 7 to 12 years for 
Parkinson's, assumed that the NIH would be allowed to fund 
research in differentiating these cells into cells for 
Parkinson's.
    Senator Harkin. So your answers were based on----
    Dr. West. Yes.
    Senator Harkin [continuing]. I should not say lifting the 
ban because, you see, I do not think the ban applies.
    Dr. West. Right.
    Senator Harkin. So I have got to be careful about what I 
say. So your time line is based upon an interpretation or 
reading of this that the ban does not apply to stem cells?
    Dr. West. Right.
    Senator Harkin. Is that true of all of you?
    Dr. Varmus. That is correct.
    Dr. Thomson. That is correct, but also the number of 
diseases likely to be treated by this will increase 
exponentially if there is public funding. Industry can target 
one or two or a couple and get it done in a reasonable time. 
The more difficult ones will just be left undone.

                                diabetes

    Senator Harkin. So you are saying, again, with this 
research there could be all kinds of breakthroughs later.
    Dr. Thomson. Take diabetes as an example. Take diabetes as 
an example. That is caused by the death of a very particular 
cell in the pancreas and it is a fairly difficult developmental 
program to go from undifferentiated stem cell to beta islet 
cell. That is likely to be a more difficult cell to derive from 
embryonic stem cell. It requires a lot of basic research, and 
the Government has the job of doing basic research.
    Senator Harkin. Well, I think there is so much potential 
here. But there is so much misinformation out there, the 
cartoons of the half-horse and the half-human, going back to 
Greek mythology. I think we have been burdened with Greek 
mythology for far too long. [Laughter.]
    Senator Harkin [continuing]. And we have to get past that.
    But our job I think as legislators--and again I compliment 
the chairman; I thank him for having this hearing--is to try to 
get over these hurdles of misinformation that are out there. 
And I can understand people having these fears based upon 
inadequate knowledge and understanding of what you are doing.
    I think our job is to make sure that we get that 
understanding out there in a clear fashion.
    So I compliment you all for the work you are doing. I 
believe that if this research is allowed to go forward it is 
the gateway to a lot more understanding of how we treat 
illnesses, especially genetic illnesses. Now, how the proper 
way is, whether it is NT-based, nuclear transfer-based, or the 
ES-based, I do not know. That is way above my pay grade. But I 
think in either case the Federal ban certainly does not apply.
    I thank you for your work and I encourage you to press on, 
and hopefully we will have a clearing up of this so that NIH, 
Dr. Varmus, can move ahead very aggressively in this area. I 
would close on that question: If, in fact, this is the case, 
will NIH move ahead aggressively?
    Dr. Varmus. We will certainly do so, with, of course, the 
usual oversight. That is, we will have a panel, we will have 
guidelines, we will have the review of grant applications, and 
proceed as we did on previous topics, like recombinant DNA or 
gene therapy and xenotransplantation, with due consideration of 
the ethical issues and firm oversight of the science.
    Senator Harkin. Thank you, Dr. Varmus.
    Senator Specter. Thank you very much for your testimony, 
gentlemen. I think that it has been very useful in shedding 
light on the issue that the embryos which are used here are not 
embryos which could produce life, that when we talk about fetal 
tissue, as Dr. Gearhart has talked about it, it is discarded 
fetal tissue, it is not related to any inducement of abortions 
or any medical procedure to produce fetal tissue.
    Dr. Gearhart. That is correct.
    Senator Specter. But there is concern, as Dr. West has 
described, for the cloning consideration and for the mixture of 
cows and human cells, and, perhaps most importantly, the 
projection as to when immediate practical application may be 
present. Dr. Thomson points out that with certain heart cells 
it is now.
    It is obviously a heart-rendering situation to see people 
with Alzheimer's. We just had a very difficult situation in a 
Veterans Administration hospital in Coatsville, PA, where 
people with Alzheimer's, veterans, who could not walk were 
being excluded from treatment. We finally got that solved. 
People with Parkinson's had a major event in Pittsburgh last 
year with Muhamed Ali coming forward and people with the 
Parkinson's ailment. One man has an hour glass that he measures 
his time by.
    And as we work through juvenile diabetes, and this 
subcommittee is deluged with people who want more funding and 
more answers and more responses to their medical problems. We 
did the maximum last year with $2 billion. Senator Harkin and I 
do not know what we can do for an encore this year.
    But when you talk about medical research which may provide 
very, very unique answers with all the people who are suffering 
there, we want to see what the medical potential is. It appears 
to be very, very promising for catastrophic illnesses.
    We are now about to turn to a panel to deal with the 
ethical considerations, the other side of the coin. So we very 
much appreciate your coming, and now we will call panel two.
    Senator Harkin. I am sorry, there is one other point I just 
have to clear up. Could I just clear up one thing?
    Senator Specter. One final question.
    Senator Harkin. I have to clear up something. I want to ask 
you a question. I am drafting a letter of my own to Dr. 
Shapiro, but the letter that the President wrote said: ``I am 
deeply troubled by this news of experiments involving the 
mingling of human and nonhuman species.''
    What you are saying, Dr. West, is that that is not 
scientifically correct?
    Dr. West. Well, I share his concern about the mingling of 
genomic DNA. That is not what we are doing.
    Senator Harkin. That is right. I would share that concern, 
too, combining genomic DNA. I would share that, too. But you 
are saying that that is not happening?
    Dr. West. That is not what we are doing.
    Senator Harkin. I just wanted to clear that up.
    Dr. Varmus. We also want to focus on the question of 
whether experiments are being conducted in cultured cells as 
opposed to experiments that would involve any attempt to return 
a potential embryonic cell to a womb to develop a mature 
individual. That is a very important distinction that was 
repeatedly made by my embryo research panel when they 
considered these experimental approaches.
    Senator Harkin. Thank you very much.
    Thank you, Mr. Chairman.
    Senator Specter. Thank you very much, gentlemen.
STATEMENT OF ARTHUR L. CAPLAN, Ph.D., DIRECTOR, CENTER 
            FOR BIOETHICS, UNIVERSITY OF PENNSYLVANIA
    Senator Specter. We would now like to call Dr. Caplan, Dr. 
Doerflinger, Dr. Okarma; and we are going to bring Dr. Meslin 
in on the next panel, all together.
    Our first witness is Dr. Arthur Caplan, first witness on 
the second panel, who is director of the Center for Bioethics 
at the University of Pennsylvania, had that position since 
1994; also serves as the chairman of the advisory committee to 
the Department of Health and Human Services Centers for Disease 
Control and Food and Drug Administration on Blood Safety and 
Availability. Ph.D., from Columbia, author of some 400 articles 
in professional journals.
    Welcome, Dr. Caplan. The 5-minute rule is in effect and the 
floor is yours.
    Dr. Caplan. Thank you, Senator.
    I have to say, too, that you have made the people at the 
legislative liaison office at the University of Pennsylvania 
very happy with your announcement about staying on this 
committee. They will be more interested in that than anything I 
have to say here.
    When I left this morning I was trying to look at some 
books, as philosophers such as myself are wont to do, about 
ethical ideas. I did look a little bit at the Greek myths. I am 
not as skeptical as Senator Harkin that Greek mythology is 
useless, since to some extent the Greeks kept going with great 
zeal in trying to advance what we call science today, though 
they tried to warn us about not being full of hubris and pride 
when we did it.
    I looked at some other ethics books on my shelf, but I 
realized that the real source of my knowledge about what is 
right and wrong is to ask my 14-year-old son. So I sat him down 
and I said: Now, I am going down to Washington. The issue is, 
if we try hard to respect human origins and try hard to respect 
human embryos and try hard to understand the special nature of 
procreation, if we have a technology that offers us benefits, 
that might help the paralyzed, the disabled, people dying of 
heart disease and other dread ailments, how do you think we 
should trade this off?
    My son said, ``Well, dad, it seems to me if you have got a 
man in a wheelchair you owe that person something in the here 
and now, as opposed to trying hard to respect what might be or 
what could have been, what is potential.''
    I think he is right. I think it is true that the goal of 
our public policy should be to tell that person in a wheelchair 
we are going to try and weigh tradeoffs morally, ethically, 
between the hard choices that have to be made in using certain 
tissues, certain cells as sources, dealing with certain 
totipotent and pluripotent cells as points of origin for making 
wondrous therapies, and that it is wrong in the end if we 
cannot come up with a policy that says we will not hold that 
person in a wheelchair hostage to our moral concerns about 
tissues that will otherwise be destroyed, tissues that are not 
going to be turned into human beings under any circumstances, 
or cells and tissues that, because we misunderstand or 
misdescribe them, are going to wind up being misclassified as 
potential people or possible human beings.
    We have heard about that in the first panel and I think 
that is the goal that faces Congress and the executive branch, 
is to try and get us into the right balance.
    The other introductory thing I would like to say is just 
that I find myself as a philosopher, someone interested in 
ethics, amazed by these developments this past year, 2 years, 
ranging from cloning and creation of origin cells, oocytes from 
animals that might be places where animal sources can be used 
to host the production of human proteins, and stem cell 
developments.
    It reminds me that we do not live in a world of moral 
absolutes. Some of the bright lines that we think we can go to 
are not so bright when the DNA of any cell can be converted 
ultimately, potentially, to a human being by transfer and 
technology that allows for nuclear cell cloning. We can no 
longer say that we understand exactly when life begins, how to 
respect life, depending upon certain properties that might 
inhere in particular cells or tissues.
    It seems to me in the end that what we have got to do is 
this. We have to say that some principles ought guide us as we 
move forward in this area, and I want to propose four, and I 
think they are ones that guide all medical research.
    The first is that we should seek to achieve the most good 
or benefit with the least harm and destruction of things that 
we value. I believe that we do value human procreation, human 
origins, human embryos, and we want to try and minimize what we 
have to do there to get benefit, but we must pursue benefit.
    That tradeoffs to achieve progress in the struggle against 
disease and disability are inevitable and they are ethical. We 
do that every day, Senators, when we conduct human research and 
understand that we put people at risk, that deaths will result 
from some of the things that are tried, that we may hasten 
death inadvertently. We understand that tradeoffs must be made, 
and I think that applies in this area.
    It seems to me that the creation of materials with the 
capacity to become human life is a process that requires moral 
guidance and humility. That is something that I think we are 
going to have to inject in this debate.
    The last principle I would like to advance is that it is 
better to do things in this area that are accountable and 
public than it is to ask them to become private and commercial. 
If we continue the policies we have, we are not going to be 
able to bring the nuanced supervision and oversight that this 
area of stem cell research requires from us.

                           prepared statement

    I want to end by saying again, I do not think we are in the 
realm of absolutes. I think we need judgment. I think we need 
virtues. That is why we need public funding, public 
accountability, to make the right tradeoffs.
    Senator Specter. Thank you very much, Dr. Caplan.
    [The statement follows:]

                 Prepared Statement of Arthur L. Caplan

                 the ethics of human stem cell research
Why is stem cell research so important?
    Tremendous fanfare has greeted the announcement of success in 
identifying human embryonic stem cells. Fanfare is becoming an 
increasingly common phenomenon in the world of science and biomedical 
news. So there is a tendency to greet each weeks `breakthrough' with 
some cynicism. But in the case of the isolation of pluripotent 
embryonic stem cells the acclaim is surely merited.
    The identification of human embryonic stem cells has been widely 
acknowledged as of inestimable value because it will help scientists 
understand basic mechanisms of embryo development and gene regulation. 
It also holds the promise of allowing the development of techniques for 
manipulating, growing and cloning these cells to permit the creation of 
designer cells and tissues. The availability of immortal stem cell 
lines will greatly aid drug discovery. The study of stem cells should 
also shed light on the process of human fertility and growth and should 
even open the door to techniques that could be used, someday, to permit 
many forms of genetic engineering and transplant therapy for human 
beings.
    There are many in the biomedical community who, when confronting 
such powerful and useful possibilities maintain that no steps or 
actions should be taken to restrict, control much less prohibit this 
important research from moving forward. There is even the suggestion 
that anyone who raises questions about the ethics of human embryo stem 
cell research is merely using the prospect of research in this area for 
``political'' purposes.
    Such objections are rhetorically powerful but not at all 
persuasive. As many scientists, policy makers, religious leaders and 
the American people have long understood, research that may lead to the 
elucidation of the secrets of human reproduction and development, the 
modification of the genetic makeup of future children and their 
children, the creation of new forms of life and a bounty of therapies 
that hold out the prospect of a longer and better life raises issues of 
ethics and social policy that must be discussed and debated publicly. 
It is very appropriate that these issues be raised and examined since 
human embryonic stem cell research is in its infancy and there is still 
time to shape and direct its course.
    Ironically, the much of the work being done on human embryonic stem 
cells is being done without the support of funding from American 
governmental agencies. This is entirely due to ethical concerns about 
any research involving human embryos and tissues derived from elective 
abortions. Embryonic stem cell research has and may involve these 
sources.
    Many worry that to raise any questions about the ethics of stem 
cell research is to sacrifice a crucially important and incalculably 
valuable area of biomedical research on the alter of the abortion 
controversy. They also despair that any dialogue can occur in our 
society about the ethics of using materials derived or created from 
embryonic sources given the horrid track record of social divisiveness 
and violence that are the constant companions of any discussion of 
abortion in this country,
    But the reality is that unless some effort is made to address head 
on the moral and social issues that embryo stem cell research raises it 
is very likely that further advances in this area will be slowed as a 
result of a lack of government support or because they will be 
conducted completely under private auspices with little accountability 
and relatively little accessibility to the community of biomedical 
science. The value of embryonic stem cell research is simply too great 
to permit a policy stance of inaction to be the response that our 
government and other governments around the world offer to this 
enormously promising domain of inquiry.
            key ethical issues raised by stem cell research.
Sources
    The most obvious and pressing issue raised by stem cell research is 
the issue of the source of these cells. Stem cells can be obtained from 
human embryos specially created for research purposes, they can be 
obtained from aborted fetal tissues including both spontaneous and 
elective abortions, they can be created by processes that involve the 
transfer of genetic materials to either animal or human egg or embryo 
hosts and they can be obtained from embryos created through various 
means of artificial reproduction and then frozen either as no longer 
wanted by the persons whose gametes created them, or, being held as 
reserves for the future by couples seeking to have children. What is 
fascinating about these many sources of human embryonic stem cells from 
an ethical point of view is that they are not at all morally 
equivalent.
Not all embryos are created equally
            Specially created embryos
    The moral problems with making embryos for research are that as a 
society we do not want to see embryos treated as products or mere 
objects for fear that we will cheapen the value of parenting, risk the 
commercialization of procreation, and trivialize the act of 
procreation. It is the moral framework that society wishes to construct 
for procreation and reproduction, and the interests of those whose 
gametes are involved in making embryos, that provide much of the moral 
force for restricting or prohibiting the manufacture of embryos for 
nonprocreative uses. This is especially so once it is realized that 
most human embryos at the point of conception will not become human 
beings even under the best of all possible developmental circumstances. 
Those who study the problem of infertility are beginning to understand 
what it is about certain eggs and embryos that make them unlikely or 
unable to develop into fetuses and later babies. While it is true as a 
matter of historical fact that all human life has begun with conception 
it is not true that all conception is capable of becoming human life. 
Nor will it be true for long that all human life must begin with 
conception. These changing realities mean that much more fine-tuned and 
nuanced conceptual framework is needed to keep pace with advances in 
knowledge and manipulability of human gametes and embryos.
    The moral problems with making embryos for research are that as a 
society we do not want to see embryos treated as products or mere 
objects for fear that we will cheapen the value of parenting, risk the 
commercialization of procreation, and trivialize the act of 
procreation. Society may or may not agree that a human conceptus is 
deserving of full ethical standing and respect on a par with an adult 
human being. But, surely we do have a broad consensus in American 
society that the process of creating embryos that have the potential 
and ability to become human beings requires special status and standing 
within our law and our culture.
    If that is so then the manufacture of embryos for stem cell 
research will have the potential to become persons may be morally 
suspect because it violates our desire to accord special standing and 
status to human conception, procreation and sexuality. To do nothing in 
this area it should be noted is to consign the practice of embryo 
creation for generating stem cells to the marketplace which is to 
completely abrogate any special standing or status to human conception 
and procreation.
            Spare embryos
    One of the greatest ironies of current policies governing embryo 
research in the United States is that it has created a situation in 
which a huge industry has arisen to treat infertility with relatively 
little oversight and accountability for its practices. It has also 
created a situation in which the demand for clinical services is high 
but the knowledge base of those providing techniques such as in vitro 
fertilization (IVF) is not what it might be because of the lack of 
Federal funds to support fundamental research. As a result, when 
couples seek to use IVF they are required to create more embryos than 
they or their doctors might wish in order to minimize the need to 
create more should they fail to have a child and to help insure that at 
least some embryos will be made that are capable of growth and 
development. This means that some fortunate couples are lucky enough to 
have the technique work on a first or second try but wind up with the 
problem of what to do with remaining surplus or spare embryos. This 
country now finds itself in a situation in which tens of thousands of 
orphan embryos sit in liquid nitrogen unwanted and highly unlikely to 
be used by anyone ever to try to make babies.
    Recently the United Kingdom enacted legislation to permit the 
destruction of unclaimed and unwanted embryos. The United States has 
not done so but there are thousands of embryos that might be made 
available for research and study for many purposes including stem cell 
research if those who created them were given this option or if clinics 
could make them available for this purpose after a waiting period of 
say ten years.
    There are some who would still object that these frozen embryos are 
still potential persons. But that claim does not square with the facts. 
If no woman is willing to have the embryos placed inside her bodies, if 
clinics are reluctant to use embryos that have been stored for long 
periods of time because their potential to become babies is diminished 
or if couples do not want anyone else using their embryos then their 
potential for becoming persons is zero.
    There would be a moral problem if embryos were created solely for 
the purpose of being frozen and then used for research. Such a practice 
would demean human reproduction and sexuality in turning it into a 
process of manufacture and mass production. But, it is very simple to 
prevent such practices from occurring. If infertility clinic personnel 
understood that it was illegal and punishable by fine and prison to 
inquire if a couple or woman wanted to freeze embryos until an IVF 
cycle had been completed, then there would be no incentive to create 
embryos. Spare, unwanted or damaged embryos could then be made 
available for stem cell research, storage with consent or future 
utilization.
    To those who say this is still permitting the use of human embryos 
for a purpose that is disrespectful, research and the consequent 
destruction of the embryo, it seems appropriate to ask why continued 
freezing is not just as disrespectful. It is also appropriate to ask 
why, even if regrettable and sad, it would not be worth permitting the 
donation of spare embryos for research that might lead to cures and 
benefits in much the same way that we allow families to donate their 
loved ones organs and tissues under the most tragic of circumstances to 
aid others? Spare embryos would seem to be a legitimate and morally 
defensible source of human embryonic stem cells.
            Constructions
    Perhaps the most disturbing source of stem cells is from embryos 
that are specially built or designed for this purpose. Chimeras, human-
animal mixtures believed capable of prolonged development from 
conception, possibly to birth, fused cells using enucleating human or 
animal eggs and genomic transfer, disabled oocytes or embryos made from 
disabled sperm are but a number of possible ways in which scientists 
might create new forms of embryos to generate embryonic stem cells. The 
ethically positive side of this kind of construction is that it may be 
possible to create useful stem cells without having to use embryos that 
have any potential to become persons. The negative side is that the 
creation of special embryonic constructs may involve the creation of 
potential whose outcome is uncertain, unknown or would have the 
potential to create a severely deformed and damaged living organism. 
The complexities in this area require a nuanced moral response but it 
does seem clear that a clear boundary line must be to prohibit the 
creation of any living being that would with certain become or have the 
potential to become a deformed, damaged, freakish or dying entity. 
There are also other risk involved with some forms of construction that 
take human genomic material into animal hosts or vice versa. These 
include the danger of importing viral matter or sub-viral entities into 
the human population. There are also risk that some material may then 
be carried into stem cells made from such sources.
       some possible moral principles to guide stem cell research
    It might be helpful once it is recognized that there are no hard 
and fast lines to be drawn with respect to the ethics of stem cell 
research to try and advance some simple moral principles that might 
help those charged with controlling or approving such research. I would 
suggest the following as principles which are in evidence already in 
other areas of biomedical research and therapy:
  --Seek to achieve the most good or benefit with the Least harm and 
        destruction of things of value
  --Tradeoffs to achieve progress in the struggle against disease and 
        disability are both inevitable and ethical
  --The creation of materials with the capacity to become human life is 
        a process that requires moral guidance and humility.
  --The complexity of the tradeoffs involved when research is being 
        conducted at the boundaries of human life requires 
        accountability and publicity.
    Each of these principles is used to justify activity in biomedical 
research and therapy that is known to be risky or even known to be 
harmful but which has important benefits to individuals and society. 
Our society is quite familiar with the concept of tradeoffs. Americans 
recognize few moral absolutes and in the area of stem cell research 
where the tradeoffs frequently involve the possibility of harm to 
potential persons versus the reality of harm to real flesh and blood 
persons it is hard not to use some of these principles to guide prudent 
choices, albeit tragic ones. To be blunt it would be hard to honor 
principles such as these and the role they play in biomedicine and many 
areas of public life and still tell the persons paralyzed in a 
wheelchair or immobile as a consequence of ALS or Muscular Dystrophy or 
Parkinson's that they must remain in such states because of inviolate 
moral concern for the moral standing of an unwanted frozen embryo.
               public versus privately sponsored research
    Perhaps the most neglected factor in weighing what to do with 
respect to stem cell research is the reality that stem cell research 
will proceed even without federal funding. It will proceed more slowly 
but it will proceed. It will proceed with no accountability but it will 
proceed. It will proceed cloaked in secrecy but it will proceed. And it 
will proceed with an eye toward the commercially attractive rather then 
basic knowledge or the public good but it will proceed. The importance 
of the benefits to be garnered in this area makes it imperative that 
speed, accountability, publicity, and the drive to understand shape as 
much of the early course of stem cell research as is possible. Add to 
this the fact that the world of embryo sources and the status of stem 
cells themselves is complex and it becomes certain that it would be 
better to see publicly sponsored research complement private activities 
and publicly accountable oversight accompany the market ethos that soon 
will prevail in the United States if no action is taken by government.
  a brief history of policy response to the ethics of embryo research
    Announced with great fanfare, the Acting Director of NIH 
established a panel to recommend guidelines for the funding of 
preimplantation embryo research in August 1993. The Human Embryo 
Research Panel was composed of 19 members, including 11 researchers, 
scientists and physicians, 4 ethicists, 2 lawyers and 2 public members. 
It met in public six times from February to September 1994, when it 
issued its final report. The panel's charge was to place potential 
research involving the ex utero preimplantation human embryos into one 
of three categories: (1) acceptable for federal funding; (2) warrant 
additional review; and (3) unacceptable for federal funding.
    Using the mechanism of majority vote, the panel concluded that 
studies to improve chances of pregnancy; research on fertilization; 
research on egg activation, maturation and freezing; preimplantation 
genetic diagnosis; development of embryonic stem cells; and creation of 
parthenotes were acceptable for federal funding. Unacceptable research 
included cloning and use of fetal oocytes followed by transfer to a 
female uterus, and cross-species fertilization. This panel's 
recommendations have been more or less ignored by the NIH Director, 
Congress and the President ever since.
    The reason why is that the moral foundation for the panel's 
recommendations about embryo research was not persuasive. Unless a 
moral framework emerges that proponents and critics of embryo research 
can accept, it is likely that policy recommendations about stem cell 
research will meet the same fate. This ought not be allowed to happen 
since the scientific, therapeutic and commercial benefits of stem cell 
research are too enormous to reject or hinder simply as a result of an 
inability to confront a tough ethical problem head on.
   why was the moral framework used to support some embryo research 
                            unsatisfactory?
    The panel considered and rejected the moral stance that a human 
embryo has rights that would completely prohibit its use in research. 
To those who argue that an embryo is a human person from the moment of 
conception, the panel responded that there is no single trait or 
property present at conception that suffices to confer personhood, and 
thus, rights, on an embryo.
    Having rejected rights as the proper framework for thinking about 
the moral status of the human embryo, the panel recommended the 
adoption of what it termed ``a pluralistic approach.'' Embryos possess 
``a variety of distinct, intersecting and mutually supporting 
considerations such as ``genetic uniqueness, potentiality for full 
development, sentience, brain activity, and degree of cognitive 
development''. The panel argued that ``their developing presence in an 
entity increases its moral status until, at some point, full and equal 
protectability is required.'' In essence the panel recommended a `big 
tent' solution.
    But, the pluralistic framework was not and is not persuasive. Just 
saying embryos have a lot of potential and many different emerging 
properties leaves matters mysterious and unresolved. It is not clear 
what properties of embryos confer moral standing or worth and which are 
simply properties that are interesting but irrelevant to ethics. 
Without more of an underlying rationale for why particular property or 
set of properties are morally important, the panel's framework wound up 
looking like it was constructed to rationalize a desired conclusion--
that some research on embryos ought to be permitted--rather than as a 
conclusion which follows from an ethical analysis.
    The failure to be persuasive about the moral status of the embryo 
turned out to be a crucial failure of the report. Saying that embryos 
have a combination of properties which somehow entitle them to respect 
without explaining how those properties confer moral significance on 
embryos or what it means to say an embryo ought to be treated with 
respect leaves policy makers and ultimately biomedical scientists with 
little to work with in terms of moral guidance.
    What the earlier panel which took on the analysis of the ethics of 
embryo research did not grasp is that the human embryo has moral 
standing not so much for what it is at the moment of conception, but 
because the embryo is the result of procreative activity which is 
intended to produce or is at least capable of producing a child. This 
means that for many embryos there are other human beings who have a 
direct interest in the status and fate of the human embryo since their 
gametes created it, it carries their genes and potentially could become 
their child. It also means that the key moral characteristics of human 
embryos are not their inherent properties but the potential that they 
have to become persons and the intent that those who created them have 
to permit those which can do so to do so.
    The same analysis is true but only more so for human embryonic stem 
cells. Some of these cells come from embryos which had the capacity to 
become persons. Some may be located and studied in embryos that lack 
any such capability. Some stem cells will originate in embryos which 
have no prospect of becoming persons because they are slated for 
immediate destruction. And still other stem cells might originate in 
embryos which were intentionally created so as to lack the ability to 
become a person under any circumstances. To simply ban all stem cell 
research as immoral because it relies on human embryos of some sort as 
the source of such cells is to conflate what are fundamentally 
different embryos with different moral standing. And to equate stem 
cells themselves with human embryos capable of becoming persons is to 
commit the same conceptual mistake but only in a more flagrant form.
    In order to understand what is and is not ethical with respect to 
stem cell research it is necessary to know a great deal about the 
nature of the human embryo where such cells must be identified and 
isolated, something about the stem cells themselves, something about 
the aims and goals of the research and something about the benefits 
that are likely to eventuate from a particular research study. Simple 
moral schemes of classification are not sufficient for negotiating this 
dense biological terrain. It will take a committee or commission with 
the time and expertise to review particular proposals from specific 
researchers to make the judgements that are required.
                          what should be done?
    I conclude with three recommendations based on my understanding of 
the nature of the issues raised by stem cell research and the 
complexity of ethical and social questions such research raises:
    1. America needs to create a public forum where advances in biology 
and genetics can be discussed by ethicists, philosophers, theologians 
and other humanists and social thinkers so as to permit a richer set of 
concepts and categories to emerge so as to enhance public and political 
understanding of what it is to talk of the creation of human life, new 
forms of life and potential life.
    2. America needs to seek to allow the many benefits of stem cell 
research to be secured. This does not however make moral discussion of 
how to proceed simply political. Nor does it mean that concerns and 
worries about the moral licitness of stem cell and embryo research must 
always yield to the promise of benefits and new knowledge.
    3. America needs to create an oversight body, committee or 
commission with appropriate expertise to consider and approve requests 
for research protocols involving stem cell and embryo research.
STATEMENT OF RICHARD M. DOERFLINGER, ASSOCIATE DIRECTOR 
            FOR POLICY DEVELOPMENT, SECRETARIAT FOR 
            PRO-LIFE ACTIVITIES, NATIONAL CONFERENCE OF 
            CATHOLIC BISHOPS
    Senator Specter. Our next witness is Mr. Richard 
Doerflinger, associate director for policy development for the 
secretariat for pro-life activities, National Conference of 
Catholic Bishops. During Mr. Doerflinger's 18 years of service 
he has been responsible for the preparation of policy 
statements and congressional testimony on a wide variety of 
subjects, including abortion, euthanasia, reproductive 
technologies, and other medical and moral issues for the 
Bishops Conference. Master of arts in divinity from the 
University of Chicago, widely published on ethical issues 
relating to the dignity of human life.
    Thank you for joining us, Mr. Doerflinger, and the floor is 
yours.
    Mr. Doerflinger. Thank you very much, Mr. Chairman.
    I would ask that my longer statement be entered into the 
record and I will summarize it briefly.
    Senator Specter. The full statement will be made a part of 
the record, as will all others, and you have the 5 minutes for 
summarizing or as you choose.
    Mr. Doerflinger. I think it is important in assessing these 
experiments to know that when Congress decides to subsidize 
various forms of human experimentation it is making a moral and 
not just an economic decision. It is deciding that these are 
kinds of research that are sufficiently valuable and also 
sufficiently ethical to be done in the name of all Americans 
and all American taxpayers. By making those funding decisions, 
Government can make an important moral statement, set an 
example for private research, and help direct research toward 
avenues which are ethically appropriate as well as medically 
useful.
    Three kinds of experiments involving human embryos have 
been discussed here. On one level, some of these experiments 
advance the debate on human cloning in ways that I think are 
interesting and productive, because they indicate that there 
are ways of making useful stem cells other than the use of 
human somatic cell nuclear transfer of cloning, and that in 
fact human cloning could be banned without endangering such 
research. There would be other avenues available.
    At the same time, however, each of the experiments 
discussed raise ethical and, yes, legal questions of its own. 
Currently the drive for advances in fetal and embryonic 
research are balanced against ethical considerations in three 
different areas of law, the law on life fetal research which 
has been in existence since 1975, which treats the embryo and 
fetus, at least from the time of implantation, as a protectable 
human subject that must be protected from harmful research.
    I say that with emphasis because a number of people here 
have talked about whether this kind of embryo or that is 
capable of creating a human being, and we saw pictures of 
little bouncing babies over here. But in the area of law we are 
talking about, a human being, a human subject worthy of 
protection, includes the human embryo.
    There are also, of course, appropriations riders since 1995 
which extend this to the pre-implantation human embryo, not 
only to special creation of embryos for research purposes, but 
also to harmful or destructive research on embryos already in 
existence.
    Finally, we have fetal tissue transplantation guidelines 
which we, it will be no surprise to you, find inadequate 
because we do not think that tissues should be obtained from 
abortion victims at all. But those guidelines as well have some 
guidelines on how any use of tissue, even from a dead fetus, 
should be separated as much as possible from any decisions to 
destroy that fetus, that the destruction should not be geared 
toward the research or the timing and manner of it should not 
be geared toward the use of the tissue.
    Along those lines, I find that two of the three experiments 
that have been discussed here are exactly the kind of thing 
that the human embryo research ban was directed against. Dr. 
West's experiment, with all due respect, does involve a use of 
cloning to create human embryos, which are then harvested for 
their stem cells and thus destroyed.
    The fact is that the reason for using nuclear transfer here 
is to produce a genetic match for each individual patient. So 
for each individual patient who may need treatment, you would 
need to be making some number of new human embryos and then 
harvesting them for their tissues. This is a violation of both 
provisions of the current human embryo research ban. It creates 
embryos and then it destroys them.
    The research from the University of Wisconsin also involves 
destroying embryos, though it does not involve creating them 
because it gets them from IVF clinics. Again, that violates the 
embryo research ban.
    I think the more interesting question is whether subsequent 
use of the stem cells that have now been produced by that 
tissue would be violating the Federal ban. I think there we 
would have to look for precedent to the current fetal tissue 
transplantation guidelines, which say that the tissue should 
not be used if the manner of the destruction of the original 
fetus or embryo was geared toward or related to the research. 
It has to be done for unrelated reasons. it cannot be linked 
with the research.
    It seems to me that the way in which these cells are 
obtained, thus destroying the original embryo, is very much 
geared toward the banking of those tissues, and it raises an 
ethical problem that I think is parallel to the question that 
was already resolved by Congress with its guidelines on fetal 
tissue transplants.
    Finally, in conclusion, I think it would be sad if 
Congress' attention were to focus chiefly on those avenues of 
research which garner front page news precisely because they 
are ethically problematic. Congress has an opportunity to use 
its funding power to advance medical research in ways that 
fully respect human life as well as promoting medical progress.

                           prepared statement

    I believe that some of the aspects of Dr. Gearhart's 
research are very intriguing in this regard. We would like to 
explore it further, especially if the tissue that can be 
obtained can be obtained from sources other than abortion 
victims, because it does not seem, though there is some 
ambiguity here, that that research does not involve creating 
embryos which are then destroyed for cells.
    Thank you very much for allowing me to testify.
    Senator Specter. Mr. Doerflinger, we appreciate your being 
with us and thank you.
    [The statement follows:]

              Prepared Statement of Richard M. Doerflinger

    I am Richard M. Doerflinger, Associate Director for Policy 
Development at the Secretariat for Pro-Life Activities, National 
Conference of Catholic Bishops. I am grateful for the opportunity to 
present the Catholic bishops' ethical concerns regarding new 
developments in embryo research.
    In discussions of human experimentation, the researcher's 
temptation is to think that if something technically can be done it 
ethically should be done--particularly if it may lead to medical 
benefits or advances in scientific knowledge. A civilized society will 
appreciate the possibilities opened up by research, but will insist 
that scientific progress must not come at the expense of human dignity. 
When this important balance is not maintained, abuses such as the 
Tuskegee syphilis study or the Cold War radiation experiments become a 
reality.
    In deciding whether to subsidize various forms of human 
experimentation, legislators are not merely making an economic decision 
to allocate limited funds. On behalf of all citizens who pay taxes, 
they are making a moral decision. They are declaring that certain kinds 
of research are sufficiently valuable and ethically upright to be 
conducted in the name of all Americans--and that other kinds are not. 
By such funding decisions, government can make an important moral 
statement, set an example for private research, and help direct 
research toward avenues which fully respect human life and dignity as 
they seek to help humanity.
    Three kinds of experiments involving human embryos or embryonic 
cells have recently come to public attention. On one level, some of 
these experiments advance the ethical and legal debate on human 
cloning. They indicate that cloning is not necessary for promising stem 
cell research, and thus that it may be banned without endangering such 
research. At the same time, however, each of these experiments raises 
ethical problems of its own.
    Currently, the drive for advances in human fetal and embryonic 
research is balanced against ethical considerations in three 
significant areas of federal law. It is important to review these to 
address the question: What moral principles are reflected in these 
enactments that can help us to make a moral judgment on new experiments 
that may not have been anticipated before?
    1. Live fetal research is governed by federal regulations on the 
protection of human subjects first issued in 1975 (now codified at 45 
CFR Sec. 46.101 et seq.). Federal regulations on fetal research treat 
the prenatal human being as a human subject worthy of protection, from 
the time of implantation in the womb (about one week after 
fertilization) until a child emerges from the womb and is found to be 
viable. Essentially the same standard is applied here as in regulations 
protecting live-born children: Since the unborn child is a helpless 
subject incapable of giving informed consent to experimentation, 
federally funded research involving this child is permissible only if 
(a) it could be therapeutic for that particular child (as with prenatal 
surgery to correct congenital defects), or (b) it is necessary to 
obtain important information and will not subject the child to 
significant risk of harm.\1\ In 1985 Congress further clarified this 
standard through an amendment to the National Institutes of Health 
reauthorization act: In assessing research on live fetuses in utero, 
protection from risk must be ``the same for fetuses which are intended 
to be aborted and fetuses which are intended to be carried to term'' 
(42 USC Sec. 289g). No matter what fate may be planned for the 
developing human being by others, the government must still make its 
own moral decision to respect life--it cannot single out certain lives 
as disposable, or as uniquely fit for harmful research, simply because 
someone else plans to show disrespect for those lives.
---------------------------------------------------------------------------
    \1\ 45 CFR 46.208(a). Such research may only pose a ``minimal 
risk,'' which means that ``the probability and magnitude of harm or 
discomfort anticipated in the research are not greater in and of 
themselves than those ordinarily encountered in daily life or during 
the performance of routine physical or psychological examinations or 
tests.'' 45 CFR Sec. 46.102(i).
---------------------------------------------------------------------------
    2. Embryo research involving human embryos outside the womb--such 
as embryos produced in the laboratory by in vitro fertilization (IVF) 
or cloning--has never received federal funding. Originally this was 
because the federal regulations of 1975 prevented funding of IVF 
experiments unless such experiments were deemed acceptable by an Ethics 
Advisory Board--and after the first such board produced inconclusive 
results in 1979, no Administration chose to appoint a new board. In 
1994, after this regulation was rescinded by Congress, a Human Embryo 
Research Panel recommended to the National Institutes of Health that 
certain kinds of harmful nontherapeutic experiments on human embryos 
receive federal funding--but the Panel's recommendations were rejected 
in part by President Clinton, then rejected in their entirety by 
Congress. Since 1995, three successive Labor/HHS appropriations bills 
have prevented federal funding of experiments which involve (a) 
creating human embryos for research purposes, or (b) subjecting human 
embryos in the laboratory to risk of harm or death not permitted for 
fetuses in utero under the regulations on protecting human subjects. 
Since 1997 this rider has explicitly banned funding of experiments 
involving embryos produced by cloning using human body cells.\2\
---------------------------------------------------------------------------
    \2\ The current funding ban is Section 511 of the Labor/HHS 
appropriations bill for fiscal year 1999, enacted as part of Public Law 
105-277, the Omnibus Consolidated and Emergency Supplemental 
Appropriations Act for fiscal year 1999 (p. 399).
---------------------------------------------------------------------------
    3. Fetal tissue transplantation research has been a matter of 
extended controversy. Such research could receive federal funds during 
the Bush Administration only if the tissue was obtained from sources 
other than induced abortion. The possible use of ovaries from aborted 
fetuses to create research embryos provoked more controversy within the 
NIH Human Embryo Research Panel than perhaps any other proposal; in the 
end the Panel decided to defer any possible funding of such research 
until further discussion could take place. Under current federal 
funding policy, human fetal tissue--defined as ``tissue or cells 
obtained from a dead human embryo or fetus after a spontaneous or 
induced abortion, or after a stillbirth,'' (42 U.S.C. Sec. 289g-1(g))--
may be used for ``therapeutic purposes'' only if various safeguards are 
followed to ensure that the researcher avoids participating in an 
abortion and has no effect on the ``timing, method, or procedures used 
to terminate the pregnancy'' (42 USC Sec. 289g-1(b)(2)).
    In our view, current safeguards on the use of fetal tissue are 
inadequate. The only sure way to prevent federally funded research from 
collaborating in and providing legitimacy for abortion is to forbid 
abortion as a source for potentially ``therapeutic'' tissue. Certainly, 
it would be wrong for Congress to apply to early human embryos any 
policy less protective than that now applied to the later embryo and 
fetus. Existing law explicitly applies to human embryos, and destroying 
or discarding an embryo in the laboratory is the moral equivalent of 
abortion. As Congress has already done in the case of live fetal 
research, it should make clear in this area of research that the same 
standards apply to human embryos whether inside or outside the womb.
    Current law on live fetal and embryonic research is no mere 
political compromise. It is a reflection of universally accepted 
ethical principles governing experiments on human subjects--principles 
reflected as well in the Nuremberg Code, the World Medical 
Association's Declaration of Helsinki and other statements. Members of 
the human species who cannot give informed consent for research should 
not be the subjects of an experiment unless they personally may benefit 
from it, or the experiment carries no significant risk of harming them. 
Only by such ethical principles do we prevent treating people as 
things--as mere means to obtaining knowledge or benefits for others.
    Some will be surprised that such protections can exist under the 
U.S. Supreme Court's abortion decisions. But the Court has never said 
that government may not protect prenatal life outside the abortion 
context. It has even allowed states to declare that human life begins 
at conception, and that it deserves legal protection from that point 
onward--so long as this principle is not used to place an undue burden 
on a woman's ``right'' to choose abortion before viability.\3\ Although 
states may not place meaningful restrictions or prohibitions on 
abortion under current Supreme Court jurisprudence, harmful experiments 
on human embryos are illegal in ten states regardless of how they are 
funded.\4\ Public sentiment also seems even more opposed to public 
funding of such experiments than to funding of abortion.\5\
---------------------------------------------------------------------------
    \3\ Webster v. Reproductive Health Services, 492 U.S. 490 (1989).
    \4\ See testimony and documentation provided by Lori Andrews, J.D., 
to the NIH Human Embryo Research Panel, February 3, 1994. Ms. Andrews 
cites ten states whose laws on fetal research generally prohibit 
experiments on human embryos ex utero: Louisiana, Maine, Massachusetts, 
Michigan (which in 1997 also enacted a ban on creating human embryos by 
cloning), Minnesota, New Hampshire, North Dakota, Pennsylvania, Rhode 
Island and Utah.
    \5\ A national Tarrance poll in 1995 showed 18 percent support for 
using tax dollars for experiments that would involve destroying or 
discarding live human embryos in the first two weeks of development. 
Seventy-four percent of the Americans in the survey opposed such 
funding, with 64 percent strongly opposed. Press release, ``Poll Shows 
Strong Opposition to Embryo Research Funding,'' United States Catholic 
Conference, July 25, 1995.
---------------------------------------------------------------------------
    Moreover, a scientific consensus now recognizes the status of the 
early human embryo, and the continuity of human development from the 
one-celled stage onward, to a greater extent than was true even a few 
years ago. In the 1970s and 1980s, some embryologists spoke of the 
human embryo in its first week or two of development as a ``pre-
embryo'' and claimed it deserved less respect than embryos of later 
stages. But most embryology textbooks have now dropped the term, and 
some texts openly refer to it as a ``discarded'' and ``inaccurate'' 
term.\6\ The Human Embryo Research Panel and the National Bioethics 
Advisory Commission have both rejected the term; they describe the 
human embryo, including the one-celled zygote, as a living organism and 
``a developing form of human life.'' \7\
---------------------------------------------------------------------------
    \6\ See Ronan O'Rahilly and Fabiola Muller, ``Human Embryology and 
Teratology,'' 2nd edition (New York: Wiley-Liss 1996) at 8, 12. 
Professor Lee Silver of Princeton University, a proponent of cloning 
and embryo research, recently declared that the term ``pre-embryo'' was 
embraced by IVF researchers ``for reasons that are political, not 
scientific'' in an effort to ``allay moral concerns'' about their 
research. Lee M. Silver, ``Remaking Eden: Cloning and Beyond in a Brave 
New World'' (New York: Avon Books 1997), 39.
    \7\ See: National Bioethics Advisory Commission, ``Cloning Human 
Beings'' (June 1997), appendix-2 (``embryo'' as ``the developing 
organism from the time of fertilization''); National Institutes of 
Health, ``Report of the Human Embryo Research Panel'' (September 1994), 
at 2 (``the preimplantation human embryo warrants serious moral 
consideration as a developing form of human life'').
---------------------------------------------------------------------------
    How is this human life treated in each of the three most recent 
developments in human embryo research?
         university of wisconsin: stem cells from an ivf embryo
    The University of Wisconsin proposal seems to be exactly the kind 
of experiment that the federal funding ban was consciously directed 
against. Researchers obtained 36 live human embryos from IVF clinics, 
grew them to the blastocyst stage, and then destroyed them for their 
stem cells; cells from 14 of the embryos were placed in culture, and 
``cell clusters'' from five were successfully cultured to grow tissue. 
The researchers report that the inner cells were ``isolated by 
immunosurgery'' from the rest of the embryo.\8\ The effect is the same 
as if one were to ``isolate'' the heart and lungs from an adult human--
the being from whom the cells are taken is killed.
---------------------------------------------------------------------------
    \8\ James A. Thomson et al., ``Embryonic Stem Cell Lines Derived 
from Human Blastocysts,'' 282 Science 1145-7 (6 November 1998) at 1147 
n. 6.
---------------------------------------------------------------------------
    This kind of experiment was recommended for federal funding in 1994 
by the Human Embryo Research Panel, but rejected by Congress every year 
from 1995 to the present. In this respect it does not present a new 
issue, for Congress has already decided that even so-called ``spare'' 
embryos from IVF clinics should not be subjected to destructive 
experiments using federal funds.\9\
---------------------------------------------------------------------------
    \9\ On July 11, 1996, an amendment was offered by Rep. Nita Lowey 
(D-NY) to drop the ban on funding research involving ``spare'' embryos, 
while retaining the ban on special creation of ``research embryos''; 
the amendment was defeated 256-to-167.
---------------------------------------------------------------------------
    Two new issues have been raised regarding this experiment, however.
    First, could the embryonic cells that are removed from these human 
embryos, once isolated, be seen as human embryos themselves? The 
question arises because these inner cells are often described as the 
cells that would ultimately form the ``embryo proper'' as development 
continues. If removed from the original embryo but transferred to the 
nurturing environment of the womb, would each cell or each cluster of 
cells begin to develop as a new organism? Is a special environment 
provided by researchers to suppress such development and divert it 
toward undifferentiated growth as tissue instead? Certainly such 
diversion of embryonic development by use of molecular signals has been 
proposed by some researchers.\10\ If that were at work here--if the 
experiment creates new embryos and then suppresses their development--
funding such an experiment might also violate the current ban on 
creating human embryos for research purposes.
---------------------------------------------------------------------------
    \10\ See Lee M. Silver, supra note 6, at 128 (such molecular 
signals can be used as a way of ``tricking'' an early embryo into 
expanding as undifferentiated tissue, instead of undergoing normal 
growth and differentiation as an organism).
---------------------------------------------------------------------------
    Second, what of the prospect of funding research that would use 
this tissue for supposedly therapeutic purposes after it has been grown 
in culture? Here, the ethical principles reflected in current law on 
fetal tissue argue against funding the research. One must refer here to 
the principles rather than to the exact letter of the law because, 
while it applies to embryos as well as fetuses, it speaks of induced 
abortion rather than of destroying embryos by dissection. But there 
seems to be no reason why the same ethical standard should not apply. 
Human embryos are destroyed precisely to obtain this tissue, and the 
timing and manner of the destruction are tailored to obtaining this 
kind of tissue. An effective separation between the destructive act and 
the harvesting of the tissue, which federal law requires in the case of 
tissue from an induced abortion, does not seem to exist here.
    One positive development, however, is that this line of research 
has put to rest the claim made last year by some biotechnology 
companies that production of human embryos by cloning (somatic cell 
nuclear transfer) is necessary to develop therapies based on embryonic 
stem cells. Such claims assumed that adults could not be treated with 
such cells unless the embryos were produced by cloning to create a 
genetic ``match'' and avoid tissue rejection. But in his commentary on 
the Wisconsin experiment, John Gearhart has cited three other avenues, 
some of which were also cited by the National Bioethics Advisory 
Commission last year: Stem cells can be banked from multiple cell lines 
to prevent such reactions; they can be genetically altered to produce a 
universal donor line; or they can be customized using the relevant 
histocompatibility genes from the intended recipient.\11\
---------------------------------------------------------------------------
    \11\ John Gearhart, ``New Potential for Human Embryonic Stem 
Cells,'' 282 Science 1061-2 (6 November 1998) at 1061.
---------------------------------------------------------------------------
    Whatever else may be said of this research, then, it means that 
proposed federal bans on human cloning need no longer be held hostage 
to the debate on stem cell research. But the experiment itself is 
unethical and should not be funded. Instead, as the National Bioethics 
Advisory Commission has already observed,\12\ avenues should be 
explored for creating stem cell lines without creating or destroying 
human embryos.
---------------------------------------------------------------------------
    \12\ National Bioethics Advisory Commission, supra note 7, at 30-
31. See NCCB Secretariat for Pro-Life Activities, ``Would a Ban on 
Human Cloning Block Stem Cell Research?'' (Fact sheet, 4/20/98; 
www.nccbuscc.org/prolife/issues/bioethic/fact498.htm).
---------------------------------------------------------------------------
 johns hopkins: stem cells based on primordial germ cells from induced 
                                abortion
    Presumably the Johns Hopkins University study could not be funded 
unless it follows the provisions of current law regarding fetal tissue 
from induced abortions. We wish to reiterate here that we find the 
existing policy inadequate and would support federal funding only if 
the cells can be obtained from sources other than induced abortion.
    The new question raised here is this: Are the primordial germ cells 
obtained from abortion victims being used to create human embryos, 
which are then destroyed or suppressed to provide tissue. Even the NIH 
Human Embryo Research Panel did not recommend funding such an 
experiment, and it would clearly be forbidden by the current embryo 
research ban.
    There is some ambiguity in current reports of the new research, 
because the researchers speak of collecting ``embryoid bodies'' from 
these cultures and finding ``derivatives of all three embryonic germ 
layers'' in the culture. They add that some of these bodies form 
``complex structures closely resembling an embryo during early 
development,'' and that they ``appear to recapitulate the normal 
developmental processes of early embryonic stages and promote the cell-
cell interaction required for cell differentiation.'' \13\
---------------------------------------------------------------------------
    \13\ Michael J. Shamblott, et al., ``Derivation of pluripotent stem 
cells from cultured human primordial germ cells,'' 95 Proceedings of 
the National Academy of Sciences 13726-13731 (November 1998) at 13726, 
13729.
---------------------------------------------------------------------------
    However, if this research is now conducted--or could be conducted--
to establish useful cell lines without creating early human embryos, it 
would avoid some of the serious ethical problems associated with other 
experiments in this field. In that case the only remaining ethical 
problem is the use of cells from induced abortion, which does not seem 
necessary to the nature of the research. We urge that the use of cells 
from spontaneous abortions, ectopic pregnancies or other sources be 
explored instead.\14\
---------------------------------------------------------------------------
    \14\ See Peter J. Cataldo and Albert S. Moraczewski, O.P. (eds.), 
``The Fetal Tissue Issue: Medical and Ethical Aspects'' (Braintree, MA: 
Pope John Center 1994).
---------------------------------------------------------------------------
        advanced cell technology: human cloning using cows' eggs
    While this third type of experiment has not been fully reported in 
the medical literature it seems to pose a relatively new question--that 
of human/animal hybrids--as well as an old one, that of somatic cell 
nuclear transfer (cloning) to make human embryos for research purposes. 
Even the Human Embryo Research Panel opposed funding the former; the 
current ban on embryo research rightly forbids funding the latter.
    The National Bioethics Advisory Commission, in its November 20 
letter to President Clinton commenting on this experiment, rightly 
draws attention to the special ethical problems raised by combining 
human and animal cells to initiate embryonic development. On the one 
hand, this experiment does not create a hybrid in the sense of a being 
that is half human and half cow. All the nuclear genetic material comes 
from a human body cell; the cow egg contains some mitochondrial DNA, 
but this seems to be quickly taken over and directed by the human 
nucleus. On the other hand, proteins from the cow egg must be directing 
the remodeling of the chromosomes and thus the very earliest stages of 
development in this new being, and the ultimate effect of this is not 
known.
    However, even if this experiment in one sense does not create a 
human/animal hybrid, it presents a new twist on the use of cloning to 
create human embryos for research purposes. Oddly, defenders of such an 
experiment must simultaneously argue that it is promising because it 
can produce genetically matched, fully human tissue for 
transplantation--and that it is not covered by the ban on embryo 
research because fusing a human nucleus and a cow egg does not really 
produce a human embryo.
    Cows' eggs are apparently being used not to make hybrids as such, 
but to avoid one of the remaining practical obstacles to unlimited mass 
production of identical human embryos by cloning: the fact that human 
eggs are difficult to obtain in large numbers, and cannot be harvested 
in quantity without posing health dangers to women. Therefore this 
experiment not only poses ethical problems in its own right but could 
set the stage for further mistreatment of human life as an object of 
experimentation on a large scale. Funding for such an experiment should 
be, and is, banned by current law, which forbids creating a new 
organism from ``one or more'' human gametes or body cells by 
fertilization or cloning.
    In its new letter the Commission seems very uncertain as to whether 
this experiment creates an embryo. But this is partly due to the 
Commission's own truncated approach to what constitutes an embryo. Its 
assumption seems to be that the new being is an embryo only if it can 
be proved capable of growing and developing into a new ``human being,'' 
by which it means a live-born infant. But this is too narrow a 
standard. In many circumstances--especially those involving laboratory 
manipulation of new life--embryos are created in such a fatally damaged 
condition that they will not survive to live birth. This does not mean 
that they were never embryos. One might as well say that an infant born 
with a fatal disease, who will not survive to adulthood, was never an 
infant. This strange standard seems to grow out of the Commission's 
earlier attempts to propose that no ``human cloning'' has taken place 
so long as any human embryos created by cloning are ultimately 
discarded or aborted instead of being implanted to attempt a live 
birth.\15\ We believe the relevant question here is whether the new 
one-celled entity with a human nucleus begins, even for a brief time, 
to grow and develop as an early organism of the human species. If so, 
the experiment should be seen as involving the creation and destruction 
of human embryos and, as such, should not be funded.
---------------------------------------------------------------------------
    \15\ For a critique of this approach see Testimony of Cardinal 
William Keeler before the House Commerce Subcommittee on Health and 
Environment, February 12, 1998; reprinted in 27 Origins 597-601 
(February 26, 1998).
---------------------------------------------------------------------------
    Each of these new developments poses ethical questions, and none 
should be pursued by the federal government unless and until ethical 
questions have been satisfactorily answered.
    A remaining question involves the other avenues for advancing stem 
cell research, or for advancing the medical goals to which this 
research is directed, without exploiting developing human beings. Last 
year, for example, we proposed to Congress that there may be nine 
promising alternatives to the use of cloning to provide stem cell 
lines--and eight of these seem to involve no use of embryonic stem 
cells at all.\16\ In the same few weeks that these embryo experiments 
garnered such national attention, significant advances were reported in 
two of these areas: The use of growth factors to help hearts grow new 
replacement blood vessels, and the use of stem cells from placental 
blood to treat leukemia and other illnesses.\17\
---------------------------------------------------------------------------
    \16\ See NCCB Secretariat for Pro-Life Activities, supra note 12.
    \17\ See: ``Gene Therapy Helps Mice Grow New Blood Vessels,'' 
Business Wire, November 20, 1998; ``Injected Genes Help Grow Heart 
Bypasses,'' Washington Post, November 10, 1998 at A3; ``Stem Cells 
`Grow' in Value: Potential Benefits of Umbilical Cord Banking Further 
Validated,'' PRNewswire, November 27, 1998; Pablo Rubinstein et al., 
``Outcomes among 562 Recipients of Placental-Blood Transplants from 
Unrelated Donors,'' 339 New England Journal of Medicine 1565-77 
(November 26, 1998); Robertson Parkman, ``The Future of Placental-Blood 
Transplantation,'' 339 New England Journal of Medicine 1628-9 (November 
26, 1998). In light of some researchers' zeal for use of cloning by 
nuclear transfer to ensure an exact genetic match between tissue and 
recipient, it is worth noting that placental blood transplants seem to 
be more effective in treating leukemia if they are not too close a 
genetic match. Rubinstein et al. at 1573.
---------------------------------------------------------------------------
    It would be sad indeed if Congress's attention were to focus 
chiefly on those avenues of research which garner front-page news 
precisely because they are ethically problematic. Instead, Congress has 
an opportunity to use its funding power to channel medical research in 
ways which fully respect human life while advancing human progress. 
None of the new proposed experiments change in any way the ethical 
principle grounding current restrictions on human embryo research: In 
trying to serve humanity we should not support actions that are 
fundamentally wrong. Even a good end does not justify an evil means.
                                 ______
                                 

         Would A Ban on Human Cloning Block Stem Cell Research?

    Some biotechnology companies claim that a ban on producing human 
embryos through cloning would stall important research in generating 
``stem cells'' to cure a variety of diseases [Cong. Record, 2/5/98, 
S425]. To put this claim in perspective:
    1. Cloning is desired as a source of ``customized stem cell lines'' 
which would be an exact genetic match to each individual patient with a 
given disease. But this would require each individual patient to 
undergo somatic cell nuclear transfer to produce one or many living 
human embryos who genetically are the patient's identical twin sisters 
or brothers. These embryos would then be destroyed to provide embryonic 
stem cells.
    Two methods of obtaining the cells have been described. In one, the 
embryo is allowed to develop normally for a week or two to the 
blastocyst stage, at or after the usual time of implantation in the 
mother's womb; then this embryo, consisting of hundreds of cells, is 
dissected for its stem cells. The other method is to introduce 
molecular signals into the embryo's environment to ``trick'' its cells 
into departing from normal development and instead producing ``a mass 
of undifferentiated tissue,'' which can then be reprogrammed into 
various kinds of cells [Lee Silver, ``Remaking Eden: Cloning and Beyond 
in a Brave New World'' (Avon Books 1997), p. 128]. In either case, the 
living embryo is destroyed.
    2. This avenue for providing medical benefits has been described 
even by supporters as ``largely conjectural'' (J. Kassirer and N. 
Rosenthal, in ``New England Journal of Medicine,'' March 26, 1998, p. 
905). President Clinton's National Bioethics Advisory Commission called 
it ``a rather expensive and far-fetched scenario.'' The Commission 
observed: ``Because of ethical and moral concerns raised by the use of 
embryos for research purposes it would be far more desirable to explore 
the direct use of human cells of adult origin to produce specialized 
cells or tissues for transplantation into patients.''
    The Commission outlined three alternative avenues for promising 
research using stem cells that do not involve human cloning, two of 
which do not use human embryos at all (``Cloning Human Beings: Report 
and Recommendations of the National Bioethics Advisory Commission,'' 
June 1997, pp. 30-31).
                     the commission's alternatives
    The alternatives outlined by President Clinton's Commission are as 
follows:
    1. Generating ``a few, widely used and well characterized human 
embryonic stem cell lines, genetically altered to prevent graft 
rejection in all possible recipients.'' This would raise its own 
ethical objections because it may involve producing and destroying some 
human embryos at the outset; but it does not require somatic cell 
nuclear transfer, or the creating and destroying of genetically related 
embryos for each individual patient.
    2. Stimulating ``proliferation and differentiation of the quiescent 
stem cells which are known to exist in many adult tissues, including 
even the nervous system.'' Such stem cells could be ``customized'' to 
each individual patient and would not be from embryonic sources.
    3. Identifying ``methods by which somatic cells could be `de-
differentiated' and then `re-differentiated' along a particular path.'' 
This would permit ``the growth of specialized cells compatible with a 
specific individual person for transplantation.'' While at present this 
option is considered speculative, its feasibility is now enhanced by 
the central finding of the research that produced ``Dolly'' the sheep: 
An adult body cell can be ``de-differentiated'' surprisingly easily and 
regressed all the way back to a stage at which it can provide the 
nucleus for a new developing embryo. The question is: Can this 
regression be done to a point short of this, so an adult cell becomes 
the basis for cells that are like embryonic stem cells but never came 
from an embryo?
      other alternatives (not explicitly cited by the commission)
    4. There are other promising sources of pluripotent (not embryonic) 
stem cells for treatment of disease. One example is hematopoietic 
(blood cell producing) stem cells from bone marrow or even from the 
umbilical cord blood in live births. These cells are already widely 
used in cancer treatment and in research on treating leukemia and other 
blood diseases. Their versatility was recently found to be even greater 
than once thought. For example, given the right environment bone marrow 
cells can be used to regenerate muscle tissue, opening up ``a whole 
avenue of potential therapies that didn't exist before'' for muscular 
dystrophies (``Bone Marrow Cells May Provide Muscle Power,'' Science, 6 
March 1998, p. 1456).
    5. An enormously promising new source of stem cells is fetal bone 
marrow, which is ``23 times more effective than adult marrow and eight 
times better than umbilical cord blood.'' Recent studies show that 
``miscarriages can provide enough cells for transplantation if we would 
collect them effectively and store them in banking'' (``Fetal marrow 
transplants promising against disease,'' Detroit News, May 4, 1997). A 
stem cell line from such sources could provide a continuous supply of 
stem cells for research. It seems fetal bone marrow cells do not 
provoke the same immune reactions as adult or even newborn infant 
cells. This is true whether the unborn child is the donor or the 
recipient--that is, fetal cells can be used to treat adults, or adult 
bone marrow cells can be used to treat a child in the womb, without 
harmful immune reactions (see Jack Goldberg, ``Fetal stem cell 
therapy,'' in Jauniaux et al. (eds.) Embryonic Medicine and Therapy 
[Oxford U. Press 1997], pp. 474-80).
    6. Other approaches to tissue regeneration involve the growth 
factors (activators and inhibitors of cell division and growth) 
responsible for the development of various cell types and tissues. 
These factors may be used to manipulate the cells of a tissue along the 
spectrum of differentiation, without the need to create stem cells 
first. Use of these factors has already shown promise in the clinical 
setting, as a vascular growth factor has been successful in saving the 
legs of three patients who had potentially lethal blood clots requiring 
amputation: Application of the growth factor allowed new vessels to 
grow around the clots and restore circulation to the legs (see 
Circulation, 3/31/97, pp. 1114 ff.). Now such factors have been used to 
generate new blood vessels to human hearts in 20 patients (``Drug 
Stimulates Growth of Heart Blood Vessels,'' Washington Post Health, 
Feb. 24, 1998, p. 5).
    7. Cells of different kinds are now being genetically engineered to 
repair damaged organs, especially by injecting them with an 
``oncogene'' (a type of gene that causes cancer cells to reproduce 
rapidly). Heart cells produced with this gene can ``survive and beat 
like normal heart muscle cells'' when transferred to a damaged heart 
(``Study: Cells Repair Heart Damage,'' Associated Press, March 17, 
1998).
    8. Methods are being developed for growing entire replacement 
organs, to treat children before or after birth. Cells of the needed 
variety are extracted from the child and cultured, then grown into 
organs in the laboratory using biodegradable scaffolds. The researchers 
say they hope to receive FDA approval for routine use of the technology 
within five years. They add that ``there are no ethical concerns doing 
this treatment, as there are about some other procedures [such as human 
cloning]'' (``Doctors grow animal organs,'' Washington Times, July 23, 
1997, pp. A1, A18; also see Ben Bova, ``Lost a lung? Grow your own,'' 
in USA Today, Feb. 24, 1998).
    9. Promising avenues have been opened up in research on cancer and 
diseases of aging by studies of telomerase, dubbed by some ``the 
immortality enzyme.'' It protects and rebuilds telomeres, the 
protective caps on the ends of chromosomes which deteriorate as we age. 
It is now believed that telomerase activity is required for the 
uncontrolled growth of most cancerous tumors. Mastering this enzyme may 
enable researchers to (a) inhibit its activity in cancer cells and 
reduce or stop tumor growth, and (b) to use telomerase itself in a 
controlled way to help rejuvenate and regenerate damaged tissues and 
organs. (J. Madeleine Nash, ``The Immortality Enzyme,'' Time, Sept. 1, 
1997).
    In short: The claim that human embryo cloning is needed to advance 
promising medical research in cancer, degenerative diseases, etc. is 
simply false.
    Even if the use of somatic cell nuclear transfer to create and 
cannibalize human embryos were to enable more rapid development of some 
limited branches of research (a proposition for which there is no firm 
evidence), the words of Professor Patricia King, co-chair of the NIH 
Human Embryo Research Panel, would remain valid:
    The fertilization of human oocytes for research purposes is 
unnerving because human life is being created solely for human use * * 
*. In particular, the public should be assured that embryos will not be 
created because such creation is the most convenient means of answering 
important scientific questions that can be answered--perhaps more 
slowly--in other ways.'' [Final Report of the Human Embryo Research 
Panel (NIH, Sept. 27, 1994), p. 97].
STATEMENT OF THOMAS B. OKARMA, Ph.D., M.D., VICE 
            PRESIDENT OF RESEARCH AND DEVELOPMENT, 
            GERON CORP.
    Senator Specter. We turn now to Dr. Thomas Okarma, Vice 
President of Research and Development of Geron Corporation. 
Since 1991 Dr. Okarma has served as a clinical associate 
professor of medicine at Stanford, authored over 100 
publications, and has a dozen U.S. patents, a Ph.D., and M.D. 
from Stanford.
    Thank you for joining us, Dr. Okarma, and the floor is 
yours.
    Dr. Okarma. Thank you for the invitation this morning.
    We have heard ample testimony prior to my time validating 
the significance of the discoveries here, so I will not waste 
our time repeating those, and turn directly to why Geron chose 
to fund this research. Clearly, the therapeutic potential, as 
we have heard, is extraordinary. The potential, however, is 
realizable and portions of it can be reduced to practice based 
upon prior knowledge gained from animal stem cell work and the 
convergence of available complementary technologies developed 
by both the biotech industry and the academic community.
    For example, Geron's demonstrated ability to use the 
telomerase gene to convey unlimited replicative capacity to 
differentiated cells is a key synergistic technology for 
developing the therapeutic applications we have been talking 
about today. Simply stated, as we learn to control the pathways 
that take stem cells down the road to neurons, blood vessels, 
and heart cells, we can immortalize them by telomerase gene 
transfer, so that sufficient quantities of these cells can be 
grown for transplant applications.
    Geron's corporate mission is to develop treatments for 
chronic degenerative disease. These two technologies, 
telomerase gene transfer and human pluripotent stem cells, 
combine to make possible the repair of degenerating organs with 
young, healthy, and fully functional cells.
    Now, why the NIH should participate in the development of 
these applications. As we have heard, the scientific frontier 
opened up by the derivation of these cells is vast. However, 
industry will only explore that part of the frontier that may 
lead to products. Yet, much of this frontier is early basic 
research that would otherwise be underfunded by the private 
sector, thereby delaying and reducing the full impact of the 
discovery.
    Basic mechanisms of early human cellular differentiation, 
intercellular communication, gene expression, and development 
biology are accessible to vigorous study for the first time. We 
must seize this opportunity and allow the most sophisticated 
biotechnology community in the world full access to these cells 
and appropriate levels of support to increase our understanding 
of the fundamental mechanisms that control our own development.
    Last, I would like to summarize the position of Geron's 
ethics advisory board on the ethical justification of this kind 
of work. The company formed an ethics advisory board to advise 
us on the ethical issues associated with this research. The 
board, composed of medical ethicists of diverse religious 
traditions, carefully deliberated the issues and unanimously 
agreed that research on human pluripotent stem cells can be 
conducted ethically if performed within certain guidelines, 
which briefly are: treating the cells with appropriate respect 
due to early developmental tissue; obtaining full and informed 
consent from donors of the tissue; no reproductive cloning of 
human beings; accord for accepted norms of animal research; 
concern for global justice and the use of best efforts to 
develop and utilize the technology for all peoples; and last, 
participation by an independent ethics advisory board, in 
addition to an institutional review board, to assess the 
appropriateness of each research protocol.
    Geron has and will continue to follow these guidelines. I 
have submitted the ethics board's report to this hearing and a 
full publication of these guidelines and their ethical 
foundations will be published by the board in conjunction with 
the Hastings Center.

                           prepared statement

    In conclusion this morning, the therapeutic applications of 
this technology are real and near term. The benefits to society 
are clear, and their development appropriately falls under the 
purview of the National Institutes of Health. The ethical 
implications of the research, while requiring continual 
oversight as the technology matures, are nevertheless 
compelling today and argue strongly for the development and 
application of this technology for the improvement of health 
care.
    Senator Specter. Thank you very much, Dr. Okarma.
    [The statement follows:]
                  Prepared Statement of Thomas Okarma
                           executive summary
    First, I would like to thank the committee for inviting my 
testimony on behalf of Geron Corporation on the implications of human 
stem cell research. My comments will briefly cover (l) the significance 
of the discovery, (2) why Geron chose to support this research, (3) why 
the NIH should participate in the development of biomedical 
applications of this research and (4) the view of Geron's Ethics 
Advisory Board on the ethical justification for research on the human 
pluripotent stem cell.
    I respectfully request that my comments and submitted background 
materials be incorporated into the record of this hearing.
    1. The significance of the discovery.--The human pluripotent stem 
cell has the potential to dramatically impact clinical medicine by 
introducing fundamentally new therapeutic technologies. No other human 
cell has the potential to (1) enable the development of cell and tissue 
transplantation therapies and gene therapy, (2) retool pharmaceutical 
research and development, and (3) accelerate research in human 
developmental biology, cellular differentiation mechanisms and cancer 
biology.
    These cells are immortal in their undifferentiated state--they will 
grow indefinitely in culture, thereby providing a continuous source of 
homogeneous starting material for the production of uniform 
transplantable cells.
    These cells are pluripotent, capable of forming all cells of the 
human body, making them a potential source of replacement cells for any 
failing organ. This would reduce the demand for organ donors, and more 
importantly, enable therapies to treat conditions that otherwise must 
be addressed by whole organ transplants such as:
  --Heart muscle cells to restore the failing hearts of the five 
        million Americans with congestive heart failure.
  --Blood forming cells to provide hematologic support for the over one 
        million new cases of invasive cancer in the US each year.
  --Cells to line the inside of blood vessels to treat atherosclerosis 
        which contributes to 650,000 deaths in the US each year.
  --Insulin producing islet cells which could cure the 1.4 million US 
        patients with Insulin Dependant Diabetes Mellitus.
  --Nerve and brain cells for the one million Parkinson's disease 
        patients, the 500,000 stroke victims or the four million 
        Americans with Alzheimer's disease.
    2. Why Geron chose to fund this research.--Clearly, the therapeutic 
potential is extraordinary. This potential is realizable and portions 
of it can be reduced to practice based upon prior knowledge gained from 
animal stem cell work, and the convergence of available complimentary 
technologies developed by both the biotechnology industry and the 
academic biomedical community. For example, Geron Corporation's 
demonstrated ability to use the telomerase gene to convey unlimited 
replicative capacity to differentiated cells is a key synergistic 
technology for developing therapeutic applications of human pluripotent 
stem cells. As we learn to control the pathways that take stem cells 
down the road to neurons, blood vessels, and heart cells, we can 
immortalize them by telomerase gene transfer so that sufficient 
quantities of these cells can be grown for transplant applications.
    Geron's mission is to develop treatments for chronic, degenerative 
disease. These two technologies, telomerase gene transfer and human 
pluripotent stem cells, combine to make possible the repair of 
degenerating organs with young, healthy and fully functional cells.
    3. Why the NIH should participate in the development of biomedical 
applications of this research.--The scientific frontier opened up by 
the derivation of human pluripotent stem cells is vast. Industry will 
only explore that part of the frontier that may lead to products. Yet 
much of this frontier is early, basic research that will be otherwise 
underfunded by the private sector, thereby delaying and reducing the 
full impact of this discovery. Basic mechanisms of early human cellular 
differentiation, intercellular communication, gene expression and 
developmental biology are accessible to vigorous study for the first 
time. We must seize this opportunity and allow the most sophisticated 
biomedical research community in the world full access to these cells 
and appropriate levels of support to increase our understanding of 
these fundamental mechanisms that control our own biological 
development.
    4. The position of Geron's Ethics Advisory Board on the ethical 
justification of research on human pluripotent stem cells.--Geron 
formed an Ethics Advisory Board to advise the company on the ethical 
issues associated with this research. The board, composed of medical 
ethicists of diverse religious traditions, carefully deliberated the 
issues and unanimously agreed that research on human pluripotent stem 
cells can be conducted ethically if performed within certain 
guidelines:
    (1) Treating the cells with respect appropriate to early 
developmental tissues. As stated by the Human Embryo Research Panel in 
their 1994 report, while deserving moral consideration due any human 
tissue, the early blastocyst (from which the stem cells are derived) 
does not warrant the same moral status as infants or children because 
of the absence of individuation and the lack of even the possibility of 
sentience and other qualities relevant to the moral status of persons. 
Therefore the use of such cells for the purpose of saving or healing 
human life constitutes appropriate respect for these cells.
    (2) Full and informed consent for tissue donation.
    (3) No reproductive cloning of human beings or creation of chimeras 
(live animal combinations of two different species).
    (4) Accord for accepted norms for animal research.
    (5) Concern for global justice and the use of best efforts to 
develop and utilize the technology for all peoples.
    (6) Participation by an independent ethics advisory board in 
addition to an Institutional Review Board to access the appropriateness 
of each research protocol.
    Geron has and will continue to follow these guidelines. I have 
submitted the EAB's report to this hearing. A full publication on these 
guidelines and their ethical foundations will be published by the Board 
in conjunction with the Hastings Center.
    In conclusion, the therapeutic applications of this technology are 
real and near term. The benefits to society are clear and their 
development appropriately falls under the purview of the NIH. The 
ethical implications of this research, while requiring continual 
oversight as the technology matures, are nevertheless compelling and 
argue strongly for the development and application of this technology 
for the improvement of health care.
           the first derivation of human embryonic stem cells
A Scientific Breakthrough for Transplantation Medicine, Pharmaceutical 
        Research and Development, and Human Developmental Biology
            The Breakthrough
    Dr. James Thomson and colleagues at the University of Wisconsin, 
Madison, have for the first time successfully derived human embryonic 
stem cells (hES cells) and maintained them in tissue culture. Human 
embryonic stem cells are different from every other human stem cell 
previously isolated in that they have (i) an unlimited ability to 
divide and (ii) the capability to turn into any and all cell types and 
tissues in the body. These cells, licensed worldwide to Geron 
Corporation, hold great promise as a potentially universal source of 
replacement cells for transplantation and for use in screens for 
pharmaceutical research and development. Further, this promise is 
enhanced by Geron's cell immortalization technology which can 
potentially increase the lifespan of the differentiated cells produced 
from hES cells. The combined technology positions Geron to potentially 
supply an unlimited number of young cells and tissues for every organ 
in the body. In addition, hES cells will improve our understanding of 
reproductive and developmental biology. This could lead to better 
treatments for infertility and the discovery of new gene products to 
treat a wide variety of diseases.
            Characteristics of Human Embrvonic Stem Cells
    Derived from in vitro fertilized (IVF) blastocysts by a patentable 
laboratory process (US claim allowed) and donated under informed 
consent, hES cells have all the following characteristics which make 
them useful for multiple new therapeutic, pharmaceutical, and 
scientific applications.
    1. Pluripotency.--hES cells can form virtually any cell in the 
body. Specifically they have the potential to form derivatives of all 
three cellular layers, including the gut epithelium (endoderrn); 
cartilage, bone, and smooth and striated muscle (mesoderm); and neural 
epithelium, embryonic ganglia and stratified squamous epithelium 
(ectoderm). Other later stage human stem cells have only a limited 
capability to form certain cell types such as blood cells (CD34+ stem 
cells) or connective tissue (mesenchymal stem cells).
    2. Self-renewing capacity.--Under appropriate in vitro conditions, 
the hES cells repopulate themselves while remaining in the 
undifferentiated state. Therefore, they may be a continuous source of 
normal pluripotent human stem cells. We expect they can be scaled-up to 
commercial manufacturing levels for transplantation therapies. It has 
not been possible to maintain long term self-renewing capacity of other 
human stem cells in culture. The ability of hES cells to propagate 
indefinitely in the undifferentiated state without losing pluripotency 
is a characteristic that distinguishes them from all other 
``multipotent stem cells'' discovered to date in humans. Among other 
benefits, the availability of scaled-up hES cell-derived cells and 
tissues for transplantation therapies could greatly reduce future 
reliance on primary human fetal and animal derived tissue.
    3. Telomerase expression.--Telomerase is an RNA-dependent DNA 
polymerase demonstrated by Geron Corporation and its collaborators to 
be the enzyme which, when reactivated in normal cells, allows their 
continual proliferation. hES cells normally express the enzyme 
telomerase. The continual steady state activity of telomerase in hES 
cells conveys replicative immortality. Other stem cells express 
telomerase at low levels or only periodically and therefore age and 
stop dividing with time.
    4. Normal chromosome structure (karyotvpe).--hES cells maintain a 
structurally normal set of chromosomes (including the sex chromosomes, 
XX or XY) even after prolonged growth in vitro. They do not, for 
example, have any additions, deletions or rearrangements in their 
chromosomal structure as is characteristic of cell lines immortalized 
by viruses.
    Because of these characteristics, hES cells are unique. No other 
cell has the potential of hES cells to (i) enable development of 
transplantation therapies, (ii) re-tool pharmaceutical research and 
development practices, and (iii) accelerate research in human 
developmental biology. Moreover, hES cells should provide an immediate, 
alternative source and industrial supply of starting material, 
relieving the need to continually resource primary human fetal-derived 
tissues. Much of the research necessary for product development work 
can be performed on the hES cells now made available by Dr. Thomson's 
breakthrough discovery. This research will be challenging and take 
time, yet holds vast biomedical and therapeutic potential. Geron 
Corporation has provided funding and support for Dr. Thompson's work 
and holds worldwide rights to his discovery.
            Benefits to Science and Medicine
    The derivation of hES cells is a fundamental discovery that holds 
promise for three major areas of biomedicine: (1) Transplantation 
medicine, (2) Pharmaceutical research and development and (3) Human 
developmental biology.
    1. Transplantation Medicine.--The potential therapeutic impact of 
hES cells in transplantation medicine is enormous because of their 
expected capability to produce virtually unlimited quantities of any 
cell in the body. In addition, they have the potential to be 
genetically engineered to prevent their immune rejection by the 
transplant recipient. Examples of medically relevant cells that could 
be developed and tested for transplantation therapies in humans include 
the following:
    (i) Cardiomyocytes.--Heart muscle cells do not proliferate during 
adult life. When heart muscle is damaged by injury or ischemia, 
functional heart muscle is replaced with non-functional scar tissue. 
Congestive heart failure, a common consequence of heart muscle or valve 
damage, affects nearly 5 million people in the United States, with 
400,000 new cases diagnosed each year. In addition, about 1.5 million 
people each year suffer myocardial infarction, the primary cause of 
heart muscle damage, and about one third of them die.
    Mouse cardiomyocytes derived from mouse embryonic stem cells have 
been prepared and injected into the hearts of recipient adult mice. The 
injected cardiomyoctes repopulated the myocardial tissue and stably 
integrated with host myocardial tissue (Klug, et al., 1996, J Clin 
Invest 98:216-224). These results suggest that the development of hES 
cell-derived cardiomyocytes for cellular transplantation therapy of 
congestive heart failure and myocardial infarction in humans is 
technically feasible.
    (ii) Hematopoietic stem cells.--Bone marrow transplantation is a 
life saving procedure used in pediatric and adult cancers. In 1995, 
there were approximately 4,500 allogeneic (donor) and 8,000 autologous 
(self) blood and bone marrow transplants performed in North America. 
The number of procedures performed dramatically under-serves the 
medical need. The main factor which limits the number of procedures is 
tissue or donor availability.
    Blood-forming stem cells could be developed from hES cells as has 
been done using mouse embryonic stem cells (Kennedy, et al., 1997, 
Nature 386:488-492). This would increase the availability of these 
cells and reduce reliance on donors. Further, hES cell-derived 
hematopoietic stem cells potentially could be genetically engineered to 
resist infection by such agents as the HIV virus and used in a 
transplant setting for the treatment of AIDS, or possibly used for the 
treatment of patients with sickle cell anemia.
    (iii) Endothelial cells.--(blood vessel forming cells). Endothelial 
cells have been observed in hES-derived teratomas in mice and mouse 
endothelial cells have been derived from mouse ES cells (Vittet, et 
al., 1996 Blood 88:3424-3431). These blood vessel forming cells could 
be generated from hES cells and used to re-line blood vessels for the 
purpose of treating atherosclerosis, a condition which contributes to 
over 650,000 deaths annually in the US. hES-derived endothelial cells 
could also be used for generating new blood vessels in ischemic regions 
of the heart, brain, or lower extremities to treat angina, stroke and 
arterial insufficiency.
    (iv) Islet cells.--The 1.4 million U.S. patients with Insulin 
Dependant Diabetes Mellitus potentially could be treated with islet 
cells derived from hES cells and isolated for this use. Such human 
cells are unavailable today and could provide a lifelong cure for this 
disease.
    (v) Neurons.--It has been demonstrated that mouse neurons can be 
derived from mouse embryonic stem cells (Bain, et al., 1995, Dev Biol 
168:342-357). Neurons derived from hES cells potentially could be 
prepared for the treatment of (i) the over 1 million individuals in the 
United States who suffer from Parkinson's disease, (ii) the 500,000 
U.S. citizens who suffer a stroke each year, and (iii) even Alzheimer's 
disease, which now affects over four million Americans.
    (vi) Fibroblast and keratinocyte skin cells.--of mice have been 
observed in cultures of differentiated mouse ES cells (Bagutti, et al., 
1996, Dev Biol 179:184-196). We expect that comparable human skin cells 
could be produced from hES cells and used for wound healing and the 
treatment of burns.
    (vii) Chondrocytes.--cartilage forming cells, also observed in hES-
derived teratomas in mice, could potentially be generated from hES 
cells for cartilage replacement in osteoarthritis which affects over 16 
million Americans, or rheumatoid arthritis which affects over two 
million persons in the United States.
    2. Pharmaceutical research and development.-- The potential to 
produce and supply unlimited quantities of normal human cells of 
virtually any tissue type could have a major impact on pharmaceutical 
research and development. Until now, the only cell lines available for 
this work were either animal in origin or abnormal transformed human 
cells. Permanent, stable sources for normal human differentiated cells 
may be developed for drug screening and testing, drug toxicology 
studies, as well as new drug target identification. Further, because 
hES cells express telomerase and can therefore undergo multiple rounds 
of a sophisticated type of genetic engineering called gene targeting, 
cellular models of human disease could be developed for use in drug 
development. Finally, cell lines derived from hES cells may be useful 
for developing screens for teratogens (drugs causing birth defects), 
extending the capability of current assays based on bacterial and 
murine systems.
    3. Human reproductive and developmental biology.--Unraveling the 
biology of hES cells as they differentiate into functional cell types 
in vitro offers a unique platform to understand and harness nature's 
mechanisms of embryonic development, tissue differentiation and repair. 
Such understanding has potential for contributing to (i) the treatment 
of fertility disorders which affect one out of every six couples in the 
U.S. trying to become pregnant, (ii) the prevention of premature 
pregnancy loss, estimated to be 15 percent of recognized pregnancies in 
the US, and (iii) the diagnosis and prevention of birth defects which 
afflict 3 percent of live births in the US.
    Until now, the early developmental events which naturally occur 
during human embryogenesis have been inaccessible to direct study. The 
availability of hES cells may facilitate a molecular understanding of 
how specific human tissues and organs develop without conducting 
research on human embryos or fetuses. Further, it is possible that 
novel genes which fundamentally control tissue differentiation could be 
identified by the application of genomic technologies to cultured hES 
cells as they differentiate into a variety of functional cell types. 
These new gene products may have potential to be developed into 
therapeutic proteins with possible applications including wound 
healing, stroke, myocardial infarction, spinal cord injury, and tissue 
regeneration.
    These potential clinical applications would utilize suspensions of 
hES cell-derived differentiated cells administered by injection. With 
further technical development, complex multi-cellular solid tissues and 
organs potentially could be developed for application in organ support 
therapies for lung, kidney, liver, cardiac and brain diseases. While 
the biomedical and therapeutic promise of hES cells is vast, it should 
be emphasized again that the additional research and development 
required to realize this potential is significant.
            This Breakthrough is Enhanced by Geron's Technology
    Geron's focus is on identifying and modifying for therapeutic 
purposes the molecular mechanisms that control cellular aging and 
replication. The company and its collaborators have cloned the enzyme 
telomerase which extends the replicative capacity of cells. The 
application of telomerase gene transfer technology to hES cells is part 
of Geron's ongoing work in cell and gene therapy and flows from its 
published results on extending cellular replicative potential as 
reported in Science earlier this year (Bodnar, et al., 1998, Science 
349-352). Telomerase activity is quickly down-regulated after hES cells 
differentiate. The ability to reactivate telomerase in differentiated 
cells derived from hES cells could prolong their replicative lifespan 
indefinitely and thereby make them the preferred cells for applications 
in transplantation medicine because they should be long-lived and form 
a durable graft.
            The History of hES Cell Derivation
    Work to derive and maintain undifferentiated pluripotent cell lines 
dates back to the 1960s with the demonstration that certain cancer-
derived mouse cells were capable of forming multiple tissue types. 
These cancerous cells proved to be of limited research utility, and 
efforts continued to derive non-cancerous, self-renewing, pluripotent 
stem cells from mouse embryos. Eventually, the successful derivation of 
murine embryonic stem cells from the inner cell mass of mouse 
blastocysts in 1981 allowed culture conditions to be defined that 
supported their unlimited propagation. These cells were soon shown to 
be totipotent and capable of contributing to the germ line in mice 
(passed on from generation to generation). The use of murine embryonic 
stem cells in gene targeting experiments has resulted in development of 
numerous mouse models of human disease (knock-out mice) and has 
provided valuable insights into developmental biology, much of which 
has been applied to human medicine. However, these experiments also 
demonstrated that there are major differences in developmental biology 
between mice and humans. These fundamental differences formed a 
rationale to pursue the derivation of embryonic stem cells from higher 
mammals.
    Methods developed for deriving mouse embryonic stem cells were 
applied toward deriving embryonic stem cell lines from other animals 
such as sheep (1987), hamster (1988), pig (1990), and rabbit (1993). 
The first non-human primate embryonic stem cell was described by Dr. 
James Thomson at the University of Wisconsin, Madison in 1995. The 
derivation process for primate embryonic stem cells differed from 
methods developed for the mouse and other non-primate species. 
Furthermore, there are differences between primate ES cells and other 
ES cells. For example, currently, primate embyonic stem cells have a 
absolute requirement for feeder layers of irradiated fibroblasts in 
order to propagate in the undifferentiated state in vitro. They also 
differ from mouse ES cells in colony appearance and biochemical surface 
markers.
    Like other mammalian embryonic stem cells, however, primate 
embryonic stem cells differentiate and form tissues of all three 
cellular layers when injected into immunodeficient mice, proving their 
pluripotency. Published reports show that these primate embryonic stem 
cells have been maintained in culture for more than a year, during 
which time they have retained their pluripotency, self-renewing 
capacity, and their normal karyotype (Thomson, et al., (1995), PNAS 
92:7844-7848).
    Dr. Thomson subsequently applied his primate embryonic stem cell 
derivation technology to voluntarily donated in vitro fertilized human 
blastocysts. He now reports the first successful derivation and 
propagation of human embryonic stem cells which, like the primate 
embryonic stem cells derived earlier, are pluripotent,\1\ self 
renewing, and telomerase positive with a normal karyotype (Thomson, et 
al., (1998) Science, in press).
---------------------------------------------------------------------------
    \1\ hES cells are referred to as pluripotent. All non-human ES 
cells are referred to as totipotent (capable of developing into the 
whole organism). The only way to prove totipotency is to derive an 
organism from the cell. This has been done with animal ES cells but 
will not be done with hES cells for ethical reasons.
---------------------------------------------------------------------------
            The Derivation of Human Embryonic Stem Cells
    In vitro fertilized preimplantation stage blastocysts, produced 
initially but not used for clinical purposes, were donated voluntarily 
with conformed consent, by clients undergoing in vitro fertilization 
procedures. The derivation protocols were approved by the University of 
Wisconsin Institutional Review Board. After culturing to the blastocyst 
stage, the inner cell masses were recovered and cultured on irradiated 
mouse embryonic fibroblast feeder layers. After about two weeks in 
culture, the hES cells were dissociated and replated on fresh feeder 
layers. The hES cells were thereafter maintained for months in the 
undifferentiated state by serially sub-culturing onto fresh, irradiated 
mouse embryonic fibroblast feeder layers (Fig 1).
            The Demonstration of Pluripotency
    The capability of hES cells to differentiate into virtually any 
cell in the body was demonstrated by experiments in which the hES cells 
were injected into severe combined immunodeficient (scid) mice. Each of 
the injected cell lines produced non-malignant tissue masses 
(teratomas) that contained a wide range of human differentiated cells 
and tissues, including gut epithelium (endoderm); cartilage, bone, 
smooth and striated muscle (mesoderm); and neural epithelium, embryonic 
ganglia and stratified squamous epithelium (ectoderm). These three 
cellular layers (endoderm, mesoderm and ectoderm) have the potential to 
form all the cells in the body (Fig 2).
            The Significance of Telomerase Expression in hES Cells
    In general, cells that express telomerase have the ability to 
divide indefinitely. Cells not expressing telomerase (most cells of the 
body) have a limited replicative capacity. hES cells express telomerase 
and therefore have infinite replicative capacity.
    Telomerase is an enzyme, cloned by Geron and collaborators, that 
maintains the length of the telomeric regions (ends) of chromosomes and 
thereby prevents cell senescence. In fact, telomerase expression is 
highly correlated with replicative immortality in certain human cells. 
Similarly, re-introduction of telomerase by gene transfer into normal 
telomerase-negative cells confers replicative immortality (Bodnar, et 
al., 1998, Science 349-352). Telomerase activity is continuously 
present in adult male reproductive tissue and is present in human fetal 
heart, liver, and kidney cells but only for the first 11-15 weeks of 
embryonic development.
    The benefits of telomerase expression in hES cells are twofold. 
First, the cells are immortal, enabling the production of an unlimited 
supply of undifferentiated pluripotent cells. Second, the cells are 
amenable to a sophisticated type of genetic engineering called gene 
targeting which allows the insertion of new genes to specific sites on 
the chromosome to enhance their expression and control.
            Geron's Intellectual Property Position in hES Cells
    Geron's intellectual property estate in the embryonic stem cell 
field consists of:
    1. A worldwide license to the stem cell patent estate of Dr. James 
Thomson and the Wisconsin Alumni Research Foundation. Licensed patent 
applications include primate and human embryonic stem cells and related 
diagnostic and therapeutic products. A broad claim has already been 
allowed in the US from this estate covering primate embryonic stem 
cells with the characteristics described in the Thomson Science paper 
just published.
    2. A worldwide license to the stem cell patent estate of Dr. John 
Gearhart and the Johns Hopkins University. This license includes all 
applications of human embryonic stem cells including diagnostic and 
therapeutic products.
    3. A worldwide license to patent applications of Dr. Roger Pedersen 
and the Regents of the University of California covering diagnostic and 
therapeutic products based on hES cells.
    4. A license of the Genpharm patents on genetic modification of 
human and primate embryonic stem cells by homologous recombination 
(gene targeting). This estate consists of four issued US patents and 
eight pending US patent applications.
    5. Geron-owned patent applications including screens for hES cell 
growth factors, media formulation and preferred growth conditions, and 
also relating to telomerase gene transfer and recombinant telomerase 
expression in embryonic stem cells and their derivatives.
            The Ethical Considerations in hES Cell Product Development
    These hES cells are derived from in vitro fertilized blastocysts. 
IVF clinic patients voluntarily donated the blastocysts with informed 
consent. The University of Wisconsin-Madison Institutional Review Board 
approved all of the research protocols. Geron's intended hES cell 
research as well as that of its collaborators is conducted within the 
suggested guidelines of the 1994 report by the NIH Human Embryo 
Research Panel.
    Human embryonic stem cells are obtained from in vitro fertilized 
human blastocysts and capable of differentiating into virtually any 
cell in the body. However, hES cells are derived from the blastocyst 
inner cell mass by a laboratory process and are not the cellular 
equivalent of an embryo.
    The small cluster of cells (inner cell mass) within the in vitro 
fertilized blastocyst from which the hES cells are derived have not yet 
differentiated and are unspecialized. The inner cell mass does not form 
discrete parts of an individual embryo as one or more of these inner 
mass cells can be removed from the blastocyst (for preimplantation 
diagnosis) without affecting subsequent fetal development after 
transfer to the uterus. If hES cells were to be transferred to a 
uterus, the hES cells would not form an embryo because other cells 
necessary for implantation and embryogenesis have been lost in the 
derivation process.
    Geron has adopted the conclusion of the NIH Human Embryo Research 
Panel in its 1994 report. The cells will not be used for (i) cloning 
humans, (ii) transfering to a uterus, or (iii) generating human-human 
or human-animal chimeras (live animal hybrids produced by mixing 
embryonic stem cells of different individuals or species).
    Geron has formed an independent Ethics Advisory Board composed of 
prominent bioethicists to advise the company on the ethical 
implications of hES cell product development strategies. The Board has 
unanimously agreed that research on hES cells can be conducted 
ethically if performed within the guidelines adopted by Geron 
Corporation and its collaborators. To complement its internal research 
and development, Geron Corporation maintains sponsored research 
collaborations with Dr. James Thomson, Dr. John Gearhart and Dr. Roger 
Pedersen, nationally prominent investigators in human stem cell 
research whose protocols have all been reviewed and approved by their 
respective Institutional Review Boards.
            The Next Steps in hES Cell Research and Development
    Now that the major bottleneck in developing hES cell-derived cells 
and tissue for transplantation has been eliminated with the derivation 
of hES cells, Geron plans to develop other supporting technologies 
including:
    (i) Human embryonic stem cell production, scale up and genetic 
engineering.--A standardized process will need to be developed for 
large-scale production of hES cell-derived differentiated cells for 
transplantation. Quality control criteria will need to be developed for 
the feeder lines, culture media, growth factors, sterility assays and 
phenotypic markers used for the clinical production of hES cells. 
Protocols will need to be developed and optimized for genetically 
engineered hES cells. Techniques of gene targeting \2\ (homologous 
recombination) will need to be optimized.
---------------------------------------------------------------------------
    \2\ Gene targeting is a sophisticated technique of genetic 
engineering which allows the gene of interest to be ``targeted to'' a 
specific and desired location in the chromosome, thereby allowing the 
gene of interest to be controlled by the normal regulators of that 
gene's expression. Because gene targeting requires several rounds of 
selection, each requiring multiple cycles of cell division, only 
immortalized cells have sufficient replicative capacity to be suitable 
for this form of genetic engineering.
---------------------------------------------------------------------------
    (ii) Differentiation control.--Technologies using tissue-specific 
promoters and drug selection strategies will need to be developed to 
direct the differentiation of these cells towards the desired final 
cell and tissue product. Other methods of cell purification such as 
cell sorting will also need to be explored. Factors useful to drive 
cells toward specific differentiation states will need to be identified 
and used in conjunction with drug selection-enrichment technologies. 
Techniques will need to be developed to prevent the rejection of hES 
cell derived tissues by transplant recipients.
    (iii) Primate model development.--Human therapeutic products 
derived from hES cells will require in vitro and animal testing. With 
Geron's license to the non-human primate embryonic stem cells of 
monkeys (also identified by Dr. Thomson at the University of Wisconsin-
Madison), Geron has the capability to develop and test its proposed 
therapeutic products in a highly useful primate model.
    This continuing research and development activity will constitute 
Geron Corporation's hES cell technology development program. Geron has 
work plans in place with Drs. Thomson, Gearhart and Pedersen, and will 
seek to collaborate with other academic centers and biotechnology and 
pharmaceutical companies in developing these therapeutic opportunities.
    The availability of pluripotent, self-renewing hES cells that can 
be differentiated into bulk-manufactured, functional, youthful cells 
and tissues will potentially usher in a new era of therapeutic 
opportunities in transplantation medicine, pharmaceutical research and 
development, and developmental biology that could positively impact 
many millions of patients worldwide.
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[GRAPHIC] [TIFF OMITTED] T07DE02.002

                                glossary
First Derivation of Human Embryonic Stem Cells
    Allogeneic: When describing transplantation biology, the donating 
individual is of the same species, but not one's self.
    Angina: A condition with severe and constricting pain, usually 
referring to the heart.
    Autologous: When describing transplantation biology, the donating 
individual is one's self.
    Blastocyst: In mammalian embryology, the preimplantation embryo 
consisting of a sphere of cells with an outer cell layer, a fluid-
filled cavity, and a cluster of cells on the interior that is the inner 
cell mass.
    Cardiomyocytes: Mature, differentiated heart muscle cells.
    Chondrocytes: Mature, differentiated cartilage cells chromosomes: 
Composed chiefly of DNA, they are the carrier of genes, the hereditary 
information.
    Cloning: A term that is applied to genes, cells or entire organisms 
that are derived from, and are genetically identical to, a single 
common ancestor gene, cell, or organism, respectively.
    Differentiate: To undergo a cellular progression to a more 
specialized type.
    Embryo (human): An organism at its earliest stage of development 
which has the potential, if transferred to a uterus, to develop in the 
normal course of events into a living human being.
    Embryogenesis: The process of embryo formation.
    Feeder layers of irradiated mouse fibroblasts: mouse cells which 
have been treated to prevent their division, but which produce 
important growth factors allowing ES cells to repopulate.
    Fibroblast cells: Cells that give rise to connective tissue.
    Keratinocytes: Cells that synthesize keratin as in the skin, hair, 
and nails.
    Gene targeting: The insertion of DNA into specific sites or genes 
within the genome of selected cells to alter gene expression for 
therapeutic applications.
    Genome: The genetic material (complete set of chromosomes) of an 
organism.
    Genomic technology: Sequencing genes and their expression products.
    Hematopoietic: Pertaining to the formation of blood cells.
    hES cells: Human embryonic stem cells, they are immortal (self-
renewing), telomerase positive, and pluripotent.
    Homologous recombination: A process whereby a specific gene 
sequence within the genome is replaced with a related gene sequence 
using the cellular recombination enzymes.
    Inner cell mass: The cluster of cells within the blastocyst from 
which hES cells are derived.
    Implantation: Attachment of a blastocyst to the endometrium.
    In vitro: Performed in an artificial environment such as a test 
tube.
    In vivo: Performed in a living organism.
    In vitro fertilization (IVF): An assisted reproduction technique in 
which fertilization is accomplished outside of the body.
    Ischemia: Deficiency of oxygen in a tissue due to obstruction of a 
blood vessel.
    Islet cells: Cells of the pancreas that produce and secrete 
insulin; degeneration of islet cells is the cause of Insulin Dependent 
Diabetes Mellitus.
    Karyotype: The chromosomal characteristics of a cell.
    Knock-out mice: Mice that have had one or both copies of a specific 
gene deleted or inactivated Page Three/First Derivation of Human 
Embryonic Stem Cells.
    Murine: Of or relating to the rodent family.
    Myocardial infarction: Heart attack.
    Pluripotent: The ability to develop into multiple cell types 
including all three embryonic lineages forming the body organs, nervous 
system, skin, muscle, and skeleton.
    Severe combined imunodeficient (scid) mice: Mice with the majority 
of their immune defenses not functioning.
    Telomerase: An enzyme composed of a protein and an RNA template 
which synthesizes telomeric DNA at the ends of chromosomes and confers 
replicative immortality to cells.
    Telomeres: The ends of chromosomes.
    Teratoma: A non-malignant tumor consisting of different types of 
tissue caused by the growth of embryonic stem cells at an abnormal site 
in the body.
    Totipotent: The ability of a cell to give rise to all cells and 
tissues in the body including the reproductive organs.
    Undifferentiated: Having no limited or specialized function or 
structure, as in stem cells.
    Zygote: Cell formed by union of two gametes--male and female germ 
cells.
                                 ______
                                 
                         Questions and Answers
Science/Technical
    Question. What is the relationship between human ES cells and other 
human stem cells?
    Answer. First, under appropriate in vitro conditions, hES cells 
repopulate themselves while remaining in the undifferentiated state. 
They are, therefore, a potentially continuous source of pluripotent 
human stem cells which could be developed to generate specific cells or 
tissues and scaled-up to commercial manufacturing levels for 
transplantation therapies. It has not been possible to maintain in 
vitro long term self-renewing capacity in the undifferentiated state 
with any other human stem cell. The ability of hES cells to propagate 
indefinitely in the undifferentiated state without losing pluripotency 
is one of the characteristics that distinguishes them from all other 
stem cells discovered to date in humans.
    Second, other human stem cells have only a limited capacity to form 
differentiated cell or tissue types such as blood cells (CD34+ stem 
cells) or connective tissues (mesenchymal stem cells). hES cells, in 
contrast, have the unique capability to form any and all cell and 
tissue types in the body.
    Question. Could these cells be used to grow entire organs?
    Answer. Human Embryonic Stem cells form differentiated tissues with 
organ-like features when injected into immuno-compromised mice. Under 
appropriate laboratory conditions and with the development of 
supportive technologies, it may be possible to grow multicellular 
tissues and perhaps whole organs in a laboratory environment for 
subsequent therapeutic applications in humans.
    Question Will additional hES cells be derived?
    Answer. Although much of the basic research and developmental work 
required to translate this discovery into products of medical value can 
be performed on the hES lines already isolated by Dr. Thomson, other 
hES lines will be isolated to support product development. Because the 
cells are believed to be immortal and pluripotent, and are amenable to 
sophisticated forms of genetic engineering, we envision the possibility 
of producing multiple types of transplantable tissues from single hES 
lines, reducing the necessity to routinely generate new ES cell lines 
for each application.
    Question. How does this technology relate to cloning human beings?
    Answer. As has been documented with animals, the basic technology 
required to clone mammals is already available, although not at this 
point reduced to reliable practice. Dolly was one success in 278 
attempts. To our knowledge, Dolly and all other animals cloned to date, 
were cloned using nuclear transfer procedures which utilize adult cell 
nuclei and enucleated egg cell cytoplasm, not embryonic stem cells. 
Using nuclear transfer procedures, it might be possible in the future 
to clone human beings, without use of hES cell technology.
    However, Geron fully supports the current ban in the State of 
California on cloning human beings for reasons outlined in the 1997 
report of the National Bioethics Advisory Commission on human cloning.
Medical Potential
    Question. What are the hurdles to developing therapeutic 
applications of this technology--for example, growing heart muscle 
cells for heart disease patients?
    Answer. Many lessons have been learned from animal experiments with 
heart muscle, nerve and certain blood cells. For example, heart muscle 
cells have been derived from mouse embryonic stem cells and have been 
injected into hearts of adult mice where they were shown to 
functionally integrate into the heart muscle. In order to accomplish 
this, the mouse embryonic stem cells were genetically modified using 
procedures that allowed the selection of only cardiomyocytes from the 
differentiating cultures. These genetically-based differentiation 
technologies will need to be tested in primate and hES cells in an 
attempt to produce cardiomyocytes of sufficient purity.
    Question. How long will it take before you begin any human clinical 
trials using this technology?
    Answer. Many technologies will need to be developed to realize the 
full potential of the clinical applications of hES cells. Furthermore, 
these applications, once developed, will need to be tested in primate 
models. It is therefore difficult to predict how soon human clinical 
trials using this technology could begin.
    Question. Would it be easier--and just as effective--to work with 
stem cells further downstream, that have already differentiated into 
specific cell types?
    Answer. There are several approaches now in human clinical trials 
that utilize mature, multipotent stem cells (blood-forming cells, 
neuron-forming cells and cartilage-forming cells). These human trials 
will provide valuable insights toward the use of stem cells in 
transplantation procedures. However, each of these approaches requires 
that an individual donor (or the patient) be used as the source of the 
cells which are then subsequently processed in a laboratory and 
transplanted. These procedures, necessary to address tissue sourcing 
constraints and immune system rejection, are costly, time consuming, 
and inefficient. These downstream stem cells have already 
differentiated and are therefore more difficult to modify to make them 
tissue compatible.
    Telomerase positive hES cells, on the other hand, are believed to 
be self-renewing and therefore scalable. One culture line can produce 
many different tissues thereby improving production efficiency. We also 
believe that hES cells, because they are more primitive and 
developmentally upstream, could be more likely to develop into fully 
functional integrated tissues once transplanted. Further, these hES 
cells potentially can undergo multiple rounds of sophisticated genetic 
engineering to become tissue compatible, thereby eliminating the need 
to identify compatible donors as a source of the cells.
Business Issues
    Question. How is Geron involved in this breakthrough?
    Answer. We have funded Dr. Thomson's research for three years and 
collaborated with his lab on the characterization of the hES cells he 
derived. Geron also has a worldwide license to this discovery.
    Question. What evidence is there to support that there will be any 
viable commercial uses based on this discovery?
    Answer. Several of the proposed hES cell-based therapeutic 
applications have already been demonstrated in mice with murine ES 
cells. Geron believes it is likely that these technologies will be 
transferable with appropriate modifications. We believe that results 
achieved in animals potentially can be extended and developed into 
viable therapeutic strategies for humans.
    Furthermore, there are commercial applications of hES technology 
that could be reduced to practice before the cells become available for 
tissue transplantation. We expect to collaborate with one or more 
genomics companies to identify novel genes that could be used to 
generate therapeutic proteins to help regenerate tissue in such 
conditions as spinal cord injury, stroke, or heart attacks.
    Also, cells derived from hES cells may also be commercialized as a 
technology for use in drug screening, drug target identification or 
even identifying teratogens (drugs that cause fetal abnormalities) and 
therefore make the pharmaceutical research and development process more 
efficient.
    Question. What will Geron's sustainable advantage be in competing 
with other stem cell companies?
    Answer. Human embryonic stem cell technology fits in extremely well 
with Geron's telomere and telomerase technology platform. Geron and its 
collaborators have cloned the telomerase enzyme and demonstrated its 
utility in immortalizing cells for potential therapeutic applications. 
Telomerase gene transfer technology, being developed by Geron, could be 
important for the development of compatible, transplantable tissues 
derived from hES cells that result in durable, long lasting grafts. 
Further, hES cells are the earliest, most upstream pluripotential stem 
cells and the only human stem cell thus far shown to self-renew in the 
undifferentiated state. These characteristics provide unique 
capabilities to these cells which, we believe, will likely translate 
into technical and commercial competitive advantages.
    Question. What about differentiated stem cells: are there issued or 
pending patents on these later-stage cells by other companies or 
institutions?
    Answer. There are issued patents and pending patent applications on 
later stage differentiated stem cells and non-primate embryonic stem 
cells held by other companies or institutions. It is possible that 
Geron may determine it advantageous to negotiate a license certain of 
these technologies. However, the human embryonic stem cell occurs 
developmentally upstream from all other stem cells and a broad claim 
covering these cells has already been allowed by the US patent office. 
Importantly, we will also attempt to patent genetically engineered 
downstream cells derived from hES cells. Geron will continue to 
aggressively pursue worldwide protection for this technology and 
subsequent related inventions.
    Question. What about growth and differentiation factors: does Geron 
need to license this technology?
    Answer. Geron may need to in-license certain technologies to enable 
the development of the full therapeutic potential of hES cells, 
including certain vector technologies, genetic differentiation 
technologies, and growth factors. We will attempt to accomplish this 
via licensing agreements and other forms of partnerships.
    Question. Isn't there a business risk that work in this field will 
someday be prohibited by the government?
    Answer. Geron Corporation believes that the potential benefits to 
medicine we have described are enormously important. Geron, and the 
scientific and medical communities, generally support appropriate 
scientific and ethical guidelines for conducting research in the field. 
All product applications will, as is the case for all new therapeutics, 
be carefully evaluated by the FDA. We anticipate that follow-on 
research and development from breakthrough discoveries in science such 
as hES cells will continue to be encouraged.
    Question. Why should any one company be permitted to own the rights 
to something as potentially important and valuable as the hES cell?
    Answer. hES cells that exist outside the body in culture are 
derived by a specific and novel laboratory process, and do not exist in 
nature, so are therefore patentable. Geron will continue to invest in 
product development based on this discovery. Academic researchers will 
also work with the cells to develop other potential therapeutic uses 
for them.
Ethical/Social Issues
    Question. Is it possible that using ES cells will eliminate or 
reduce the need to rely on controversial methods of research?
    Answer. hES cells are expected to provide an immediate source of 
material for the development of cells and tissues for application in 
transplantation therapies. As such, hES cells could help relieve the 
need to continually resource primary human fetal-derived tissues.
    Question. Who should control and regulate the use of this 
technology?
    Answer. The US Food and Drug Administration is the appropriate 
regulatory body to supervise the clinical testing of all therapeutic 
products derived from hES cell technology.
 statement on human embryonic stem cells by the geron ethics advisory 
                                 board
Background
    Human embryonic stem (hES) cells have been derived and subsequently 
maintained in tissue culture. The hES cells are isolated from donated 
preimplantation embryos (technically, from the inner cell mass within 
the blatocyst) produced through In Vitro Fertilization for clinical 
purposes. Institutional Review Boards (IRBs) have approved the 
research. All the cell research is conducted within the guidelines of 
the 1994 report of the NIH embryo research panel and the 1997 National 
Bioethics Advisory Committee report.
    What makes the hES cells unique and important is that they are:
    1. Pluripotent
    2. Self-renewing
    3. Expressive of the enzyme telomerase
    4. Normal in chromosomal structure
    Because of these features, these hES cells have the potential to 
make distinctive contributions to:
    1. Understanding developmental biology (e.g., how tissues 
differentiate)
    2. Pharmaceutical research (e.g., drug discovery and testing)
    3. Transplantation medicine (e.g., generation of heart muscle 
cells, bone marrow, etc.)
    There is no intention to use the hES cell lines for cloning a human 
person, transfer to a uterus (they could not develop into a fetus), or 
generating human-human or human-animal chimeras (mixing cells of 
different individuals or species).
             statement of the geron ethics advisory board:
    An Ethics Advisory Board, whose members represent a variety of 
philosophical and theological traditions with a breadth of experience 
in health care ethics, was created by Geron Corporation in July 1998. 
The Board functions as in independent entity, consulting and giving 
advice to the Corporation on ethical aspects of its work. The process 
of the Board's deliberations has included sessions informing the Board 
of the scientific, technical, and product development work of the 
Corporation. Members of the Board have no financial interest in Geron 
Corporation.
    The Geron Ethics Advisory Board is unanimous in its judgment that 
research on hES cells can be conducted ethically. In order for such 
research to be conducted ethically in the current context, some 
conditions must pertain. In addition, further public discourse will be 
needed on a range of ethically complex questions generated by this 
research.
    1. The blastocyst must be treated with the respect appropriate to 
early human embryonic tissue. Members of the Board are unanimous in 
taking a developmental view of the moral status of the developing human 
being. However, we also hold that, as human tissue, the blastocyst is 
to be treated with moral seriousness. Research use of the blastocyst 
requires justification; that justification is found in research that 
aims ultimately to save or heal human life. This means that such tissue 
is to be used only when there is an overriding good to be derived from 
the research. In the view of the Board, the three purposes of research 
(understanding developmental biology, pharmaceutical research, and 
transplantation medicine) qualify as such goods.
    2. Women/couples donating blastocysts produced in the process of In 
Vitro fertilization must give full and informed consent for the use of 
the blastocysts in research and in the development of cell lines from 
that tissue. The consent process must be undertaken with care, in 
recognition that donors undergoing In Vitro Fertilization are often 
vulnerable. Donors should understand the potential market implications 
of the research, and should be advised as to whether or not there are 
any proprietary rights in the tissue.
    3. The research will not involve any cloning for purposes of human 
reproduction, any transfer to a uterus, or any creation of chimeras.
    4. Acquisition and development of the feeder layer necessary for 
the growth of hES cell lines in vitro must not violate accepted norms 
for human or animal research.
    5. All such research must be done in a context of concern for 
global justice. One of the reasons the Ethics Advisory Board supports 
this research is its potential to contribute to widespread accessible 
medical interventions to alleviate human suffering. Accordingly, in the 
development of this research and its applications, attention must be 
paid to how technologies can be developed and utilized fairly for all 
people.
    6. All such research should be approved by an independent Ethics 
Advisory Board in addition to an Institutional Review Board.
    This analysis applies only to the isolation of hES cells from in 
vitro fertilized blastocysts. The Ethics Advisory Board has not yet 
considered the implication of emerging research on other stem cells 
isolated from fetal tissues.
STATEMENT OF ERIC MESLIN, Ph.D., EXECUTIVE DIRECTOR, 
            NATIONAL BIOETHICS ADVISORY COMMISSION
    Senator Specter. Our final witness on this panel is Dr. 
Eric Meslin, executive director of the National Bioethics 
Advisory Commission, Ph.D. in philosophy from the Kennedy 
Institute of Ethics at Georgetown 1989, authored and coauthored 
some 40 book chapters and articles on bioethics, and is a 
senior research fellow at Georgetown University.
    We appreciate your joining us, Dr. Meslin, and look forward 
to your testimony.
    Dr. Meslin. Thank you very much and good morning, Mr. 
Chairman. I am pleased to appear before you and offer some 
brief remarks on the subject of human stem cell research. Since 
I only learned late yesterday afternoon that I would be 
testifying, with your permission I will submit my written 
testimony for inclusion in the written record soon after this 
hearing is complete.
    Senator Specter. Yes; that would be fine. We appreciate 
your coming. We had called upon the chairman of the commission 
and we did give late notice. When we reviewed our witness list, 
we thought that we ought to hear from you since the President 
had written to you and you had responded. So we thank you for 
coming on short notice.
    Dr. Meslin. My pleasure.
    Mr. Chairman, as you know, on Thursday, November 14, 
President Clinton wrote to Dr. Harold Shapiro, chair of NBAC, 
expressing concern about the report of an apparent experiment 
that involved the fusion of a human cell with a cow egg. The 
President requested that NBAC ``consider the implications of 
such research at your meeting next week and to report back to 
me as soon as possible.'' The President also requested that 
NBAC undertake a thorough review of the issues associated with 
human stem cell research, balancing all ethical and medical 
considerations.
    NBAC met 3 days later on November 17 for a regularly 
scheduled meeting and, in response to the President's first 
request, included on its agenda a discussion of the human cell-
cow egg experiments. I must say that the commission was aided 
in these discussions greatly by consultations via telephone 
with Dr. Ralph Brinster of the University of Pennsylvania. Also 
in attendance at this meeting was Dr. West, from whom you have 
already heard.
    Following the commission's discussions, Dr. Shapiro 
prepared a letter which he sent to President Clinton on 
November 20, a copy of which NBAC has made available to this 
subcommittee and is, I might add, available on our website at 
www.bioethics.gov.
    Mr. Chairman, now that the commission has responded to the 
first of the two requests made in President Clinton's initial 
letter, we are now turning our attention to preparing a 
comprehensive report on the ethical, legal, scientific, and 
medical issues arising from research involving human stem 
cells. We intend to complete this report as quickly as possible 
and very likely by early spring.
    The commission next meets on January 19 and 20 of the 
coming year and we have already decided to devote the majority 
of our meeting to this subject. As with all commission reports, 
we intend to consult widely with the public, with scientists, 
with health professionals, with bioethicists, with industry, 
Government officials, and others who can provide us with the 
benefit of their wisdom.

                           prepared statement

    In particular, NBAC looks forward to working with you and 
your subcommittee in the coming months, and I would be 
delighted to extend my staff's offer to work with your staff 
and to brief them on our work as we seek their input.
    Thank you very much, Mr. Chairman, for the opportunity to 
appear before you this morning.
    Senator Specter. Thank you. Thank you very much, Dr. 
Meslin.
    [The statement follows:]

                  Prepared Statement of Eric M. Meslin

    Good morning Mr. Chairman and distinguished members of this 
subcommittee. My name is Eric Meslin. I am the Executive Director of 
the National Bioethics Advisory Commission, also known as NBAC. I am 
pleased to appear before you this morning and offer some brief remarks 
on the subject of human stem cell research. However, since I only 
learned late yesterday afternoon that I would be testifying, with your 
permission, I will submit my written testimony for inclusion in the 
written record soon after this hearing is complete.
    Mr. Chairman, as you know, on Thursday, November 14, 1998, 
President Clinton wrote to Dr. Harold T. Shapiro, Chair of the National 
Bioethics Advisory Commission, expressing concern about the report of 
an apparent experiment that involved the fusion of a human cell with a 
cow egg. The President requested that NBAC ``consider the implications 
of such research at your meeting next week, and to report back to me as 
soon as possible.'' The President also requested that NBAC ``undertake 
a thorough review of the issues associated with * * * human stem cell 
research, balancing all ethical and medical considerations.'' A 
specific time frame was not given for this latter study.
    NBAC met three days later, on November 17, 1998 for a regularly 
scheduled meeting, and in response to the Presidents first request, 
included on its agenda a discussion of the human cell/cow egg 
experiments. [The Commission was aided in these discussions by 
consultations via telephone with Dr. Ralph Brinster. Also in attendance 
at this meeting was Dr. Michael West, of Advanced Cell Technology, who 
was given an opportunity to answer questions.]
    Following the Commission's discussions Dr. Shapiro prepared a 
letter, which he sent to President Clinton on November 20, 1998, a copy 
of which NBAC has made available to this subcommittee.
    Mr. Chairman, now that the Commission has responded to the first of 
the two requests made in President Clintons letter, we are now turning 
our attention to preparing a comprehensive report on the ethical, 
legal, scientific and medical issues arising from research involving 
human stem cells. We intend to complete this report by late spring 
1999. The Commission next meets on January 19-20, 1999 and will devote 
the majority of our meeting to this subject. As with all Commission 
reports, we intend to consult widely with the public, with scientists, 
health professionals, academics, industry, government officials and 
others who can provide us with the benefit of their wisdom. In 
particular, NBAC looks forward to working with you and your 
subcommittee in the coming months. I would be delighted to work with 
your staff to brief them on our work and seek their input.
    Thank you very much Mr. Chairman for the opportunity to appear 
before you this morning.

                           Fetus destruction

    Senator Specter. Mr. Doerflinger, you stated that the fetus 
destruction should not be geared toward research. If fetal 
material is available, then, in a manner which does not arise 
from being geared toward research, do you find that research 
acceptable?
    Mr. Doerflinger. For Federal funding?
    Senator Specter. Yes.
    Mr. Doerflinger. We do not, though I understand that is the 
current law. I have no reason to believe that Dr. Gearhart's 
experiment would not have qualified under that part of the law 
in terms of obtaining the tissue only after the abortion and 
not getting involved in the informed consent process of the 
woman and so on.
    Senator Specter. Why do you make the distinction, as you 
did in your testimony, that there is a difference, as I 
understood your testimony, where there is fetal destruction 
geared toward research contrasted with fetal destruction which 
is not geared toward research? You think there is a significant 
distinction there?
    Mr. Doerflinger. I think the law recognizes a distinction, 
because it requires that if the tissue research is going to be 
federally funded there cannot be any influence upon the timing, 
manner, or method of the abortion on the part of the 
researcher. This is designed as a way of creating a kind of 
wall of separation between the research on the subsequent 
tissue and the actual abortion.
    We think that wall is rather porous. We believe that when 
Government requisitions tissue from abortions generally it 
collaborates with an industry we do not think it should be 
collaborating with, and it tends to legitimize abortion as a 
way to produce useful material. We also think that the avenues 
for getting these tissues from other sources, such as 
miscarriages and ectopic pregnancies, have not been 
sufficiently explored. The Bush Administration began to fund a 
project in exploring those avenues, but that was shut down by 
the Clinton Administration before it produced any results.
    I think the issue, though, is also raised with regard to 
the use of the stem cell lines from the Wisconsin experiment, 
because even though it does not involve what we would 
ordinarily call an abortion, it does involve destroying embryos 
to get the stem cells. The current fetal tissue law does cover 
embryos as well as fetuses, but it speaks in terms of induced 
abortion instead of in terms of destruction in the laboratory. 
I think that nobody was thinking of this then when they framed 
the law.
    But the question is whether these embryos were destroyed in 
a certain way, in a manner and timing that is geared toward 
producing these cell lines. If that is the case, then does it 
not violate that wall of separation that the Congress was 
trying to create between the motives for destroying the embryo 
and the motives for using the subsequent tissue?
    Senator Specter. Well, I think you raise a very valid point 
when you raise the porous issue if there is a subterfuge here. 
You think there may be some line, as fetal tissue from 
miscarriages where, as you put it, it would not be a porous 
line, but one which could be determined that the fetal tissue 
was not obtained for experimental purposes, but happened in the 
natural course where the fetus could not survive?
    Mr. Doerflinger. Well, that is right. If the tissue is 
available because of death by accident, there is no question of 
mixed motives or collaborating with the decision to destroy. I 
should mention that it is footnoted in my longer statement that 
the National Catholic Bioethics Center did a book-length study 
of this in league with Dr. Maria Macheta of Georgetown 
University and was able to determine that Catholic hospitals 
would be willing to provide the resources for obtaining tissue 
of that kind that is not from induced abortion and of banking 
it so that cell lines could be developed that might be useful 
in these areas.
    Senator Specter. Mr. Doerflinger, you also made a 
distinction between embryos at, I think you said, implantation 
contrasted with pre-implantation. Was that your testimony?
    Mr. Doerflinger. That is a distinction that is in the 
current regulations. The current regulations, the Code of 
Federal Regulations, protects the embryo from implantation 
onward. The effect of the appropriations riders that have been 
in effect for the last 3 years was to extend similar protection 
to the embryo in the laboratory who has not been implanted in 
the womb.
    Senator Specter. Well, that raises the question which Dr. 
Caplan testified to, and I appreciate your view on it, where he 
characterized the situation as tissues to be otherwise 
destroyed or tissues not to become human beings. If you take 
his definition on an embryo, where it is not to become a human 
being and it is to be otherwise destroyed, do you see an 
ethical objection to using the embryo in that circumstance?
    Mr. Doerflinger. Yes; I think the nature of the moral 
argument here--and it is something Congress debated at some 
length in 1995--is because someone else in the private sector 
ultimately plans to discard this embryo, why do we not destroy 
it ourselves? To be quite frank, Mr. Chairman, I think you 
could leave as chairman of this committee and close down the 
committee if that is the basis on which this committee is going 
to make decisions, if you are going to just fund something that 
anybody else in the private sector is going to do anyway.
    But what we think is that when Congress appropriates funds 
it decides there are certain things out there that, even though 
other people are going to do them anyway, we are not going to 
do with the taxpayers money. That is why we have bans on 
abortion funding even though abortion is legal.
    The analogy limps a bit here because in this case two of 
these three experiments I believe would not be legal in your 
home State of Pennsylvania. They would be felonies.
    Senator Specter. Well, this committee or subcommittee is 
not, No. 1, about to close down; No. 2, not about to make 
decisions----
    Mr. Doerflinger. I hope you do not.
    Senator Specter. What we are going to do is ask some 
questions and try to figure some things out. Then, if we think 
we know enough, then we will consider making some decisions.
    Mr. Doerflinger. Could I add one point on that, because it 
is something that came up 3 years ago quite a bit. When the 
effort was made in the congressional debate to protect only 
against the special creation of embryos for research and to 
allow harmful research on so-called spare embryos, we found a 
number of statements from people who run the IVF clinics who 
were willing to say that the distinction was meaningless. 
Basically, if you allow the research on spare embryos, then 
when they do the IVF work, the in vitro fertilization work, 
they will just make more of them up front and make sure that 
they will have spares left after the fact.
    In Australia and the United States, people who run these 
clinics are saying this. So it is an ineffectual distinction to 
make in terms of funding policy, I think.
    Senator Specter. Well, I can understand that, and if you 
are dealing with subterfuges that is something that you have to 
deal with. But before we get to the subterfuge, which I think 
we would all agree is inappropriate what I am trying to get are 
your views on some of the basic points.
    You think that an embryo ought not to be used for research 
even if it is going to be destroyed under circumstances which 
have integrity, where you do not make more than you need or you 
are not having a subterfuge, but there is a genuine 
fertilization issue and embryos have been created and now they 
are not to be used, but are to be destroyed? If that is 
factually true, would you say that in the private sector it is 
unethical to use those embryos for research purposes?
    Mr. Doerflinger. Yes; I do not think the fact that someone 
else plans to mistreat human life creates any moral burden on 
you to go ahead and mistreat that life yourself. I believe that 
that is the principle that Congress has enacted in various ways 
in the course of debates on fetal research.
    Senator Specter. I am making a distinction now between 
public funding and private funding.
    Mr. Doerflinger. I understand.
    Senator Specter. I asked you the question as to private 
funding. Do you think that----
    Mr. Doerflinger. I am just making an ethical point which 
would apply to either.
    Senator Specter. Which would apply to both?
    Mr. Doerflinger. Yes; It seems to me that one of the things 
that Congress did in 1985 to clarify the Federal regulations 
was to say, even if it is crystal clear that someone is 
intending to have an abortion, the fetus that is going to be 
subject to that abortion should not be treated by the 
Government as deserving any less protection from research harm, 
research risk, than an embryo or fetus intended to be carried 
to term.
    So this was a statement of moral principle. People make 
individual decisions out in the private sector. There are times 
when you cannot do anything about that. But even when that 
child has been abandoned by his or her own parents, that does 
not give the Government a moral warrant to go and do harm by 
itself.
    Senator Specter. Thank you very much.
    Senator Harkin.
    Senator Harkin. Thank you very much, Mr. Chairman.
    I want to ask the scientists who are here. Again, I want to 
focus back on the issue that I brought up with the other panel 
initially, and that is whether or not under the reading of the 
ban on embryo or embryo research--you were here, you heard me 
read it. I will read it again. Section 511: ``None of the funds 
made available in this act may be used for the creation of a 
human embryo or embryos for research purposes; research in 
which a human embryo or embryos are destroyed, discarded, or 
knowingly subject to risk of injury or death greater than that 
allowed for research on fetuses in utero under'' other sections 
of the law. ``For purposes of this section, the term human 
embryo or embryos includes any organism, not protected as a 
human subject under 45 CFR 46.''
    I asked all of the scientists who were here before the 
question of whether or not these stem cells are organisms. And 
I believe the record will show they all said no, it is not an 
organism.
    Would that be your view, Dr. Meslin?
    Dr. Meslin. I cannot speak on behalf of the commission 
since we did not deliberate about the ban during the several 
hours that we devoted to our discussion----
    Senator Harkin. You did not go to the law and look at that?
    Dr. Meslin. Not in the 2 hours that we spent deliberating 
in response to the President's request. We considered it as an 
issue that we felt was important to raise in the context of our 
longer study and we intend to look at that very carefully in 
the coming months.
    Senator Harkin. Dr. Okarma.
    Dr. Okarma. My view is that these cells are clearly not 
organisms. They are highly derived by a laboratory process that 
took years to develop, and, in fact, as we have said, are not 
the cellular equivalent of an embryo. Were these cells to be 
implanted, they would not form a conceptus nor develop.
    Senator Harkin. Dr. Caplan.
    Dr. Caplan. Absolutely not an organism. Stem cells lack the 
capacity to become viable, independent, interrelated, 
functioning entities, so they are not organisms.
    Senator Harkin. Let me ask the nonscientist. Mr. 
Doerflinger?
    Mr. Doerflinger. Thank you. Stem cells are not organisms. 
However, two of the three experiments that were discussed here 
were not experiments on stem cells. They were experiments to 
get stem cells, by in one case creating and then destroying 
embryos, organisms, and in the other case taking embryos 
already in existence and destroying them.
    In the Gearhart experiment, the question is whether what he 
has created in that tissue culture is only stem cells or in 
some cases is organized enough to be an embryo. He says in his 
study that these bodies in the tissue were forming ``complex 
structures closely resembling an embryo during early 
development,'' and that ``they appear to recapitulate the 
normal developmental processes of early embryonic stages.''
    So I think that it is an open question with regard to Dr. 
Gearhart's experiment whether in the course of this experiment 
he is actually creating some early embryos in the culture. I 
think the answer is no, but I do not know and I do not know 
that anyone knows.
    The other experiments clearly involve the laboratory 
manipulation and destruction of human embryos, which are 
protected organisms.
    Senator Harkin. What was that last thing you said? The 
other ones are not?
    Mr. Doerflinger. The other two experiments, the 
Massachusetts and Wisconsin experiments, clearly involve the 
destruction of human embryos, which are organisms, in order to 
obtain from them stem cells, which are not organisms.
    Senator Harkin. I did not think that was true of the 
Massachusetts.
    Dr. Caplan. I do not think it is true, either, in the sense 
in which----
    Senator Harkin. It was not true. Mr. Doerflinger, you may 
be closer on the other one, but certainly not Massachusetts.
    Mr. Doerflinger. Massachusetts, because it is a cow cell?
    Senator Harkin. No, no, no.
    Mr. Doerflinger. I could cite you----
    Senator Harkin. Dr. West, where did you get your cell from, 
your stem cell? Was it from an embryo?
    Dr. West. Well, it was from an aggregation. It was the 
product of somatic cell nuclear transfer, creating a small 
group of cells. Its status as an embryo would be a matter of 
debate. I think it is impossible to answer at this point.
    Mr. Doerflinger. I think it has been answered. We have a 
fact sheet which I would be happy to append to my testimony, in 
which most of the leading scientists involved in somatic cell 
nuclear transfer say that when you put a somatic cell nucleus, 
properly prepared, into an enucleated egg what you produce is 
an embryo. It is only because it produces an embryo that we are 
here debating human cloning at all.
    Dr. Caplan. Just as a quick comment about what is in the 
dish, which is what we are talking about now, it would be 
optimistic for anybody to say that what was created in the 
Massachusetts report, No. 1, is not published; No. 2, is not 
verified. But more to the point, we do not know actually what 
the capacity or what will happen if that particular creation or 
construct, if someone attempted to grow it out.
    When I was testifying before, I suggested that humility 
rather than bright lines might be what we want to bring to this 
discussion. It is possible that someone in Massachusetts could 
culture out something from what was in that dish. We have no 
idea.
    Senator Harkin. It seems to me, then, that looking back on 
where we have been on fetal tissue research, which was banned 
for a number of years and then it was lifted. We had the ban 
and then it became I think clear to a lot of us in the Congress 
and in the administration and in the scientific community--I 
heard for years about the problems that this ban was causing.
    So we lifted the ban, but we replaced it with very strong 
Federal guidelines. So maybe that is what we are looking at 
here--not a ban but putting down strict guidelines as to what 
can be done with this.
    Dr. Caplan. If you were headed in my direction, I would say 
it does seem to me that the two key moral categories of what we 
are talking about this morning are what are the sources of stem 
cells and where do they come from. There are issues there about 
the use of embryos. I tried to suggest in my oral and written 
testimony that it is wrong to say that all embryos are alike.
    I will repeat what Senator Specter drew out of my 
testimony: It does not seem to me ethically sound to treat 
embryos destined for destruction, that no one wants to use, or 
embryos derived from tissues that have already been destroyed, 
from fetal gametes, as on a par with specially created human 
embryos at the IVF clinic that you intend to make a baby from. 
I do not believe the same moral framework ought to be applied 
there.
    It does seem to me that if we want to understand how best 
to responsibly use stem cell research technology, the more 
public, the more accountable, the more oversight we have got, 
that is the way we are going to be able to make the judgments. 
If we let it just stay private, not only will it be slow, it 
will be hidden, it will be secret, and we will not know what 
people are doing with these materials. I think that is not the 
desirable outcome from a public policy point of view.
    Mr. Doerflinger. I do not know, if I can respond to that 
question as well. I think guidelines may be appropriate in 
cases where you are dealing with tissue that is already tissue, 
it is already from someone who is already dead. What they are 
talking about is setting guidelines for how and when to make 
and destroy human embryos, and I do not think guidelines alone 
are sufficient for that.
    I just want to note that in Dr. West's testimony he said 
that the purpose of his experiment is to allow for ``the 
production of a blastocyst-staged embryo genetically identical 
to the patient who donated the nucleus, which then is harvested 
for its stem cells.'' If you ask are the stem cells an 
organism, the answer is no. If you take my heart out, it is not 
an organism, either. But the question is the experiment 
involves ripping out the cells from what was before a living 
organism.
    Senator Harkin. Well, we can go into this for a long time. 
The fact is is that we have thousands of embryos now all over 
the United States that are frozen in nitrogen and they are 
obviously going to be destroyed. Let us face it, OK. You are 
not going to keep them forever and ever and ever.
    So if there is a potential of getting the stem cells from 
those and using those for the research, what is wrong with 
that? Why should we not?
    Dr. Caplan. It is not actually thousands; it is tens of 
thousands.
    Senator Harkin. I do not know how many.
    Dr. Caplan. They seem to be wards of the utility company at 
this point, as long as the electricity holds out.
    Senator Harkin. If these stem cells are indeed--I do not 
know what the proper word--self-replicating, they can keep 
growing----
    Dr. Caplan. Immortal, immortal.
    Senator Harkin. Immortal. Then it would seem to me that we 
already have, Mr. Doerflinger, a source that is already going 
to be destroyed, that were not produced for this purpose 
because this purpose did not exist before.
    Dr. Caplan. Senator, just to add two points about that. 
One, these are embryos that were not created with any eye 
toward exploitation of research.
    Senator Harkin. Exactly, exactly.
    Dr. Caplan. And I have talked before coming here today with 
as many in vitro fertilization clinic personnel as I could, and 
they say that after a prolonged period of time, say 4 or 5 
years, they are not going to use these embryos. They do believe 
there is a diminishment in their ability to become anything. So 
not only are we talking about embryos that are fated not to be 
put into any human being, we are talking embryos that 
specialists would not use in any human being.
    So it does seem to me again morally a different status 
applies here. I know we have debated this in the past and will 
undoubtedly revisit it again, but I want to say it does seem to 
me that that source for stem cells is very different from a 
specially created circumstance where we head out to make them 
to use them.
    Senator Harkin. This may be a topic for another hearing, 
Mr. Chairman, and I know you want to wrap this up.
    There is one other area, I am just going to make a 
statement on it, but I believe it is going to really compel us, 
Mr. Chairman, to have some further hearings on this. It has not 
to do with ethical and moral implications of what we are doing 
here. It has to do with the legal implications, of patent laws.
    The article in the Post this morning pointed out that, even 
if Congress resolves the ethical issues, there is a dispute 
over patents. I notice that in your testimony, Dr. Okarma, you 
talked about Geron's intellectual property position, saying 
that:'' Geron's intellectual property estate in the embryonic 
stem cell field consists of ''--dah-dah-dah-- ``a worldwide 
license to the stem cell patent estate of Dr. John Gearhart and 
the Johns Hopkins University. This license includes all 
applications of human embryonic stem cells, including 
diagnostic and therapeutic products.''
    Whew, man. I take a little issue with that one. You may not 
think so, and again this may take us a whole other hour and we 
do not have the time.
    Senator Specter. Senator Harkin, you may be about to start 
a subsequent hearing.
    Senator Harkin. Well, I think, Mr. Chairman, we are going 
to have to have a hearing on this.
    Senator Specter. Well, I think there are many questions 
which we cannot answer in the parameter of a 2-hour hearing, 
and we had targeted conclusion for 11:30 a.m., which is just 2 
minutes away.
    Senator Harkin. I just wanted to throw it out there.
    Dr. Okarma. May I have the courtesy of a response?
    Senator Harkin. Pardon?
    Dr. Okarma. May I have the courtesy of a response?
    Senator Harkin. Sure.
    Dr. Okarma. First of all, as you may know, the bulk of 
patent applications, for example, in new gene sequences come 
not from the industry, but from academia, academic centers. 
Like that, the applications that we have taken license to were 
originated by Johns Hopkins and University of Wisconsin.
    In terms of the exclusivity and the applications issue that 
you raised, this is a starting point. We recognize that Geron 
by itself could never commercialize all of the opportunities we 
have heard elegantly testified to today. So it is our 
commercial intent to create partnerships with other companies 
to further the development of these life-saving applications.
    Furthermore, if I may use what we have done with our 
telomerase discovery in January of this year, where we 
published in Science the ability to immortalize cells, since 
that publication we have received and responded to over 250 
requests from laboratories around the world to receive that 
gene, which we have sent to them and allowed, under appropriate 
constraining guidelines, the kind of work that could be funded, 
is funded by the NIH in cellular immortalization. And we would 
propose to perform the same kind of academic collaboration with 
these cells were they fundable by the NIH.
    Senator Specter. Thank you very much for that answer, Dr. 
Okarma.
    Senator Harkin. We need another hearing.
    Senator Specter. Senator Harkin suggests another hearing 
and I think there is a need for further hearings on this issue 
and others. We are on a very, very deep and complex subject and 
in the course of the 2 hours we cannot cover it totally.
    I just want to cover one more point with you, Dr. Okarma, 
and that is your view on the importance of having NIH be free 
to engage in this kind of research. Is the private sector, 
illustrated by your company, sufficient to undertake this 
research, or do you think it is desirable to have NIH involved 
as well?
    Dr. Okarma. It is imperative, essential, that the NIH be 
involved in the development of these applications.
    Senator Harkin. We have Mr. Doerflinger's view on that. Dr. 
Caplan, what is your view on the issue of having NIH involved?
    Dr. Caplan. If the NIH is not involved, the research will 
go more slowly, the research will be driven solely by 
commercial practicality, the patent policies will be locked 
down on basic science, which should not happen, and there will 
be very little accountability. The substitute virtue will be 
secrecy. I think it would not be sound public policy.
    Senator Specter. Dr. Meslin, do you care to offer an 
opinion on that subject?
    Dr. Meslin. My own view is that it is absolutely essential 
that NIH play a leading role. They have been thinking about 
ethical issues as well as the scientific issues for many years, 
and we are anxious to get their views as we deliberate on our 
own report.
    Senator Specter. Mr. Doerflinger, I think you have 
expressed yourself on this, but I want to give you an 
opportunity to comment further, and perhaps with some focus on 
the question which I do not think you have addressed, raised by 
others, about the desirability of having regulations and 
oversight, which you do not have with the private companies, 
although we could legislate that as well. Would you care to 
supplement your views on the question of NIH involvement?
    Mr. Doerflinger. I think funding and regulation are often 
very appropriate to distinguish acceptable research from 
possible abuses. My problem with some of the experiments 
discussed here is that I believe they are themselves the 
abuses, so I do not see any point in funding them in order to 
regulate how they are done.
    I think the argument about it being done in secrecy would a 
fortiori apply to the fact that in eight or nine States, as I 
mentioned earlier including Pennsylvania, they are illegal 
already anyway. So I suppose there would be an argument for 
also dropping all of those criminal statutes against 
experimenting on embryos, but I do not think that is going to 
be convincing to those who think that these statutes are really 
protecting human life.

Prepared statement of Daniel Perry, on behalf of the Alliance for Aging 
                                Research

    We have received a statement from Daniel Perry, on behalf 
of the Alliance for Aging Research, it will be inserted into 
the record at this point.
    [The statement follows:]
                   Prepared Statement of Daniel Perry
    Chairman Specter, Senator Harkin and Members of the Committee: 
Thank you for the opportunity to address the matter of embryonic stem 
cell research. As the head of a not-for-profit group eager to find 
cures and preventions for the diseases of aging and overall better 
health and vitality for the elderly, my views on research are dictated 
by the medical needs of the growing population of older Americans. The 
Alliance for Aging Research, which I represent, works to stimulate 
academic, governmental and privately sponsored research into the 
chronic diseases of human aging. I am here to express the Alliance's 
view that any legislation which stops or restricts stem cell research 
could seriously impede highly promising research which will greatly 
benefit older Americans, their families and the nation as a whole.
    The United States and much of the world is experiencing a profound 
and wholly unprecedented demographic shift toward greater longevity for 
human beings. Every day in our nation another 6,000 people celebrate a 
65th birthday and America's Baby Boomers are entering their 50s in even 
greater numbers.
    In the decade between ages 50 to 60, the risks to the average 
person of being diagnosed with hypertension, arthritis or diabetes more 
than triple. Over the next 30 years, the United States population over 
age 65 will double to at least 70 million people. Their risks to 
disease including cancer, stroke, macular degeneration, Parkinson's and 
Alzheimer's diseases are doubling every five years. The cost of these 
disorders--just in purely economic terms--is staggering. If you add up 
the costs of eight of the major diseases of aging--osteoporosis, 
stroke, depression, arthritis, Alzheimer's, diabetes, cancer and heart 
disease--the total is $573 billion annually. Only new discoveries from 
biomedical research hold the hope of delaying or preventing altogether 
these debilitating conditions, potentially saving the nation billions 
of dollars.
    Unless scientists discover better ways to treat, postpone and 
possibly prevent such disabling conditions, the burden on Medicare and 
private insurance will be crushing as the Baby Boom generation moves 
into the high-risk years. Without research breakthroughs and their 
applications, we will be left with the equivalent of very expensive 
hand holding for sick older people. In truth, today's drugs and other 
remedies for age-related diseases are not good enough. Even the better 
versions of current pharmaceuticals are designed to treat only the 
symptoms of heart failure, arthritis, and cancer, not the root causes.
    The good news is that there are signs of an historic shift in drug 
development. Advances in genetics research are taking us towards 
personalized medicines that exactly match each person's unique needs 
and biochemical profile. Personalized medications would be far more 
effective in promoting health, and far less likely to carry side 
effects and complications that too often make matters worse, not 
better, for older people.
    Part of the revolution in drug discovery is that some of the 
largest pharmaceutical companies are ready to invest billions to 
produce drugs that work by postponing the onset of diseases, or prevent 
them entirely by shutting off their genetics switches. This has 
enormous potential for the geriatric population. Even a brief delay in 
the onset of age-related disability can translate into dramatic savings 
for the economy and for the nation. For example, we estimate that 
postponing physical dependency among older American by just one month 
would save the U.S. at least $5 billion a year in health care and 
nursing home costs. Postponing the average onset of Alzheimer's disease 
by just five years would eventually save $50 billion a year in health 
care costs by eliminating half of all cases of that disease.
    With emerging research, there is now good reason to hope that 
scientific understanding may some day permit new approaches to 
disabilities driven by the aging process itself. As the committee 
knows, earlier this month at the University of Wisconsin, researchers 
reported they had successfully derived human embryonic stem cells with 
the potential to be transplanted into any part of the body for 
therapeutic use. The Wisconsin researchers believe these cells have the 
potential to supply unlimited quantities of normal cells of virtually 
any tissue type. The unique qualities of human embryonic stem cells 
will give researchers powerful new tools to understand mechanisms of 
cell division and cell repair.
    The long range benefit of this kind of research is not the unlikely 
possibility of greatly extended lifetimes, but the plausible use of 
this technology to restore damaged tissues, using self-renewing, 
plenipotent human cells to treat blindness, coronary artery damage, 
diabetes, and other diseases. The ability to maintain long-lived 
colonies of human cells could lead directly to cell transplantation 
techniques in a few years to treat Parkinson's, breast cancer, heart 
disease, and possibly even Alzheimer's disease. Scientists involved in 
this research say that embryonic stem cell technology has the potential 
to be used to generate an unlimited supply of healthy cells and tissues 
for repair or replacement in a vast range of medical uses. To deny our 
aging population the opportunity to benefit from this research would be 
a tragic reversal of dramatic recent biomedical progress toward 
permanent cure of diseases that compromise quality of life and which 
account for so much of our nation's health care expenditures.
    At the Alliance for Aging Research, we view recent advances in 
human stem cell research as a major step toward development of ``gero-
technology.'' Gero-tech is medical science harnessing the mechanics of 
the aging process itself in order to develop novel processes and 
therapies. Ultimately these research techniques could help cure, 
postpone or prevent age-related diseases. The more we learn about the 
mechanisms of aging and the more scientific interest that goes to 
aging, more new discoveries will be made that could improve the health 
and functional independence of older Americans. It would be unwise to 
put barriers in the way of such research.
    The Alliance supports responsible and sound biomedical research, 
including emerging cellular technologies, that could lead to the 
development of therapies for scores of age-related diseases and 
disabilities. At this very moment millions of older Americans are 
suffering from Alzheimer's, Parkinson's, cancer, diabetes and other 
chronic health problems of aging. Not only are they suffering, but 
their families and care givers are suffering too, and hoping that 
scientists will find cures for these devastating disease and other 
conditions while there is still time.
    Our chances of finding new ways to prevent and cure debilitating 
diseases will stifled unless bio-medical research into aging matters, 
including stem cell research, is allowed to proceed without hindrance. 
Certainly, policymakers, ethicists, scientists and patient groups must 
discuss and debate, but in the end, it is important that we arrive at 
public policies that allows stem cell and other promising biomedical 
research to go forward.
    Mr. Chairman, it is likely we will continue to be confronted with 
scientific advances that pose difficult social and ethical questions. 
The vast majority of Americans strongly support the advancement of 
biomedical research through the application of their tax dollars. 
Indeed, surveys consistently show the American people want to see even 
greater efforts against serious and life-threatening diseases. The 
present momentum in the life sciences, and the profound implications of 
what we are learning, will inevitably raise public concerns.
    It is entirely appropriate that as the legislative body which 
appropriates much of the funds for medical research, and as the forum 
for debate over public issues, the Congress exercise its right and 
responsibility to set public policies concerning medical research. 
Surely, Congress is at its best when its actions are informed and 
enriched by slow and careful debate, by advice from expert sources, and 
when taken in respect for minority opinion.
    In the case of proposals to limit any of the tools for scientific 
and medical research, the need for prudence is powerful, due to the 
complexity of the issues and the consequences for public health and 
well-being. Ultimately, however, I believe that it is far better for 
the Congress and the rest of the federal government to maintain an 
constructive role in the ongoing research, rather than taking any 
action which seeks to block it. Only in this way, can the Congress 
ensure that the views of the American people are heeded in the research 
process.
    On this point, it is worth noting that the research on stem cell 
development was carried out in the private sector without any federal 
funds and without any federal involvement or oversight. It is likely 
that private interest in, and support for, this research will proceed 
ahead. We believe the federal government should be actively supporting 
and advancing research that hold promise for healthier aging, including 
the stem cell and related technologies. That support should include the 
development of guidelines by the appropriate federal agencies to assure 
the ethical conduct of this sensitive but important research.
    Mr. Chairman, on behalf of the Alliance for Aging Research, I thank 
the committee for its consideration of this vital issue and for the 
opportunity to present the Alliance's views on it.

                          subcommittee recess

    Senator Specter. Thank you all very much for being here, 
the subcommittee will stand in recess.
    [Whereupon, at 11:32 a.m., Wednesday, December 2, the 
subcommittee was recessed, to reconvene subject to the call of 
the Chair.]


                           STEM CELL RESEARCH

                              ----------                              


                       TUESDAY, JANUARY 12, 1999

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9 a.m., in room SD-192, Dirksen 
Senate Office Building, Hon. Arlen Specter (chairman) 
presiding.
    Present: Senators Specter and Harkin.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENT OF MARIA FREIRE, Ph.D., DIRECTOR, OFFICE OF 
            TECHNOLOGY TRANSFER

                         DEPARTMENT OF COMMERCE

STATEMENT OF Q. TODD DICKINSON, J.D., ACTING ASSISTANT 
            SECRETARY OF COMMERCE, AND ACTING 
            COMMISSIONER OF PATENTS AND TRADEMARKS

                Opening remarks of senator arlen specter

    Senator Specter. Good morning, ladies and gentlemen. The 
hour of 9 a.m., having arrived we will proceed with the hearing 
of the Appropriations Subcommittee on Labor, Health and Human 
Services, and Education.
    Today we are going to move forward with the second hearing 
on the issue of stem cells, focusing on the provision of law 
which appears to bar the National Institute of Health from 
engaging in embryo research.
    We held our first hearing on December 2, and today we are 
going to move ahead with the patent aspects of the issue and 
more testimony on the potential of stem cell research.
    We regret the scheduling difficulties, where we have been 
constrained to make some adjustments because of the Senate's 
consideration of the impeachment issue, and today's hearing had 
been set for 9:30 a.m., but yesterday Senator Lott scheduled a 
meeting at 10 o'clock which made it desirable to move the 
hearing to 9 a.m., this morning, and we are going to do our 
best to conclude by 10 o'clock.
    The focus of our hearing today will center on a number of 
issues. One of them is whether stem cells are defined as an end 
product, which may be the contention of the companies who seek 
patent protection, contrasted with a classification of stem 
cells as a research tool, which would be a designation to 
promote freer dissemination among researchers.
    I am a little disappointed that the Geron Corp., declined 
to testify today, and a number of other major associations have 
considered it too soon to come forward at this hearing because 
their public policy committees have not yet taken a position on 
stem cell research. It is my hope that we might move 
legislation to lift the ban at a very early stage because of 
the urgency involved here with the potential for stem cell 
research, which deals with so many serious diseases.
    I think every day that we lose on lifting the NIH ban costs 
lives, perhaps every hour that we lose costs lives, so I want 
to see if we cannot move this legislation. That is why we held 
the hearing in December, shortly after the research discoveries 
were announced, moving ahead at this early date to be ready, 
and the Congress moves to the legislative agenda.
    I want to now call our first panel, Dr. Maria Freire, 
Director of the Office of Technology Transfer at NIH, and Mr. 
Todd Dickinson, Acting Commissioner of Patents and Trademarks, 
if you would step forward.
    Dr. Freire is the Director of the Office of Technology 
Transfer for NIH, and oversees the patenting and licensing 
activities for NIH and the development and implementation of 
technology transfer policies and procedures.
    She received her Ph.D., in biophysics at the University of 
Virginia. Full statements will be made a part of the record. We 
are going to observe the 5-minute rule to allow the maximum 
amount of time for questions and answers. Thank you for joining 
us, Dr. Freire, and the floor is yours.

                   Summary statement of maria freire

    Dr. Freire. Good morning, Mr. Chairman. I appreciate the 
opportunity of being here today, and I am here to address how 
intellectual property considerations affect basic science and 
the future development of products for public benefit.
    This morning I will focus on three issues, first how 
technology is transferred from the not-for-profit to the 
private sector, second, how this applies to stem cells and stem 
cell technology, and third, the implications for basic 
research.

                    Technology transfer legislation

    Let me start briefly by describing two laws enacted 20 
years ago that encourage universities and Government 
laboratories to commercialize their research. These laws are 
the Bayh-Dole Act and the Stevenson-Wydler Act, including one 
of its amendments, the Technology Transfer Act. In general, 
these laws allow the laboratories and the recipients of 
Government funding to elect title to their inventions. They 
also impose certain obligations, to promote utilization, to 
encourage commercialization, and to ensure public availability.
    In the biomedical arena, the impact of these statutes has 
been, indeed, dramatic, and many experts believe that it is the 
close relationship between the academic sector and the private 
sector that has spawned the biotechnology industry. Value to 
the public is also very important as new drugs, vaccines, 
diagnostics, and medical devices of course result from this 
close interaction.
    These activities have also stimulated economic development, 
and they have generated jobs in the United States.
    The University of Wisconsin provides a very good example of 
how the Bayh-Dole Act is implemented. Early work by Dr. Thomson 
on nonhuman primates, such as rhesus monkeys, was federally 
funded. In accordance with the law, the invention was disclosed 
by the university to the NIH, the university filed a patent 
application, and the technology was licensed to a small 
company.
    Because Federal funds were used, the Government has a 
nonexclusive royalty-free right to use patented cells by or on 
behalf of the Government. This allows Government laboratories 
and their contractors the right to use patented cells for 
further research.
    In contrast, when research is funded entirely by the 
private sector, as is the case of Dr. Gearhart's work, the 
Government has no license, and it is strictly a private matter 
whether and under what terms new intellectual property is made 
available to others.

                             Research tools

    Let me point out that the fact that there exists a patent 
is usually not what raises concerns in the biomedical community 
but, rather, it is the way the patent holder chooses to 
exercise his or her rights on the patent.
    For example, the discovery may be a research tool or a new 
procedure, primarily useful as a means to conduct further 
research. Such discoveries are commonly known as research 
tools. These tools may be patentable and, indeed, they have 
economic value for the holder of the patent.
    In our view, however, the value to society is greatest when 
research tools are made widely available to scientists. But, 
therein lies the quandary. What is a research tool to one is a 
product to another.
    Those of us working in this field strive to promote the 
balance between commercial interests and the public interest. 
For example, research tools can also be therapeutic products. 
Licenses can be crafted by scope and field to allow research 
uses without destroying commercial incentives.
    The NIH, indeed, has been concerned with this issue for a 
good while, and Dr. Varmus put in place a national work group 
to study the issue and make recommendations. We will set forth 
guidelines for public comment in February in the Federal 
Register.
    So how does this relate to the pluripotent stem cells? Stem 
cells are research tools today, and hopefully they will also be 
developed into therapeutic products in the future. We 
understand that both Johns Hopkins and Wisconsin licenses to 
Geron are exclusive at this time, but may allow for use of 
these cells by nonprofit researchers under certain terms and 
conditions.
    There is no direct role of the NIH in these negotiations 
and these agreements. However, it is our view that these 
licenses can be crafted to ensure commercial and research 
purposes be both preserved.

                           prepared statement

    For example, licenses can be crafted nonexclusively and 
they should be negotiated whenever possible to allow and assure 
that the research tools are available for researchers as well 
as preserve the commercial applications. It is important to 
reiterate, however, that when only private funding is involved 
the NIH has very little ability to obligate the universities to 
abide by these guidelines.
    Mr. Chairman, I would be pleased to answer any questions.
    Senator Specter. Thank you very much, Dr. Freire.
    [The statement follows:]
              Prepared Statement of Maria C. Freire, Ph.D.
    Mr. Chairman and members of the subcommittee, I am Maria Freire, 
Director of the Office of Technology Transfer at the National 
Institutes of Health (NIH). I am pleased to appear before you today to 
address how intellectual property considerations affect basic science 
and the future development of products for public benefit.
    I understand that the subcommittee is particularly interested in 
how patent rights and commercialization strategies operate in the 
context of the recent findings on pluripotent stem cells reported by 
Drs. John Gearhart from Johns Hopkins University and James Thomson from 
the University of Wisconsin. You have previously heard from a panel of 
experts, including the Director of NIH, Dr. Harold Varmus, on the 
scientific implications of these findings. Given the complexity of 
these issues, it is important to understand how the transfer of 
federally funded technology from the not-for-profit sector--be it 
university or Federal laboratory--to the private sector, is 
accomplished. To do so, I direct you to the successful process 
established by Congress in the 1980's that governs the 
commercialization of federally funded biomedical research.
The Bayh-Dole Act, Stevenson-Wydler Technology Innovation Act of 1980, 
        and amendments, including the Federal Technology Transfer Act 
        of 1986 (FTTA)
    Nearly twenty years ago, Congress enacted a series of laws that 
encourage government owned and government funded research laboratories 
to pursue the commercialization of the results of their research. These 
laws are the Bayh-Dole Act of 1980, the Stevenson-Wydler Innovation Act 
of 1980, including one of its amendments, the Federal Technology 
Transfer Act of 1986 (FTTA). The Bayh-Dole Act addresses intellectual 
property rights in federally funded grants, contracts and cooperative 
agreements, while Stevenson-Wydler and the FTTA address intellectual 
property of government laboratories. The goal of these laws is to 
promote economic development, enhance U.S. competitiveness and benefit 
the public by encouraging the commercialization of technologies that 
might otherwise not be developed into products due to the lack of 
incentives. Generally, these laws allow government laboratories and the 
recipients of government funding to elect to retain title to their 
inventions. They also impose certain obligations: promoting 
utilization, encouraging commercialization and ensuring public 
availability of these technologies.
    I am pleased to say that these goals have been achieved and 
expectations have been surpassed. Indeed, in the biomedical arena, the 
impact of these statutes has been dramatic. Many experts believe that 
the biotechnology industry was spawned from the close interaction 
between academia and industry. The Bayh-Dole Act and the FTTA continue 
to contribute to the global leadership of the U.S. biomedical 
enterprise. New products developed under this system benefit patients 
daily and provide hundreds of scientists with the tools required for 
further discovery in support of our public health mission. The NIH 
intramural program alone has over 150 products on the market, including 
diagnostic kits, vaccines, therapeutic drugs and dozens of antibodies, 
cell lines and other research tools. Statistics on the remarkable 
success of university-based technology transfer activities are also 
available and I have submitted a recent survey for the record.
    To accomplish the transfer of technology, universities have relied 
on authorities granted to them by the Bayh-Dole Act. The Act permits 
the grantee to retain title to intellectual property developed with 
federal funds and to license its rights to for-profit entities. Patents 
provide the right to exclude others from making, using, or selling a 
new invention for the life of the patent. This is society's reward to 
the owner for teaching others how to make and use the invention claimed 
in the patent. In the biomedical field, patents are extremely valuable 
to companies, particularly small companies. They provide a means of 
securing investment income by establishing the company's preeminence in 
a particular area of technology. Parties interested in practicing an 
invention, in which they have no ownership, may obtain rights to the 
invention by entering into a licensing agreement with the patent owner. 
A license is a contract with binding commitments on each party, usually 
involving compensation. A license does not grant title to the 
invention. Licenses can be exclusive, when only one party is permitted 
to benefit from the use of the technology, or non-exclusive, when more 
than one party is allowed to benefit from such rights.
    As this subcommittee well knows, new drugs and vaccines are costly 
to develop; companies will not invest in further research and 
development without some promise of future product exclusivity. When 
Congress gave federal grantees the ability to patent and exclusively 
license government-funded inventions, the private sector turned its 
attention toward publicly supported research as a new source of 
potential products. The value to the public resides in the generation 
of new drugs, vaccines, and medical devices. These activities have also 
stimulated economic development and the creation of new jobs in the 
United States.
    The University of Wisconsin provides us with a good example of how 
the Bayh-Dole Act is implemented. Early work by Dr. Thomson on non-
human primates, such as Rhesus monkeys, was federally funded and 
therefore, the patent obtained on stem cells arising from this work is 
governed by this Act. In accordance with the law, the invention was 
disclosed to the NIH, a patent application was filed by the University, 
through the Wisconsin Alumni Research Foundation (WARF), and WARF 
licensed the technology to a small company (Geron). Because federal 
funds were used for this non-human primate work, the government has a 
non-exclusive, royalty-free right to use the patented cells by or on 
behalf of the government. This would allow the government laboratories 
and contractors the right to use the patented cells for further 
research. In addition, in handling this invention the University must 
ensure that the goals of the Bayh-Dole Act--utilization, 
commercialization, and public availability--are implemented.
    When research is funded entirely by the private sector, the 
government has no license, and it is strictly a private matter whether, 
and under what terms, new intellectual property is made available to 
others for commercial or research purposes. This is the case for the 
Geron sponsored work conducted by Dr. Gearhart on human pluripotent 
stem cells derived from fetuses.
    It is usually not the existence of a patent that raises concern for 
the biomedical research community. The concern arises when the patent 
holder chooses to exercise its rights through licensing in a manner 
inconsistent with the advancement of basic research. For example, many 
new inventions are not final products. The discovery may be a research 
material or a new method or procedure, primarily useful as the means to 
conduct further research. Such discoveries are commonly known as 
research tools. There is little doubt that these research tools may be 
patentable and that they are of economic value to the holder of these 
rights. There is also little doubt that the value to society is 
greatest when such research tools are widely available to scientists.
    Mr. Chairman, I cannot emphasize this point strongly enough. 
Preserving research uses is extremely important to the advancement of 
science. A license that provides complete exclusivity to a technology 
that is also a research tool may result in some product development in 
the short-term, but it will close off opportunities to advance science 
and develop other products in the long-term. The only way to maximize 
the benefit to the public is to ensure that both research use and the 
potential for commercial development are preserved.
    The professionals working in the specialized field of biomedical 
licensing strive to promote a balance between commercial interests and 
the public interest. In those instances where a research tool can also 
become a therapeutic product, licenses can be, and are, carefully 
crafted by scope, application and field to allow use by the research 
community without destroying a company's commercial incentive to 
develop the product. Careful licensing that preserves this balance, 
however, has not always been the case. The NIH has been concerned for 
some time about the potential adverse effects of restrictive licensing 
practices on access to research tools. Dr. Varmus convened a national 
workgroup to study the issue and make recommendations to the NIH. The 
report of the workgroup is on the NIH web site (www.nih.gov./news/
researchtools/index.htm), and NIH expects to publish guidelines for NIH 
supported investigators this spring, in accordance with the report.
Stem Cell Research
    How does this relate to pluripotent stem cells? Pluripotent stem 
cells provide the research community a springboard to launch numerous 
inquiries into the most fundamental processes of cellular growth and 
differentiation that underlie human development. Elucidating these 
mechanisms provides the foundation for the next generation of 
biomedical discovery. Such discoveries will be directed toward 
treatment of human developmental abnormalities, regulation of 
uncontrolled cellular growth associated with cancer, a source of 
differentiated cells and tissues for transplantation therapy, and a 
means to identify new drug targets and test potential therapeutics, 
among others. Realizing the fullest potential from this new stem cell 
technology for the American people deserves and requires further 
inquiry.
    Stem cells are a research tool today; hopefully, they will also be 
developed into therapeutic products in the future. The issuance of 
patents on these new discoveries by the Patent and Trademark Office may 
not necessarily have an adverse effect on continuing research, provided 
that the patent owners devise a licensing strategy that will allow 
basic research to continue unencumbered while preserving commercial 
value. We understand that both the Johns Hopkins and Wisconsin licenses 
to Geron are exclusive at this time, but may allow for the use of these 
cells by non-profit researchers under certain terms and conditions. 
These terms and conditions would be set forth in an agreement commonly 
called a Material Transfer Agreement, or MTA.
    MTAs are vehicles used to transfer proprietary materials between 
and among the for-profit and not-for-profit sectors. While most MTAs 
are simple, 1- to 2-page agreements, MTAs can sometimes pose problems 
due to the type of obligations or restrictions imposed by the provider 
of a material on the recipient. Such obligations can stifle the broad 
dissemination of new discoveries, slow the technology transfer process 
and limit future avenues of research and product development. Examples 
of such obligations include so-called ``reach-through'' provisions that 
may: (1) give the provider of a material ownership of new inventions 
developed by the recipient; (2) require royalty payments by the 
recipient to the provider on inventions discovered by the recipient 
that are not covered by the provider's patent; or, (3) require options 
to exclusive rights to any new intellectual property arising from 
recipient's use of the material. The NIH has minimal authority with 
regard to the stem cell patent and patent applications at issue today, 
and it would be inappropriate for me to try to comment on specific 
terms and conditions that may be imposed by these parties under the 
MTAs contemplated.
    At NIH, our view is that conditions imposed by patent owners--
whether in a license or an MTA--can be crafted to ensure both research 
uses and commercial development. For example, our strategy is to 
negotiate non-exclusive licenses whenever possible. This allows more 
than one company to develop products using a particular technology, 
products that may ultimately compete with each other in the 
marketplace. We recognize that companies need an exclusive market to 
offset the risk, time, and expense of developing biomedical diagnostic 
or therapeutic products. However, companies do not necessarily need to 
achieve that position solely by exclusively licensing a government 
technology used to develop the product. Instead, companies are 
frequently able to add their own proprietary technologies to the 
invention licensed from the government to ultimately achieve some level 
of uniqueness and exclusivity for the final product.
    If non-exclusive licensing does not provide enough incentive for 
the company to develop a product, and it often does not for a potential 
therapeutic application, NIH will award exclusivity for specific 
indications or fields of use, based on the license applicant's 
commercial development plans at the time of the application. NIH also 
requires exclusive licensees to grant sublicenses to broaden the 
development possibilities when necessary for the public health. 
Finally, NIH insists on the continuing unencumbered availability of the 
licensed technology to not-for-profit scientific community for further 
research.
    Experience over the last 20 years has shown that to maximize public 
health benefit, the balance between exclusivity and access must be 
carefully maintained and research uses of new technologies must be 
preserved. These concepts form the basis for the licensing policies of 
the NIH, as well as for the proposed guidelines for our grantees 
mentioned above.
Summary
    Congress has enacted legislation for recipients of federal funding 
that encourages the utilization, commercialization and public 
availability of federally funded inventions. Grantees have exercised 
broad discretion and appropriately seek to achieve these goals through 
the patenting and licensing of new inventions that arise through the 
use of federal funds. If the research is entirely funded by the private 
sector, the government has no license and is not involved in patenting 
or licensing decisions. Exclusive licensing, without regard to research 
uses, can impede rather than enhance utilization and public 
availability of certain types of inventions, such as research tools. 
Strategic licensing can alleviate potential problems. Indeed, many 
grantees provide for the continuing availability of exclusively 
licensed subject matter to researchers in order to ensure progress of 
biomedical research. The NIH has urged, and will continue to urge, 
patent owners and exclusive licensees to ensure continuing availability 
under terms that do not limit basic research or encumber future 
products.
    Mr. Chairman, I am grateful to you for providing a forum to present 
information about the effects of patents and licenses on this promising 
new area of science and medicine. I would be pleased to answer any 
questions you may have.

                 summary statement of q. todd dickinson

    Senator Specter. We now turn to Mr. Todd Dickinson, who is 
actually a doctor also, J.D., appears after his name--lawyers 
become doctors--Acting Assistant Secretary of Commerce, Acting 
Commissioner of Patents and Trademarks, B.S., degree in 
chemistry from Allegheny College, law degree from the 
University of Pittsburgh Law School, and he moved from 
northwestern Pennsylvania, to western Pennsylvania, to 
Philadelphia, to practice with the very fine law firm, Deckert, 
Price, & Rose, my old firm.
    Mr. Dickinson, we welcome you here, and look forward to 
your testimony.
    Mr. Dickinson. Thank you, Senator. I want to thank you and 
the committee for providing the opportunity to discuss the 
patent system, more specifically the patenting of biotechnology 
that affects particularly stem cells.
    It is my understanding you have been recently considering 
the scientific implications of this research and are now 
interested in investigating the patent and technology transfer 
implications.
    The history of the U.S. patent system is a long and 
distinguished one. It is grounded in the Constitution. The 
first Patent Act was passed in the 1790's by the first Congress 
sitting in Philadelphia.
    The premise on which the patent system is based is a simple 
one. In exchange for a full and complete disclosure of an 
invention, the Government grants a limited right in the 
invention to an inventor. It is not a monopoly right to own an 
invention as is sometimes suggested, but rather it is the right 
to exclude others from making, using, or selling it, and at the 
patent owner's discretion that right may or may not be 
exercised.
    The public benefits from this arrangement, because full 
disclosure permits others to improve that technology by either 
developing alternative solutions or finding a better alternate 
species invention within the broad genus of the patent claim. 
This expands mankind's technological base.
    Additional benefits include preventing wasteful duplication 
of R&D, a comprehensive teaching of the technology, and an 
indexing of the technology through our patent classification 
system.
    The current patent statute dates from 1952 and specifies 
that to obtain a patent the applicant must meet basic statutory 
requirements: that the claimed invention be statutory subject 
matter; that it be novel, or new, that means it was not 
invented before; that it not be obvious to a person having 
ordinary skill in the art to which it pertains; and that it be 
fully and unambiguously disclosed in the text of the 
application sufficient to enable the skilled practitioner to 
practice it.
    It is also important to remember it is a limited grant in 
time. The patent term runs for 20 years from the date the 
application is filed. After it expires anyone is free to use 
it. This brings me to the specific matter of biotechnology we 
talked about today. Biotechnology generally and broadly 
encompasses any technique that uses living organisms or their 
components to make or modify products, to improve plants or 
animals, or to use microorganisms for specific usage.
    As has been, I think, testified to many times, 
biotechnology has begun to affect our daily lives in ever-
increasing ways. It is opening new pathways in the treatment of 
disease, and showing promising alternatives to less traditional 
methods.
    A serious downside of research and development in 
biotechnology is that it is voraciously expensive, and often 
requires substantial time periods for commercial development. 
Moreover, many lines of research eventually prove to have been 
fruitless, yet the successful results, once known, are often 
not difficult to replicate by others.
    Other factors, including public perception regarding things 
that are new and different, often keep many biotechnology 
inventions from reaching their full market potential. 
Consequently, very few biotechnology companies are profitable 
at this time. Many continue to require substantial additional 
investment to maintain their operations.
    As a consequence, the biotechnology industry has a 
demonstrated need for patent protection to act as an effective 
incentive for innovation and to serve as a tangible asset for 
investment purposes.
    One exciting development in biotechnology research has been 
the isolation and purification of a particular type of 
undifferentiated cells that can give rise to specialized 
functional cells. These are known as stem cells and are 
currently the subject of intensive research. Although most 
cells can only divide a limited number of times, the division 
of stem cells can be unlimited, so they serve as a useful tool. 
In addition, some are known as pluripotent stem cells and can 
be developed into a variety of specialized cells.
    Since stem cells are both living and found in nature, a 
question may be legitimately raised whether they constitute 
patentable subject matter under section 101 of our laws. 
Although the question of the patentability of living organisms 
was answered as long ago as 1873 when Louis Pasteur got a 
patent on a type of yeast, 20 years ago the Supreme Court 
answered that question very firmly in the case of Diamond v. 
Chakrabarty, where they found that genetically engineered 
living bacteria were patentable.
    They cited the congressional reports stating Congress 
intended statutory subject matter to include anything under the 
sun that is made by man. Many commentators feel this was a 
major factor in the growth of the biotechnology research 
industry.
    Second, although stem cells do indeed occur in nature, they 
are always mixed with other cell types and do not occur in 
isolated or purified forms. Purified and isolated cells lines 
as well as methods for their purification and isolation 
represent important technological advances.
    They may also have novel or unexpected properties or uses. 
A long line of case law, therefore, suggests that they may 
indeed result in a patent. In another regard, concerns have 
been raised about licensing of technology in the biotechnology 
area, specifically in the context of availability of research 
tools.
    While the PTO does not normally concern itself with these 
issues, we have some experience in these matters and are asked 
to comment.
    Senator Specter. Mr. Dickinson, will you summarize?

                           prepared statement

    Mr. Dickinson. I will do that.
    Licensing can occur in a variety of ways, royalty-bearing, 
royalty-free, exclusive or nonexclusive. Some have speculated 
that licensing may adversely affect these research tools. It 
has been my experience that the realities of the marketplace 
and the goodwill of researchers very often resolve this problem 
very efficiently.
    Senator Specter. Thank you very much, Mr. Dickinson.
    [The statement follows:]
                Prepared Statement of Q. Todd Dickinson
    Mr. Chairman and Members of the Subcommittee: I am Q. Todd 
Dickinson, Acting Assistant Secretary of Commerce and Acting 
Commissioner of Patents and Trademarks. I want to thank you for 
providing me with this opportunity to discuss the patent system, more 
specifically the patenting of stem cells, and the licensing of 
technology. It is my understanding that you have recently been 
considering the scientific implications of research into these cells 
and are now interested in investigating the patent and technology 
transfer implications.
Background
    The history of the U.S. Patent System is a long and distinguished 
one. Grounded in Article 1, Section 8 of the Constitution, the Patent 
Act of 1790 was one of the first statutes passed by the First Congress 
sitting in Philadelphia. The first patent was granted that same year to 
Samuel Hopkins, also of Philadelphia, for a method of making potash, a 
chemical useful for fertilizer and gunpowder--critical technologies for 
a new, agriculturally based nation. The application was examined by the 
first patent examining board: Secretary of State Thomas Jefferson, 
Attorney General Edmund Randolph and Secretary of War Henry Knox. The 
patent itself was personally signed by the President of the United 
States, George Washington.
    The system has evolved in many ways since that auspicious 
beginning, and continues to serve the primary function it was intended 
to serve by the Founding Fathers: as an incentive to technological 
innovation and economic growth. From the cotton gin to the computer, 
America has been a model for technological development throughout its 
history, and patents have provided protection for the fledgling 
enterprises that were based on that innovation. For example, Thomas 
Edison still holds the record as the individual inventor holding the 
most patents, and his efforts led to the General Electric Co., one of 
the most successful and valuable corporations in the United States.
    The premise on which the system is based is a simple one: in 
exchange for a full and complete disclosure of an invention, the 
government grants a limited right in that invention to the inventor or 
his or her assignee. It is not a monopoly right to own an invention, as 
is sometimes suggested, but rather the right to exclude others from 
making, using, or selling it. Moreover, at the patent owner's 
discretion, this right may or may not be exercised.
    The public benefits from this arrangement since full disclosure 
permits others to improve that technology by developing alternative 
solutions, or to find a better, unexpected species invention within the 
broad genus of the patent claim, thereby expanding mankind's 
technological base. Additional benefits include preventing wasteful 
duplication of research and development; a comprehensive teaching of 
the technology, permitting it to be used efficiently after the patent 
term expires; and the creation of indexed databases of technology in 
the form of the patent classification system which permit easier and 
more comprehensive searching.
    Studies have consistently shown that many important industries rely 
on a strong and effective patent system. University of Pennsylvania 
economist Edwin Mansfield surveyed 100 U.S. corporations chosen 
randomly in six industries. \1\ In each case, he asked senior 
management if strong intellectual property laws were a significant 
consideration for different kinds of investment the corporation would 
make in a particular country. The survey found that approximately 60 
percent of companies investing in final product manufacturing 
facilities said that intellectual property rights had a ``strong 
effect'' on whether direct investment would be made. In chemical, 
pharmaceutical, or electrical equipment manufacturing, the percentages 
were even higher, between 74 and 87 percent. Even more telling, when 
executives were asked if they would invest in research and development 
facilities (the top end of wealth creation in an economy), 80 percent 
said that the strength or weakness of intellectual property rights in a 
country would have a strong effect on whether the company invests 
there.
---------------------------------------------------------------------------
    \1\  E. Mansfield; ``Intellectual Property Protection, Foreign 
Direct Investment and Technology Transfer''; International Finance 
Corporation, Discussion Paper Number 19, The World Bank, 1994.
---------------------------------------------------------------------------
    Non-profit research institutions also benefit financially from 
strong intellectual property protection. The largest public university 
system in the United States is the University of California with over 
7,000 faculty members among its 9 campuses. In 1997, the University had 
2,943 active inventions. Revenues on those patent and technology 
licenses produced $74.7 million for the University in 1997. Carnegie 
Mellon University in Pittsburgh recently assigned a patent claiming 
spidering technology used to search the World Wide Web to Lycos for a 
reported $500,000 in cash, 20 percent equity in the start-up and an 
unspecified percentage of royalties.
    In the biotechnology field, this effect is even more apparent. I 
recently participated in a conference hosted by members of the European 
Parliament who were finally successful in passing a new biotechnology 
patent law for Europe after more than ten years of effort. (It is 
reputed to be the most extended debate ever about a piece of 
legislation before the European Parliament.). Speaker after speaker 
bemoaned the fact that the absence of such legislation in Europe, and 
the presence of strong biotechnological patent protection in the U.S., 
had caused significant research and development funds, manufacturing 
investment, and large numbers of research scientists to relocate to the 
United States.
U.S. Patent Law
    The current patent statute, title 35 of the United States Code, 
dates from 1952, and specifies that to obtain a patent the applicant 
must meet four basic statutory requirements: that the claimed invention 
be statutory subject matter (35 U.S.C. Sec. 101); that it be novel, 
i.e., that it was not invented before (35 U.S.C. Sec. 102); that it not 
be obvious to a person having ordinary skill in the art to which it 
pertains (35 U.S.C. Sec. 103); and that it be fully and unambiguously 
disclosed in the text of the patent itself, sufficient to enable the 
skilled practitioner to practice the claimed invention (35 U.S.C. 
Sec. 112). If the patent application and its claims do not meet these 
requirements, it is rejected. These requirements are not easy hurdles 
to overcome. Section 103 non-obviousness, in particular, requires a 
careful review of the state of the art and often very skillful crafting 
of claims to avoid it. In the biotechnology field, the section 112 
enablement requirement is often a major stumbling block.
    It should also be noted that the claims are the only legally 
operative portion of the patent itself. Readers of patents often 
incorrectly assume that the teaching of the detailed description or 
background of the invention found in the body of the patent in some way 
defines the metes and bounds of the protected invention, or that the 
``concept'' of the invention taught in the claims is what is covered. 
This is incorrect. Furthermore, while the applicant may be his or her 
own lexicographer and define terms, undisclosed meanings not apparent 
in the text cannot be read into a claim and inferences cannot be drawn; 
the plain language of the claim alone defines the parameters of the 
invention. This means that claim interpretation is a difficult and 
often semantic art.
    It is also important to remember that the patent grant is a limited 
right in time. The patent term runs for twenty years from the date that 
the application is filed. After it expires, anyone is free to use it. 
Furthermore, owners of patents do not necessarily have to enforce their 
rights: they can and do dedicate them to the public. Since a patent may 
not be granted on an invention known to the public for more than a 
year, inventors may also dedicate their inventions to the public 
through public disclosure without filing applications
Biotechnology and Stem Cell Research
    Biotechnology generally encompasses any technique that uses living 
organisms or their components to make or modify products, to improve 
plants and animals, or to use microorganisms for specific uses. 
Biotechnology has begun to affect our daily lives in ever-increasing 
ways. It is opening new pathways in the treatment of incurable diseases 
and is showing promising alternatives to less effective traditional 
treatments. In the field of nutrition, biotechnology makes ever-greater 
headway to improve food production and plant breeding in a manner that 
one could only dream about a decade ago. In the field of genetics, the 
use of new techniques is beginning to open substantial and wide-ranging 
benefits for human and animal health, the protection of the environment 
and the potential for productivity gains in food, agricultural and 
pharmaceutical industries.
    A serious downside of research and development in the biotechnology 
area is that it is voraciously expensive and often requires substantial 
time periods for commercial development. Moreover, many lines of 
research eventually prove to have been fruitless. Yet, the successful 
results, once known, are often not difficult to replicate by others. 
Other factors, including public perception regarding anything new and 
different, also keep many biotechnology inventions from reaching their 
full market potential. Consequently, very few biotechnology companies 
are profitable at this time. Many continue to require substantial 
additional investment to maintain operations. As a consequence, the 
biotechnology industry has a demonstrated need for patent protection to 
act as an effective incentive to innovation and to serve as a tangible 
asset for investment.
    One exciting development in biotechnology research has been the 
isolation and purification of particular types of undifferentiated 
cells that can give rise to a succession of specialized functional 
cells. These are known as stem cells, and are currently the subject of 
intensive research. Although most non-cancerous cells can divide only a 
limited number of times, the division of stem cells can be unlimited 
and may serve as a useful tool in solving many previously intractable 
medical conditions. In addition some stem cells are ``pluripotent'' 
cell lines, meaning they can be made to develop into a variety of 
different specialized cells.
Patentability
    Since stem cells are both living and found in nature, however, a 
question that may legitimately be raised is how they can constitute 
patentable subject matter under Sec. 101 of our patent law. Although 
the question of the subject matter patentability of living organisms 
may have been answered as long ago as 1873, when Louis Pasteur was 
granted a United States patent on yeast, it was most firmly addressed 
by the Supreme Court almost twenty years ago in the famous case Diamond 
v. Chakrabarty \2\. In that case, Chief Justice Burger, writing for the 
Court, found that genetically engineered bacteria useful for cleaning 
up oil spills by ingesting hydrocarbons were themselves patentable. As 
noted by the Court (citing the Congressional Report accompanying the 
1952 Act \3\), ``Congress intended statutory subject matter to include 
anything under the sun that is made by man''. Many commentators believe 
that this case was a major factor in the phenomenal growth of the 
biotechnology industry. And it should also be noted that the PTO has 
long issued patents to living plants under the provisions of the Plant 
Patent Act of 1930.
---------------------------------------------------------------------------
    \2\ 447 U.S. 303, 65 L.Ed.2d 144, 100 S.Ct. 2207, 206 U.S.P.Q. 193 
(1980).
    \3\ S. Rep. No. 1979, 82nd Cong., 2d Sess., 5 (1952); H.R. Rep. No. 
1923, 82nd Cong., 2d Sess., 6 (1952).
---------------------------------------------------------------------------
    Moreover, although stem cells do indeed occur in nature, most 
evidence indicates that they are always mixed with other cell types and 
do not occur in an isolated and purified form. Purified and isolated 
cell lines, as well as methods for their purification and isolation, 
represent important technological advances. They may also have novel or 
unexpected properties or uses, and may therefore result in a patent. 
\4\ As stated by the Supreme Court, ``To obtain a patent for a product 
made from raw material, it must possess a new or distinctive form, 
quality, or property.''\5\
---------------------------------------------------------------------------
    \4\ See generally Bozicevic, ``Distinguishing `Products of Nature' 
from Products Derived from Nature,'' 69 Journal of the Patent and 
Trademark Office Society 415 (1987).
    \5\ American Fruit Growers, Inc. v. Brodex Co., 283 U.S. 1, 11, 8 
U.S.P.Q. 131, 133 (1931).
---------------------------------------------------------------------------
    The patentability of biologically pure compositions has been the 
law for over twenty years. In In re Bergy (1977) \6\, the Court of 
Customs and Patent Appeals (the predecessor court to the Court of 
Appeals for the Federal Circuit (CAFC), the appeals court to which PTO 
appeals are taken) ruled that a biologically pure bacterial culture was 
patentable, and not a ``product of nature'', since the culture did not 
exist in nature in its pure form and could only be produced in a 
laboratory under carefully controlled circumstances. \7\ This has been 
extended since that time to ```purified and isolated' DNA sequences 
encoding human erythropoietin (EPO)'', \8\ and a preparation of Factor 
VIII: C, used for treating hemophilia. (``Although Factor VIII: C 
molecules occur in nature, a purified and concentrated preparation of 
Factor VIII: C as claimed in the patent constitutes a new form or 
combination not existing in nature, and hence is patentable under 35 
U.S.C. Sec. 101.'') \9\
---------------------------------------------------------------------------
    \6\ 568 F.2d 1031, 195 U.S.P.Q. 344 (ccpa 1977).
    \7\ The Supreme Court granted certiorari, but summarily remanded to 
the CCPA in light of another related case. The CCPA later affirmed its 
earlier opinion.
    \8\ Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 13 USPQ2d 1737, 
aff'd in part, rev'd in part, vacated in part, 927 F.2d1200, 18 USPQ2d 
1016 (Fed Cir. 1991), cert. denied, 112 S. Ct. 169 (1991).
    \9\ Scripps Clinic & Research Foundation v. Genentech Inc., 666 
F.Supp. 1379, 1389 n.6, 3 USPQ2d 1481, 1487 n6. (N.D. Calif. 1897), 
aff'd.in part, rev'd in part, vacated in part and remanded, 927 F.2d 
1565, 18 USPQ2d 1001.
---------------------------------------------------------------------------
    Accordingly, it is the present position of the Patent and Trademark 
Office that purified and isolated stem cell lines are patentable 
subject matter under 35 U.S.C. Sec. 101.
Licensing
    Concerns have also been raised regarding the licensing of 
technology in the biotechnology area, specifically in the context of 
the availability of research tools. While the Patent and Trademark 
Office does not normally concern itself with access issues, we do have 
responsibility for intellectual property policy generally, and, as 
such, have some experience in these matters.
    A traditional way to exploit one's patent is to license it to 
others, under a wide variety of possible terms: exclusive or non-
exclusive; royalty-free or royalty bearing. Patent owners may also 
choose not to license, for a variety of reasons, such as a desire to 
preserve exclusivity or maintain competitive advantage. This right is 
fundamental to the patent grant.
    While some speculate that patent owners who refuse to license or 
exclusively license others may adversely affect access to 
biotechnological research tools, it has been my experience that market 
realities and/or good will almost always resolve this problem. One 
famous example may prove illustrative.
    Almost two decades ago, Stanford University was granted a patent on 
a method covering basic recombinant DNA technology, the so-called 
Cohen-Boyer patent, U.S. Patent Number 4,237,224. Because of the 
fundamental nature of the technology, great public concern was raised 
that biotechnology research would be blocked, or that Stanford would 
charge such exorbitant royalty rates that research would be priced out 
of reach. In reality, nothing of the sort occurred. Stanford quickly 
developed a reasonable and widely available licensing program and 
alternative technologies were developed to compete with it. Because the 
licenses were offered at reasonable rates to all who sought them, 
technology was not stymied. Improvements to the technology also arose 
resulting in a moderating cross-licensing program.
    Another question which has been raised concerns specific additional 
grants or limitations contained in certain licensing agreements. These 
include such provisions as a requirement that any improvements in the 
licensed technology be licensed back to the patent holder, commonly 
known as grant-backs. Provisions such as this are fairly common in 
commercial technology licenses, although they are also often the 
subjects of significant negotiation.
    It is also important to note that many of these aspects of 
intellectual property licenses may be subject to antitrust scrutiny. 
See, for example, the Antitrust Guidelines for the Licensing of 
Intellectual Property, recently promulgated by the Antitrust Division 
of the Justice Department and the Federal Trade Commission.
    In the context of these licensing considerations, it is also 
important to define specifically what ``research tools'' are being 
implicated in these concerns. Many of the instruments, chemicals and 
equipment used daily in research have patented technologies associated 
with them. A license to practice under those patents, and the related 
royalties, are often captured in the purchase price.
    Last, and significantly, it should be noted that restrictions on 
licensing or subject matter patentability must also comply with United 
States international obligations. Through protracted negotiations, the 
U.S. has convinced many of our trading partners of the great value of 
intellectual property protection and has been able to reach agreement 
with them to provide strong intellectual property protection. In fact, 
we were able to incorporate our position on intellectual property 
protection into the Uruguay Round Trade Agreements of GATT. The 
Agreement on Trade-Related Aspects of Intellectual Property Rights 
(TRIPS) requires the United States and all other members of the World 
Trade Organization to provide similar patent protection for all 
patentable subject matter.
    We have encouraged strong pharmaceutical patent protection by our 
trading partners and must continue to provide strong patent protection 
for biotechnological inventions, such as cell lines. That protection 
should not be diminished by inappropriate incursions into the rights of 
the patent owner. In fact, U.S. patent policy toward our trading 
partners strongly discourages compulsory licenses or any other such 
limitations on a patent holder's rights.
    While we certainly share concerns about access to technology, and 
would highly recommend that oversight of potential abuses be 
maintained, the balance of interests in this area is currently a 
carefully calibrated one, and should not be upset absent strongly 
reasoned analysis and demonstration of actual harm.
Summary
    The United States leads the world in biotechnology research and 
development. We also lead the world in intellectual property 
protection. It is imperative to the former that we maintain the latter. 
As stated long ago by President Abraham Lincoln, a patent holder 
himself: the patent system has ``added the fuel of interest to the fire 
of genius.'' Our continued success as the most technologically advanced 
nation in the history of the world demands that we honor that system 
and the benefits it brings.
    Thank you.

                     remarks of senator tom harkin

    Senator Specter. Let me turn, before we go to a round of 
questioning, to my distinguished colleague, the ranking member, 
Senator Harkin.
    Senator Harkin. Thank you very much, Mr. Chairman. I 
apologize for being a little bit late, and I thank you for 
convening this very important hearing. I just had a couple of 
statements, if I might make them here.
    This really is going to help us get a much better 
understanding of the patenting and licensing issues, 
particularly as they apply to the recent discovery of human 
embryonic stem cells.
    Last month we heard the Department of Health and Human 
Services General Counsel's Office was examining whether the 
current ban on human embryo research, whether NIH-funded 
scientists could conduct research on the stem cells lines 
isolated by Dr. Thompson and Dr. Gearhart.
    As I recall, at our last hearing, every scientist present 
stated their belief that the stem cells are not organisms and, 
therefore, cannot fall under the Federal ban.
    Shortly after the hearing last month, I sent a letter to 
Secretary Shalala requesting her timely decision on this issue, 
and I must say I am very disappointed that this has not yet 
been done and the decision has not yet been made by HHS. It 
seems obvious to me and every scientist who testified here last 
month that this research can be federally funded.
    Now, with or without Federal funding, some of the research 
community have questioned the availability of these cells 
lines, questioning whether or not they can be available to 
nonprofit scientists. They believe the content of the licensing 
agreements and what some perceive to be overly broad patent 
claims can hinder others from using these cells lines.
    Now, again, I do not pretend to know the answer to these 
questions. I am pleased that we have the people here today to 
testify on this.
    I must say that I am disappointed that we did not have here 
today witnesses from one or more of the private companies 
involved in this to hear their side of the story, although I do 
understand, Mr. Chairman, that--at least my staff tells me that 
they are going to submit a statement for the record. Can you 
enlighten me on that?
    Senator Specter. Well, it is pretty hard just to have a 
statement for the record. It is pretty hard to have a hearing 
without witnesses.
    Senator Harkin. Well, I agree with you. I wish they had 
shown up. I would like to have questioned them.
    Senator Specter. Or a trial without witnesses.
    Senator Harkin. Well, it depends on what kind of trial you 
are talking about. [Laughter.]
    Are you talking about a courtroom trial?
    Senator Specter. We can agree on a hearing with witnesses. 
[Laughter.]
    Senator Harkin. We can agree on a hearing with witnesses. 
[Laughter.]
    Senator Specter. Senator Harkin, they have submitted a 
draft statement, but I commented before you arrived that I was 
a little disappointed that Geron did not appear.
    Senator Harkin. Well, I am, too.
    Senator Specter. Because, without mentioning impeachment, 
we really need to be able to ask them questions and have a 
dialog, and their absence here does not help the subcommittee 
on moving ahead with its conclusions. We have a draft 
statement, and perhaps we can hear them at a later time. I 
think the parties are even subject to subpoena under a variety 
of rules in our Senate.
    Senator Harkin. Well, I am sorry, Mr. Chairman. I do not 
know what you want to do with that statement, whether you want 
to make it a part of the record. That is fine with me.
    Senator Specter. We will make it a part of the record for 
whatever value it has, but I concur with you that we need them 
here to respond to questions.
    Senator Harkin. Well, I agree. I am glad we agree on that, 
Mr. Chairman, but at least we have the people who are here 
today and some other scientists to talk about applications of 
this in terms of health care. My interest in this hearing today 
was to get a better understanding of the Bayh-Dole Act, the 
Stevenson-Wydler Act, and how these apply in genetics and in 
the stem cell areas particularly, and what that means in terms 
of licensing arrangements under the patents that they hold.
    I remember in 1980, when Bayh-Dole was passed, I was in the 
House and I was chairing the subcommittee that had jurisdiction 
over the National Science Foundation, and I remember at that 
time the problems that we had with private entities coming in, 
putting the money into research, and not being assured that 
they could have a patent or something for future recompense for 
the money that they had invested. That was a big stumbling 
block.
    I remember an invention that had been developed at Iowa 
State University. I am searching my memory for exactly what it 
was, but because of the inability to obtain a patent on it, a 
Japanese company had come in and taken it and was manufacturing 
it and selling it in this country.

                           prepared statement

    So that propelled us in 1980 to pass this bill to try to 
strike a balance between the public interest and the need to 
raise the private moneys to engage in this kind of expensive 
research so that people could be guaranteed they would get some 
return on that investment and to bring these products to 
market, to get them out of the lab and get them to market.
    Our first witness said something about a dilemma. I will 
not go into that. I will just ask that the rest of my statement 
be made a part of the record.
    [The statement follows:]
                Prepared Statement of Senator Tom Harkin
    Thank you, Chairman Specter, for convening this important hearing. 
I had requested this hearing in order to get a better understanding of 
patenting and licensing issues, particularly as they apply to the 
recent discovery of human embryonic stem (hES) cells.
    Last month, we heard that the Department of Health and Human 
Services' General Counsel's office was examining whether, under the 
current ban on human embryo research, NIH-funded scientists could 
conduct research on the hES cell lines isolated by Dr. Thomson at the 
University of Wisconsin and Dr. Gearhart of Johns Hopkins. As I recall, 
at our last hearing every scientist present stated their belief that 
hES cells are not organisms, and therefore cannot fall under the 
federal ban. Shortly after the hearing last month, I sent a letter to 
Secretary Shalala requesting her timely decision on this issue, and I 
must say I am very disappointed that she has not yet been able to make 
a decision on this. It seems obvious to me--and to every scientist who 
testified here last month--that this research can be federally-funded.
    But with or without federal funding, there are some in the research 
community who question the availability of these cell lines to non-
profit scientists. They believe that the content of the licensing 
agreements, and what some perceive to be overly broad patent claims, 
could hinder others from using these cell lines. I don't pretend to 
know the answer to these questions, so I am very pleased that we have 
an opportunity to hear from patent and technology transfer experts 
Maria Freire from the NIH and Todd Dickinson from the Patent and 
Trademark Office (PTO), to get their views on the matter.
    I am also glad to hear today from cell biologist Dr. Lawrence 
Goldstein, Mr. Richard Pikunis, who suffers from Parkinson's disease, 
and Dr. Douglas Melton on behalf of the Juvenile Diabetes Association. 
We learned a great deal from the hearing last month about the 
technology and methods for isolating hES cells, now is our chance to 
learn from the second panel about the hope this new technology offers 
to the millions of Americans who suffer from these diseases, and the 
critical need for federal funding of this research.
    The ground breaking research done by Dr. Thomson and Dr. Gearhart 
shows tremendous promise. From enabling the development of cell and 
tissue transplantation, to improving and accelerating pharmaceutical 
research and development, to increasing our understanding of human 
development and cancer biology, the potential benefits of their work 
are truly awe-inspiring.
    Therefore, my primary goal for this hearing is to make sure 
Congress is doing what it can to ensure that research moves forward, 
without unreasonable impediments or delays. However, I want to make it 
clear that I do not believe that research should be done solely for 
research's sake. We must continue to ensure that incentives are in 
place for promising inventions to get to market. That is why we have 
invested all we have in biomedical research--so that these inventions 
can be used to cure and treat the diseases affecting the American 
people. To this end, I believe the patent system and the Bayh-Dole law 
have been very successful.
    However, as I stated earlier, some in the research community have 
raised concerns about their access to ``research tools,'' which I 
understand include these new stem cell lines. They say that dealing 
with the required bureaucratic paperwork slows down their research, and 
that the cost of access to these tools increases the overall cost of 
research, which leads to higher and higher costs of the product for the 
eventual consumer.
    Others in the research community maintain that the system works 
well and should not be changed. They say that without intellectual 
property rights, the biotechnology industry would have little incentive 
to invest in the time-consuming and expensive research and development 
(R&D) required to bring a product to market.
    I believe it would be a travesty if the potential benefits of stem 
cell research--or any research for that matter--are delayed or denied 
to patients for any reason: Whether it is because the add-on cost of 
access to research tools is too expensive, or because companies lack an 
incentive to bring a product to market. It is therefore critical that 
we maintain a healthy balance of incentives between the federal 
government, non-profit research institutions and the private sector.
    I hope today's hearing will help clarify this debate.

                            Time constraints

    Senator Specter. In light of our time constraints, I said 
to Senator Harkin before you arrived that Senator Lott had 
scheduled the session on the impeachment issue at 10 o'clock, 
which is why we had moved the hearing to 9 o'clock.
    Senator Harkin. We are in session at 10 o'clock?
    Senator Specter. No; it is not in session, it is a meeting 
among Republican Senators.
    Senator Harkin. An open meeting? [Laughter.]
    Senator Specter. I think only the closing statements are 
open, Senator Harkin. [Laughter.]
    If you missed Senator Harkin on C-SPAN last night, he was 
not quite as erudite as this morning, but very erudite. 
[Laughter.]
    In the interests of time we are going to call the next 
panel, and if you would stay where you are, and then we will 
move to questions among all five of the witnesses.
                       NONDEPARTMENTAL WITNESSES

STATEMENT OF LAWRENCE GOLDSTEIN, Ph.D., PROFESSOR OF 
            PHARMACOLOGY, DIVISION OF CELLULAR AND 
            MOLECULAR MEDICINE, UNIVERSITY OF 
            CALIFORNIA AT SAN DIEGO

                           summary statement

    Senator Specter. Our first witness on the second panel is 
Dr. Lawrence Goldstein, professor of pharmacology at the 
Division of Cellular and Molecular Medicine, University of 
California. He serves as an investigator for Howard Hughes 
Medical Institute at the University of California at San Diego, 
Ph.D., from the University of Washington. Welcome, Dr. 
Goldstein, and the floor is yours for the next 5 minutes.
    Dr. Goldstein. Thank you, Senator.
    Mr. Chairman and members of the subcommittee, I am Lawrence 
Goldstein and I am here today as a representative of the 
American Society for Cell Biology. The society represents over 
9,000 biomedical researchers throughout the United States and 
the world, most of whom work in our Nation's leading research 
universities and institutes.
    As you said, my own research is conducted in the Division 
of Cellular and Molecular Medicine at the University of 
California San Diego School of Medicine.
    Before moving to San Diego, I was on the faculty in the 
Department of Cellular and Developmental Biology at Harvard 
University for 10 years. My research work concerns molecular 
and genetic analysis of protein motors and their roles in 
cellular growth, function, and development.
    I speak today on the need to ensure life-saving progress in 
medical research while simultaneously protecting ethical and 
moral decency. As you know, scientific advances are emerging at 
a blinding pace. These advances present Congress with a serious 
challenge. You must find a balance between on the one hand 
assuring the public that new knowledge will not be misused and 
that the ethics of such work will be carefully considered, 
while on the other hand ensuring that critical medical research 
is not impeded because of unnecessary fear or insufficient 
information.
    The specific issue today concerns human stem cells, which 
have extraordinary potential to revolutionize the treatment and 
cure of devastating human diseases. Already, in the short time 
since the generation of these cells was announced, we can 
conceive of many important applications in the treatment of 
heart disease, diabetes, Parkinson's disease, and Alzheimer's 
disease. In fact, the list of possible therapeutic uses is 
almost endless.
    These broad applications are likely, because it may be 
possible to coax stem cells to become the many types of cells 
often lost to the ravages of disease.
    My colleague, Nobel Laureate Dr. Paul Berg of Stanford 
University, stated in a recent letter to you that currently 
only scientists who receive private, non-Federal funding may 
pursue stem cell research. This has the effect of excluding the 
majority of the Nation's most prominent researchers, who are 
supported by the NIH and NSF, and are based at universities and 
nonprofit institutions throughout the country.
    The current exclusion limits the development of new 
therapies, and relies exclusively on the commercial sector to 
reap the benefits of scientific insights originally developed 
with the generous support of the Federal Government.
    Recent work with stem cells from fetal tissue is 
permissible under current Federal guidelines. However, we first 
seek to persuade this committee and the Congress to make the 
informed and courageous decision to ensure that those 
scientists who are most prepared and best-qualified to conduct 
safe, ethical, and invaluable embryonic stem cell research be 
allowed to do so.
    Allowing peer-reviewed Federal funds to be used for this 
type of research is our best guarantee the quality of the work 
will be high, and the results can be best used to serve the 
public good.
    Senator Harkin went to great lengths at your last hearing 
to point out that the current ban on embryo research does not 
expressly prohibit federally funded scientists from conducting 
the research using human embryonic stem cells. We agree with 
the Senator's understanding, and await the Department of Health 
and Human Services' interpretation of the current law.
    In any discussion of this issue, however, it is essential 
to define clearly and to distinguish among varying types of 
human stem cells, and there are at least two kinds.
    First are totipotent stem cells, which have the theoretical 
and perhaps real potential to become any kind of cell and could 
perhaps, under appropriate conditions, such as implantation in 
a uterus, become an entire individual.
    Second are pluripotent stem cells, such as those that can 
be obtained from an early stage embryo, which have a more 
limited potential in that they can only form certain kinds of 
cells such as muscle, nerve, or blood. Thus, pluripotent stem 
cells that are derived from the inner cell mass of a blastocyst 
are not capable on their own of embryological development, or 
the creation of a human being.
    It may, though, be possible to induce these cells to form 
certain specialized cell types that make up important human 
tissues such as those of the liver, pancreas, skin, heart, and 
nerves, and it is this potential which makes these stem cells 
such an important resource to develop for therapeutic uses.
    To this end, the society supports the elimination of the 
existing prohibition of Federal funding for research with human 
embryos and specialized cells derived from them. Research with 
human embryos obtained by ethically validated means and 
specialized cells derived from them should be allowed to 
proceed in a way that would assure the public that the cloning 
of a human being is prohibited, and that ethical considerations 
are guaranteed.
    In closing, the society enthusiastically supports your 
efforts to highlight for the public and your colleagues in the 
Senate the potential value of modern scientific techniques for 
improving human health.

                           prepared statement

    Stem cell research in particular has enormous potential for 
the effective treatment of human disease. Thus, we believe 
there is a moral imperative to do it in an ethically validated 
manner. We must not close off scientific opportunity to those 
most qualified to make dramatic strides in the cure of disease 
through the use of stem cells.
    Mr. Chairman, thank you for the opportunity to present my 
thoughts today.
    Senator Specter. Thank you very much, Dr. Goldstein.
    [The statement follows:]
         Prepared Statement of Lawrence S. B. Goldstein, Ph.D.
    Mr. Chairman and members of the Subcommittee: I am Lawrence 
Goldstein. I am here today as a representative of the American Society 
for Cell Biology. The Society represents over 9,000 basic biomedical 
researchers throughout the United States and the world, most of whom 
work in our Nation's leading research universities and institutes.
    My own research is conducted in the Division of Cellular and 
Molecular Medicine and the Department of Pharmacology at the University 
of California, San Diego School of Medicine. I am also an Investigator 
of the Howard Hughes Medical Institute. Before moving to San Diego I 
was on the faculty in the Department of Cellular and Developmental 
Biology at Harvard University for 10 years. My research work concerns 
molecular and genetic analysis of protein motors and their roles in 
cellular proliferation, function, and development.
    I speak today on the need to ensure life-saving progress in medical 
research, while simultaneously protecting ethical and moral decency. As 
you know, scientific advances are emerging at a blinding pace. These 
advances present Congress with a serious challenge. You must find a 
balance between assuring the public that new knowledge will not be 
misused and that the ethics of such work will be carefully considered, 
while ensuring that critical medical research is not impeded because of 
unnecessary fear or insufficient information.
    The specific issue today concerns human stem cells, which have 
extraordinary potential to revolutionize the treatment and cure of 
devastating human diseases. Already, in the short time since the 
generation of these cells was announced, we can conceive of many 
important applications in the treatment of heart disease, diabetes, 
Parkinson's disease, Alzheimer disease, spinal cord injury; in fact, 
the list of possible therapeutic uses is almost endless. These broad 
applications are possible because it may be possible to coax stem cells 
to differentiate into the many types of cells often lost to the ravages 
of disease.
    My colleague, Nobel Laureate Dr. Paul Berg of Stanford, stated in a 
recent letter to you that:
    Currently, only scientists who receive private (non-federal) 
funding may pursue [stem cell] research. This has the effect of 
excluding the majority of the Nation's most prominent researchers who 
are supported by the NIH and NSF and are based at universities and non-
profit institutions throughout the country. The current exclusion 
limits the development of new therapies and relies exclusively on the 
commercial sector to reap the benefits of scientific insights developed 
with the generous support of the federal government.
    Recent work with stem cell from fetal tissue is permissible under 
current federal guidelines. We further seek to persuade this Committee 
and the Congress to make the informed and courageous decision to ensure 
that those scientists who are most prepared and qualified to conduct 
safe, ethical and invaluable stem cell research be enabled to do so. 
Allowing peer-reviewed federal funds to be used for this type of 
research is our best guarantee that the quality of the work will be 
high and that the results can be best used to serve the public good.
    Senator Harkin went to great lengths at your last hearing to point 
out that the current ban on embryo research does not expressly prohibit 
federally-funded scientists from conducting research using human stem 
cells. We agree with the Senator's understanding and await the 
Department of Health & Human Services' interpretation of the current 
law.
    In any discussion of this issue, it is essential to define clearly 
and to distinguish among various types of human stem cells. There are 
at least two kinds of stem cells:
  --Totipotent stem cells have the theoretical, and perhaps real, 
        potential to become any kind of cell, and under appropriate 
        conditions, such as implantation in a uterus, could become an 
        entire individual.
  --Pluripotent stem cells, such as those that can be obtained from an 
        early stage embryo, have a more limited potential, including 
        those which are more committed, in that they can form only 
        certain kinds of cells, such as muscle, nerve or blood cells, 
        but they cannot form a whole organism.
    Pluripotent stem cells that are derived from the inner cell mass of 
a blastocyst are not capable on their own, however, of embryological 
development or the creation of a human being. It may, though, be 
possible to induce these cells to form certain specialized cell types 
that make up important human tissue, such as those of the liver, 
pancreas, skin, heart, and nerves. It is this potential which makes 
stem cells such an important resource to develop for therapeutic uses.
    To this end, the Society supports the elimination of the existing 
prohibition on federal funding for research with human embryos and 
specialized cells derived from them. Research with human embryos 
obtained by ethically validated means, and specialized cells derived 
from them, should be allowed to proceed in a way that would assure the 
public that the cloning of a human being is prohibited, and that 
ethical considerations are guaranteed.
    The Society enthusiastically supports your efforts to highlight for 
the public and your colleagues in the Senate the potential value of 
modern scientific techniques for improving human health. Stem cell 
research, in particular, has enormous potential for the effective 
treatment of human disease. Thus we believe that there is a moral 
imperative to pursue it in an ethically validated manner. We must not 
close off scientific opportunity to those most qualified to make 
dramatic strides in the cure of disease through the use of stem cells.
    Mr. Chairman, thank you for the opportunity to present my thoughts 
today. I would be pleased to answer any questions.
STATEMENT OF DOUG MELTON, Ph.D., REPRESENTING THE 
            JUVENILE DIABETES ASSOCIATION, HARVARD 
            UNIVERSITY
    Senator Specter. We now turn to Dr. Douglas Melton, 
chairman of the Department of Molecular and Cellular Biology at 
Harvard University, who also serves as an investigator for the 
Howard Hughes Medical Institute, and associate member of the 
Children's Hospital in Boston. Dr. Melton is here today on 
behalf of the Juvenile Diabetes Association and has an extra 
special interest in the issue, since his 7-year-old son was 
diagnosed with the disease at the age of 6 months.
    Welcome, Dr. Melton. The floor is yours.
    Dr. Melton. Good morning, Chairman Specter and Senator 
Harkin. As you noted, I am the chairman of the Molecular 
Biology Department at Harvard, but I am here today both as a 
researcher and a father of a 7-year-old type I diabetic. I am 
here because I feel I can speak to you both about the human 
burden of diabetes and the scientific potential of stem cell 
research.
    Mr. Chairman, before I begin my remarks on the subject of 
today's hearing I want to take this opportunity to thank you 
and other members of the subcommittee for your role, your 
leading role in last year's historic increase in HIH funding. 
The strong bipartisan support for that increase gives renewed 
hope to those of us who are struggling with chronic diseases on 
a daily basis.
    Founded nearly 30 years ago by parents of children with 
diabetes, the JDF is a voluntary health organization that is 
dedicated to finding a cure for diabetes through research and, 
in fact, this year the foundation expects to commit nearly $65 
million directly toward diabetes research.
    Diabetes, as you know, is an insidious disease, and remains 
widely misunderstood by the public, because many people wrongly 
think that insulin is a cure when it is, in fact, merely life 
support.
    Diabetes is the leading cause of new adult blindness, 
kidney disease, and nontraumatic amputations, and it costs this 
country nearly $100 billion a year. That is billion, not 
million; 60 million Americans suffer from diabetes and, on 
average, a person with the disease can expect to live 15 fewer 
years than those without it.
    In addition, and particularly poignant to me, is that it is 
among the most chronic diseases affecting children, and this is 
a group upon which its effects are especially devastating.
    Before I discuss the exciting potential of stem cell 
research, allow me to speak briefly to you as a parent. The 
daily regimen of my son Sam's blood checks and insulin 
injections, up to five of them a day, are coupled with our need 
to balance his diet and exercise. This is, as you might expect, 
a serious challenge in dealing with a 7-year-old soccer player.
    The medical troubles for Sam are compounded by the 
vigilance and worry that extracts a heavy toll on the rest of 
my family. For example, my wife is regularly up late in the 
night doing blood checks while Sam sleeps and we wonder, is his 
blood sugar too low, will he go into a coma during the night.
    I am sorry to say that I cannot recall a night of peaceful 
sleep since Sam was diagnosed nearly 7 years ago, and I am 
unwilling to accept the enormity of the medical and 
psychological burden, and am personally devoted to bringing it 
to an end for my son Sam and for all type I diabetics. I 
implore you to continue to make it possible to cure diabetes 
for diabetics and their families.
    Let me now turn to the main subject of today's hearing. 
That is, the potential cure for diabetes as it relates to human 
stem cell research. As Dr. Goldstein mentioned, based on recent 
discoveries it is now foreseeable that human stem cells could 
be stimulated to develop into a number of cell types, notably 
pancreatic islets. These are the cells that are destroyed in a 
type I diabetic.
    These stem cells then have the potential to develop into 
any tissue organ in the body, and they could no doubt be 
directed to make pancreatic islet or beta cells.
    One of the most promising ways of curing diabetes is to 
restore biologically the function of the missing islet cells, 
and this could occur through islet transplantation, or through 
engineering cells such as these human stem cells.
    The availability of human stem cells which could be turned 
into beta cells would solve two important problems, No. 1, that 
of insufficient islet supply, which presently plagues the field 
and, No. 2, the recurrence of the autoimmune response.
    My written testimony details how it solves the autoimmune 
problem, but let me just say that by engineering stem cells it 
would be possible to avoid the requirement for the 
immunosuppressive drugs.
    I would like to conclude by noting the important ethical 
considerations which your subcommittee has, of course, 
considered. The JDF and I well understand that stem cell 
research has important ethical considerations that need to be 
addressed. However, we feel that appropriate safeguards can and 
should be established to ensure that this important research 
can be conducted using Federal funding.
    The 1994 Human Embryo Research Panel, which included both 
scientists and ethicists, studied the ethical issues raised by 
this type of research, and it is important to note that they 
concluded that stem cell research involving preimplantation 
human embryos is acceptable for Federal funding.
    We believe that that panel's report provides a scientific 
and ethical basis to justify Federal funding for stem cell 
research on human material, and this report could also serve as 
the basis for the establishment of a set of safeguards that 
would ensure that this research was conducted ethically in both 
public and private settings while still allowing for 
significant advances in the fight to cure diabetes.

                           prepared statement

    I will conclude, Mr. Chairman, by thanking you for the 
opportunity to speak today and saying that the opportunities 
presented by human stem cell research offer us the promise of 
truly significant advances and perhaps a cure for diabetes. A 
world without diabetes for all the children and adults who 
suffer from the devastating impact of this disease is the goal 
of the JDF, and we urge you to ensure that Federal policies 
allow this research to continue to speed our path to cure this 
disease.
    Thank you.
    Senator Specter. Thank you, Dr. Melton.
    [The statement follows:]
                Prepared Statement of Doug Melton, Ph.D.
    Good morning Chairman Specter, Senator Harkin and other members of 
the subcommittee. My name is Doug Melton and I appear before you today 
on behalf of the Juvenile Diabetes Foundation International and the 
millions of families in this country touched by diabetes. I am Chairman 
of the Department of Molecular and Cellular Biology at Harvard 
University, but more importantly for today's discussion, I am here 
today because my 7-year-old son, Sam, has had Type 1 (or insulin-
dependent) diabetes since he was 6 months old. I am here this morning 
as a father and a researcher, as someone who can speak to you about the 
human burden of diabetes and the scientific potential of stem cell 
research.
    Mr. Chairman, before I begin my remarks on the topic of this 
morning's hearing, I want to take this opportunity to thank you and the 
other members of this subcommittee for your leading role in last year's 
historic increase in NIH funding. The strong bipartisan support for NIH 
exhibited last year provides renewed hope for those of us struggling 
with chronic disease on a daily basis.
    Founded nearly 30 years ago by parents of children with diabetes, 
JDF is a voluntary health agency dedicated to finding a cure for 
diabetes through the support of research. JDF gives more money to 
diabetes research than any other nonprofit, non-governmental 
organization in the world. This year, the Foundation expects to commit 
nearly $65 million directly to diabetes research.
    Diabetes is an insidious disease, and remains widely misunderstood 
by the general public. Insulin is not a cure for diabetes, it is merely 
life support. Diabetes is the leading cause of new adult blindness, 
kidney disease, and non-traumatic amputations, costing this country 
nearly $100 billion annually. Sixteen million Americans suffer from 
diabetes. On average, a person with diabetes can expect to live 15 
fewer years than someone who does not have the disease. In addition, it 
is one of the most common chronic diseases affecting children, a group 
upon which it has an especially devastating impact.
    Before discussing the exciting potential of stem cell research, 
allow me to speak briefly as a parent. The daily regimen of Sam's blood 
checks and insulin injections (up to 5 per day) are coupled with our 
need to balancing his diet and exercise: a serious challenge in dealing 
with a 7-year-old soccer player. The medical troubles for Sam are 
compounded by the vigilance and worry that extract a heavy toll on the 
rest of the family. For example, my wife is regularly up in the late 
hours of the night doing blood checks while Sam sleeps: we wonder is 
his blood sugar too low? Will he find the middle ground between a 
``low'' or coma and being too ``high'' in the morning? I can't recall a 
night since Sam was diagnosed when we slept peacefully, free of the 
worry that the balance between his food, insulin and exercise was not 
good enough. I'm unwilling to accept the enormity of this medical and 
psychological burden and I am personally devoted to bringing it to an 
end for Sam and all type I diabetics. I implore you to continue to make 
it possible to cure diabetes, for diabetics and their families.
Human Stem Cell Research: A Potential Cure for Diabetes
    I would like to commend the Subcommittee for holding these 
important hearings on stem cell research. The recent discoveries in the 
field hold the potential to end all of this and finally find a cure for 
diabetes.
    Based on these discoveries, it is now foreseeable that human stem 
cells could be stimulated to develop into pancreatic islet cells to 
replace those that have been destroyed in individuals with Type 1 
diabetes. Stem cells have the potential to develop into any tissue or 
organ in the body and yet cannot develop into a full human being. 
Moreover, these cells could be engineered in such a way that people who 
receive them might not need highly toxic immunosuppressive drugs, which 
prevent the body from rejecting ``foreign'' tissue--currently a major 
obstacle to successful islet transplantation.
    One of the most promising ways of curing diabetes is to restore 
biologically the function of islet cells. This could occur either 
through islet cell transplantation or through engineering of cells to 
restore the insulin-secreting function. In both instances, the 
availability of stem cells would significantly expedite research 
progress.
    Islet cell transplantation has been largely unsuccessful for two 
important reasons:
  --Insufficient islets available for transplantation; and
  --Recurrence of the autoimmune response that attacks the islets after 
        transplantation.
    The problem of insufficient supply of islet cells could potentially 
be solved through additional stem cell research. Because the cells 
being studied are so early in their developmental stage, we are hopeful 
that we will be able to one day direct their development into any human 
tissue or organ. If and when scientists can specialize these cells to 
become insulin-producing islet cells, cell lines could be developed to 
produce an unlimited number of islet cells. This would effectively 
solve the islet cell supply problem.
    In addition, in most cases, the immune system of a person with Type 
1 diabetes will not tolerate an islet cell transplantation, even when 
an individual is given anti-rejection medications (which themselves can 
cause serious problems). Because stem cells are primordial all-purpose 
cells from which all tissues of the body develop, it may be possible to 
alter them genetically so that they will not be susceptible to an 
immune attack. This would negate the need for immunosuppression.
Ethical considerations
    JDF understands that stem cell research raises important ethical 
considerations that need to be addressed. However, we feel that 
appropriate safeguards can and should be established to ensure that 
this important research can be conducted using federal funding.
    The 1994 Human Embryo Research Panel, which included scientists and 
ethicists, studied the ethical issues raised by this type of research 
and concluded that stem cell research involving ``preimplantation'' 
human embryos is acceptable for federal funding. We believe that the 
Panel's report provides a scientific and ethical basis to justify 
federal funding for human stem cell research. This report could also 
serve as the basis for the establishment of a set of safeguards to 
ensure such research is conducted ethically, in both public and private 
settings, while still allowing for significant advances in the fight to 
cure diabetes.
Summary
    Mr. Chairman, the opportunities presented by human stem cell 
research offer us the promise of significant advances--and perhaps a 
cure--for diabetes. A world without diabetes for all of the children 
and adults who currently suffer from its devastating impact continues 
to be our goal, and we urge you to ensure that federal policies allow 
this research to continue to speed our path to cure this disease.
STATEMENT OF RICHARD PIKUNIS, J.D., PARKINSON'S 
            PATIENT, MARLTON, NJ
    Senator Specter. We now turn to Mr. Richard Pikunis, also a 
lawyer and a doctor, J.D., diagnosed with Parkinson's disease 3 
years ago at the age of 27, having exhibited symptoms since the 
age of 24. He persevered and received his law degree in May of 
last year at Widener University School of Law. He lives in 
Marlton, NJ, a suburb of Philadelphia, if I may say. Many of us 
consider Marltons Philadelphians. [Laughter.]
    He has one child and one on the way, and is anxiously 
awaiting a resolution of the political issues for medical 
research on Parkinson's.
    We welcome you here today and look forward to your 
testimony.
    Mr. Pikunis. Thank you, sir. My name is Richard Pikunis. I 
wish to thank Senator Specter and the other members of this 
committee for allowing me the opportunity to discuss my 
experiences with Parkinson's disease with you.
    I am not a scientist, nor do I hold myself out as an expert 
in the field of stem cell and fetal tissue research. What I can 
share with you today is my perspective as a young person with 
the terrible debilitating disease known as Parkinson's.
    Parkinson's disease is a progressive neurological disorder 
caused by the degeneration of brain cells that produce 
dopamine, a neurochemical that controls motor function. By the 
time symptoms of stiffness, tremor, and slowness of movement 
begin to exhibit themselves, the brain has already lost about 
80 percent of its dopamine-producing cells.
    Of course, I did not know any of this for a long time. 
Dopamine meant as much to me as planning for my retirement, and 
science had no bearing on my life. However, today I look to 
science praying it will be able to save my life.
    When I was 24 years old, my symptoms were apparent, but 
because of my age and general overall good health it went 
undiagnosed. I had the symptoms associated with a typical 
Parkinson's patient, slowness and loss of movement, postural 
instability, resulting in frequent falls, a distorted gait and 
muscle rigidity. I remember not going on a family vacation 
because my body ached so bad, I was so stiff and rigid, that 
walking consumed all my energy.
    Because of a common misconception that Parkinson's diseases 
is a geriatric disorder, the diagnosis was not as obvious as it 
should have been. Besides, I do not exhibit the most prominent 
telltale symptom of Parkinson's, the tremor. In fact, according 
to the American Parkinson's Disease Association, tremors only 
occur in about 70 percent of patients, and it is usually these 
tremors that bring a patient to the doctor.
    However, after years of knowing something was wrong, but 
not quite able to put my finger on it, my mind was finally put 
at ease when the doctor told me I had Parkinson's. Yes, at the 
ripe old age of 27 years, and after three medical opinions, it 
was conclusive. I did have Parkinson's disease.
    I was just starting out in life, the same age as my friends 
who were getting married and buying houses. They were enjoying 
life, as I felt life was slowly being drained from my body.
    Not knowing what Parkinson's was was probably why I was not 
as upset as my parents upon hearing the diagnosis. I remember 
my mother abruptly leaving the doctor's office, only to find 
her moments later in the car sobbing.
    Since then, I have learned a lot about Parkinson's, and I 
am here to tell you that I hate it with a passion. Parkinson's 
has robbed me of my youth. Parkinson's has been there for every 
major event of my adult life, and overshadows everything I do, 
and fights me every chance it gets. Parkinson's walked down the 
aisle with me at my wedding. It made my life hell as I attended 
law school. As if the stress of law school was not bad enough, 
I had to constantly be reminded by my stiff, aching body that 
Parkinson's was still with me.
    I had always hoped to have a career in Federal law 
enforcement when I graduated from law school, but now I am 
finding it difficult to even enjoy a walk with my family.
    I can accept all this, but what scares me the most about 
Parkinson's disease is that it holds my future in its hands. My 
son celebrated his first birthday and is learning to walk as I 
am slowly losing my ability to do so. I wake up every morning 
barely able to move until my medication kicks in.
    I am currently taking L-dopa to replace the dopamine that 
my body can no longer produce, but it is becoming less 
effective at the current dosage. I know L-dopa will not be able 
to adequately treat my symptoms forever, and it really scares 
me when I think about how my life will be in a few years if we 
do not find a better treatment or a cure for Parkinson's. I 
wonder if I will be able to teach my children how to ride a 
bike, or dance at their weddings.
    I am scared about forced retirement before I am financially 
stable. I just graduated from law school. Believe me, I cannot 
afford not to work, but I know the choice may not be mine to 
make, because with an increase in L-dopa comes the debilitating 
side effects such as involuntary body movements and motor 
fluctuations. Sometimes these side effects are just as bad as 
the disease.
    It is imperative that now, right now, we expand the 
research into Parkinson's diseases. Preliminary scientific 
evidence indicates investment in Parkinson's research, into 
areas involving stem cells and fetal tissue, have the potential 
to produce viable treatments and cures not only for Parkinson's 
disease but for heart failure, diabetes, stroke, Alzheimer's, 
and spinal cord injuries, to name a few.
    Researchers are on the cutting edge of discoveries that 
will change immeasurably the lives of millions. Please make it 
possible for the scientific community to explore these avenues 
of research. Congress has taken steps in the right direction, 
the enactment of the Morris K. Udall Parkinson's Research Act, 
but my Government is still falling short in the eyes of 
millions who desperately need their help.
    We want the money authorized by the Udall act to actually 
be spent on research. Start investing the millions it will take 
to cure us rather than the billions to care for us. Please help 
me and others like me live our dreams and maintain our dignity.

                           prepared statement

    Only you can help put an end to the human suffering 
associated with Parkinson's disease. Do not let me become a 
burden to my loved ones and society. Let me live my dream of an 
optimistic future with my wife and family.
    Thank you.
    [The statement follows:]
  Prepared Statement of the Biotechnology Industry Organization (BIO)
                           executive summary
    Pluripotent stem cells research provides the hope of a new 
generation of therapeutics. Using cell transplants instead of drugs, 
biologics and other current therapies, provides new hope for patients 
with cancer, spinal cord injury, stroke and degenerative diseases. As 
the federal government has not to date provided funding for pluripotent 
stem cell research, the biotechnology industry has taken the lead in 
funding it. For industry to continue to fund this research, and for 
this research to be developed into products at the bedside for 
patients, patent protection must be available. For the vital 
partnership between industry and academic biomedical researchers to 
remain strong, the terms of technology transfer agreements must be 
commercially reasonable.
                               statement
    The Biotechnology Industry Organization (BIO) represents 832 
companies, state and affiliated organizations engaged in biotechnology 
research on medicines, diagnostics, agriculture, pollution control and 
industrial applications. BIO appreciates the leadership of the 
Subcommittee in providing strong support for research on pluripotent 
stem cells and for this opportunity to participate in this hearing.
    Pluripotent stem cell research is a very exciting, cutting-edge 
area of scientific research whose promise has captured the imagination 
of the research community, patient advocates, and the American public. 
We urge the Subcommittee to continue to lead the way in supporting this 
research and the policies that will speed it to market for the benefit 
of patients.
    Over the last 50 years, the only constant in medical innovation has 
been that scientists are constantly trying to treat human diseases 
through new approaches. The newest approach which we are here today to 
discuss is using embryonic or pluripotent stem cells (early human 
cells) to treat degenerative cell based diseases. (We have attached to 
the end of this document two figures to help explain stem cells' place 
in embryonic development and the new method of generating these cells). 
Stem cell research is intended to find treatments which do not depend 
on chemical compounds, rather they use living cells as the treatment or 
cure.
    It is anticipated that these cells will be differentiated into 
blood, skin, heart, or brain cells and may be able to treat cancers, 
spinal cord injuries, heart disease and potentially many other 
diseases.
The science of stem cells
    There are 200 different kinds of cells that make up most of the 
human body. These cells are differentiated, which mean that they have a 
distinct morphology (shape and size), and have achieved a specialized 
function such as carrying oxygen or transmitting ``nerve'' signals. For 
years scientists have known about ``blood stem cells'' (cells that can 
become one of several different blood cells such as white blood cells 
or red blood cells) and the potential uses of umbilical cord blood.
    However, late last year the Geron Corporation announced that its 
research had, for the first time, successfully derived human embryonic 
stem (ES) cells and maintained them in tissue culture. This was a great 
step forward in this area of research.
    Stem cells are the earliest precursor of human differentiated 
cells. These cells come from an embryo, and, therefore, have been 
defined as embryonic stem cells (ES). These cells, ES cells, have the 
capacity to become virtually any cell or tissue in the body. These 
cells are ``pluripotential''--that is these cells can be used to form 
almost any tissue. These cultured ES cells are special as they have the 
capacity for self-renewal, meaning they can produce more of themselves 
without limit.
    The excitement in the research and patient community is 
understandable. There are two ways that ES cells are an advancement: 
first, as a research tool to study developmental biology; and second, 
as the starting point for therapies to create cures to some of the most 
deadly diseases. The excitement and promise of this advancement is seen 
in the letter that 52 patient and medical professional societies sent 
to Members of the Senate on December 2, 1998, which supported stem cell 
research and development (letter attached).
    Although many see the benefits of stem cell research, we understand 
that for some people this new area of research raises ethical issues. 
These issues range from the ethics of conducting research on human 
fertilized eggs to patenting research procedures.
Stem cell research
    In compliance with current law requirements and concerns of the 
public and the use of public funds to support research projects that 
raise ethical concerns, the federal government has not sponsored 
research to derive pluripotent stem cells. Now that these stem cells 
have been derived, the government is determining whether it can and 
should fund research on these cell lines.
    Recent studies have documented that government funded basic 
research is an important precursor to innovation by the 
biopharmaceutical industry. \1\ In addition, public funding stimulates 
additional investment by the drug companies and enhances the 
effectiveness of their Research and Development expenditures as well. 
\2\ According to a study of connections between pharmaceutical firms 
and publicly funded scientists in academia and government, these 
relationships have a large impact, raising the level of private sector 
research productivity by as much as 30-40 percent. \3\ (See ``Federal 
Funding for Biomedical and Related Life Sciences Research, fiscal year 
1999,'' by Federation of American Societies for Experimental Biology.) 
In addition, research that is funded by the Federal government is 
subject to a variety of oversight mechanisms.
---------------------------------------------------------------------------
    \1\ Andrew A. Toole, ``The Impact of Federally Funded Basic 
Research on Industrial Innovation: Evidence from the Pharmaceutical 
Industry,'' Madison, Wisconsin: Lauritis R. Christensen Associates 
(1997).
    \2\ Andrew A. Toole, ``Public Research, Public Regulation, and 
Expected Profitability: The Determination of Pharmaceutical Research 
and Development Investment,'' Madison, Wisconsin: Lauritis R. 
Christensen Associates (1997).
    \3\ Iain Cockburn and Rebecca Henderson, ``Public-private 
interaction and the productivity of pharmaceutical research,'' National 
Bureau of Economic Research (1997).
---------------------------------------------------------------------------
Technology partnership mechanisms
    Technology transfer is a process by which amorphous areas of 
scientific research are defined (generally through patents), then sold 
or licensed to others. This process promotes the commercial development 
of products as it is designed to provide for the capturing of the value 
of basic research by the basic researcher (generally a non-profit 
university researcher), and the shifting of the research to 
organizations that are better able to assume the financial risk 
associated with developing a commercial product (generally a 
corporation).
    In biotechnology, technology partnerships take a number of forms 
depending on whether they involve the NIH, NIH-funded research, or in 
the case of stem cell research, non-government support of research. In 
each case the biotechnology industry pays royalties for the patent 
rights to medical technologies. For your information, the principal 
technology partnership mechanisms are listed below:
    Cooperative Research and Development Agreement (CRADA).--A CRADA is 
an agreement through which researchers at the NIH and private companies 
negotiate terms for cooperative research and define the rights of the 
parties to use licenses for any patents which might be created as a 
result of the research. CRADAs are the cornerstone of the basic 
biomedical research partnerships between the NIH and the biotechnology 
and pharmaceutical industries. In many cases the corporate partner 
provides funding and other resources to conduct research at the NIH. 
This corporate partner will then take the new technology and develop a 
marketable product.
    Bayh-Dole agreements.--Bayh-Dole Agreements are agreements between 
universities or medical institutes and biotechnology companies or 
pharmaceutical companies in which the parties define the licensing 
rights to patents and agree on how to share funds and materials. 
Similar agreements exist between intramural government researchers and 
licensees.
    Technology licensing.--In the absence of federal funds, 
organizations are free to license technology as they see fit, without 
oversight of any Federal office. This freedom to license insures that 
research organizations are able to capture the value of the research. 
Generally these agreements are in accord with the mission of the 
organizations involved. Anti-trust considerations sometimes play a 
role.
Licensing of patents
    The partnerships that are formed are based upon the licensing of 
patents to basic biomedical research discoveries. These licenses are 
critical to the relationship between biotechnology and pharmaceutical 
companies and their research partners. Without patents to protect the 
taking of an invention by a competitor, a company cannot justify its 
research investment. For instance, any company would be competitively 
disadvantaged by investing in stem cell research if other companies 
could freely acquire it. It is crucial that the basic research 
institution secures patents on their inventions so companies that 
invest money in developing these inventions can benefit from their 
investment. These licenses generally require companies to make royalty 
payments to the proprietary owner of the license, or licensor, based on 
any sales of products attributed to the licensed patent. These 
arrangements allow the research organization to gain a benefit from the 
research while not bearing the risk associated with the continued and 
expensive research and development program. While protecting investment 
and rewarding risk-taking, patents also act as a powerful spur to 
competitors to improve on the patented technology or provide 
alternatives.
    In this regard, the biotechnology industry anticipates the 
assumption of the risk and hopes to pay royalties as a part of a 
license agreement. Companies frequently license technology from one 
another and the norm is to include royalty payments. Restrictive future 
licensing provisions will merely diminish the value of the licensed 
technology. Logically, in some cases, restrictive practices would 
prevent the licensing of some technology and thereby prevent its 
development.
Patents and stem cells
    Prior to the licensing of technology, the nebulous boundaries of a 
technology must be defined so that the intangible assets can be handled 
by the U.S. business and our legal system. In general that is done 
through the patent system. A U.S. patent is defined by claims that 
provide sharply defined borders to technology. These boundaries give 
clear notice to others so that the area can be avoided or licenses can 
be taken to practice what is defined. The claims can be directed to 
products and compositions of matter. Once boundaries are established 
and claims granted in an exciting field such as stem cells, patents 
provide a powerful stimulus to competitive academic groups and 
companies to improve on technologies and/or find new routes to achieve 
the same effects. In this way, patents increase the range of effective 
products available to treat intractable diseases and improve social 
welfare.
    There may be no industry which is more sensitive to patent 
protection than the biotechnology industry. The rate of investment in 
research and development in this industry is higher than in any other 
industry. Any law which undermines the ability of biotechnology 
companies to secure patent protection undermines funding for research 
on deadly, disabling and costly diseases. Capital will not be invested 
in biotechnology companies if they are not able to secure intellectual 
property protection to recoup the substantial investments they must 
make in developing a product for market.
    Our industry's position on patents follows from one simple fact 
about the biotechnology industry; most of our firms fund research on 
deadly and disabling diseases from equity capital, not revenue from 
product sales. Without investors taking the risk of buying the stock of 
our companies, much of our vital research would end. Almost without 
exception our industry cannot borrow capital. Our principal, and for 
most of us, our only source of capital, is equity capital.
    Intellectual property protection is critical to the ability of the 
biotechnology industry to secure funding for research because it 
assures investors in the technology that they will have the first 
opportunity to profit from their investment. Without adequate 
protection for biotechnology inventions, investors will not provide 
capital to fund research. There is substantial risk and expense 
associated with biotechnology research and investors need to know that 
the inventions of our companies cannot be pirated by their competitors.
    Our industry's general position on patents is identical to our 
industry's position on stem cell patents. In regard to stem cell 
research, patents are vital and they should be freely transferable. 
These patents are essential to the continuation of stem cell research. 
No money has yet been made from selling stem cell products. It is 
unreasonable to expect any money to be made for many years to come from 
this research.
Research exemptions
    This position is entirely consistent with the continued existence 
of a ``research exemption'' \4\. (This exemption is different from the 
statutory Bolar \5\ exemption that provides additional protections for 
non-patent holders. Bolar is not relevant to stem cell research at this 
time as no therapeutics are nearing submission for regulatory 
approval). The courts and BIO recognize that it is important that 
patents do not block academic research that move a field forward and 
which do not compete in the marketplace. Accordingly, the courts have 
created the ``research exemption'' as a defense against patent 
infringement for academic research--the type of research typically done 
by universities. The biotechnology industry supports this exemption. 
The industry benefits from the knowledge that is created by the 
research being done on technology that the industry has patented. This 
judicially created doctrine and the support of the doctrine from the 
biotechnology industry has in having no biotechnology company ever 
suing a university for performing academic research on patented 
technology.
---------------------------------------------------------------------------
    \4\ Popenhusen v. Falke, S.D.N.Y. 1861, 19 Fed.Cas. 1048, Northill 
Co. V. Danforth, D.C.Cal. 1943, 51 F.Supp. 928, Chesterfield v. U.S., 
1958, 159 F.Suppl 371, 141 Ct.Cl. 838, Norfin, Inc. v. International 
Business Mach. Corp. D.C. Colo., 1978, 453 F.Supp. 1072, affirmed 625 
F.2d 357, Ares-Serono v. Organon Int. B.V., D.Mass.1994, 862 F.Supp. 
603.
    \5\ Roche v. Bolar Pharmaceutical Co., Fed. Cir 1984, 733 F.2d. 858 
and see 35 U.S.C. 271(e).
---------------------------------------------------------------------------
    In large part due to the patentability of new areas of research 
like stem cell research and the transferability of patents, the United 
States leads the world in biomedical research. The competitiveness of 
the U.S. biotechnology industry means that the most vulnerable U.S. 
patients have hope. It means that they can look to American biotech 
companies to develop the therapies and cures which will ease their 
suffering.
Summary of Commercial Development Issues Regarding Stem Cell Technology
    The partnerships between NIH and NIH-funded grantees and the 
biotechnology and pharmaceutical industries stand at the center of the 
world's most productive biomedical research enterprise. Following is a 
summary of BIO's views on the commercial development issues associated 
with stem cell and other biomedical research.
  --NIH and NIH-grantees have entered into a broad array of research 
        agreements and licenses. These agreements and licenses 
        typically provide that intellectual property generated by NIH 
        and NIH-grantees is licensed or sold to biotechnology and 
        pharmaceutical companies in exchange for royalty payments on 
        any sales.
  --Central to these relationships are patents which ensure that the 
        results of the university and industry investments are not 
        misappropriated by those who did not make the investments. 
        Without patent protection no company can persuade its investors 
        to put their capital at risk, and NIH and its grantees would 
        have nothing to license. The patentability of inventions is 
        determined by the Patent and Trademark Office under well 
        established guidelines.
  --Universities filed over 3,000 new patent applications in fiscal 
        year 1997 in the expectation that they could generate revenues 
        in the form of licenses and royalties. The availability of 
        patents--which grant an inventor 17 years of protection from 
        competitors--leads to an intense competition in the development 
        of life-saving drugs, biologics and devices. Patients in need 
        of new medicines and devices are the beneficiaries of this 
        competition.
  --Patents do not block university researchers from conducting 
        research on patented inventions. These researchers are 
        protected from a patent infringement action by an 
        ``experimental use'' exemption from an infringement action 
        because they are not competitors with a commercial motivation.
  --Licenses can be exclusive or non-exclusive (i.e., sold to one, or 
        more than one entity). Each type of license may be appropriate 
        depending on the circumstances. About 10 percent of NIH's 
        licenses are exclusive. Academic researchers not engaged in 
        research for commercial use are not affected by the existence 
        of an exclusive license. The Association of University 
        Technology Managers (AUTM) Licensing Survey, fiscal year 1997, 
        found that universities executed 2,665 licenses and options of 
        which 1,377 were exclusive (52 percent) and 1,288 were non-
        exclusive (48 percent); U.S. hospitals and research institutes 
        executed 361 licenses and options, of which 208 were exclusive 
        (58 percent) and 153 were non-exclusive (42 percent); and 
        Canadian institutions executed 198 licenses and options, of 
        which 139 were exclusive (70 percent) and 59 were non-exclusive 
        (30 percent).
  --An exclusive license gives a company a greater incentive to invest 
        its resources in the development of technology and this means 
        that the companies are able and willing to pay a higher royalty 
        rate to the NIH or an NIH-grantee. Exclusive licenses are 
        particularly appropriate in cases where substantial risk and 
        expense are involved in the development of basic research into 
        a marketable product.
  --In 1997 NIH received approximately $40 million (1,000 licenses) and 
        its grantees approximately $300 million (5,000 licenses) in 
        royalties from its licenses to biotechnology and pharmaceutical 
        companies. This income helps to fund additional research.
  --In 1997, of all federally funded grantees, the top ten recipients 
        of royalty income include: University of California System 
        ($67.3 million), Stanford University ($51.7 million), Columbia 
        University ($50.3 million), Florida State University ($29.9 
        million), Massachusetts Institute of Technology ($21.2 
        million), Michigan State University ($18.3 million), University 
        of Florida ($18.2 million), W.A.R.F/University of Wisconsin-
        Madison ($17.2 million), Harvard University ($16.5 million), 
        Carnegie Mellon University ($13.4 million). This income helps 
        to fund additional research.
  --In 1996, separate from licensing royalties, industry sponsored $1.5 
        billion in research at U.S. universities, hospitals and 
        research institutes, the overwhelming portion of which is in 
        biomedical research (such as conducting clinical trials, 
        including $41 million at Massachusetts General Hospital and $26 
        million at the Mayo Clinic). This income is vital to the 
        biomedical research efforts of these institutions.
  --From 1980 through 1997 these technology partnerships between 
        federal government agencies and university-based research were 
        reported (many aren't reported) to have led to the founding of 
        1,521 U.S. companies.
  --These technology partnerships, and the patents on which they are 
        based, are particularly important to small biotechnology 
        companies. These companies tend to focus their research on 
        breakthrough technologies that come from basic biomedical 
        research. They also must have strong patent protection to 
        justify the risks they take. Most of these companies have no 
        revenue from product sales to fund research, thus, they depend 
        on venture capital and public market investors. In 1997, the 
        biotechnology industry lost $4.1 billion. Previous years have 
        had similar financial losses (1996, $4.5 billion loss; 1995, 
        $4.6 billion loss; 1994, $4.2 billion loss). The biotech 
        industry hasn't ever had a profitable year.
Conclusion
    BIO appreciates the opportunity to present these views on this 
important issue. We look forward to working with the Subcommittee to 
support policies that will speed the development of pluripotent stem 
cell research into products for the benefit of patients.

                       obtaining by ethical means

    Senator Specter. Thank you very much, Mr. Pikunis, for that 
very moving statement, and we will start now 5-minute rounds of 
questioning.
    Your testimony goes to the point that I made in my opening 
about the sense of urgency. There appears to be a ban--Senator 
Harkin may be right that there really is no ban, but NIH is 
treating it as a ban, and instead of importuning interpretation 
and litigation we have the way to resolve it with legislation 
that came out of this subcommittee.
    The purported ban, we can lift that ban, and when you talk 
about your personal situation, that is precisely the sense of 
urgency which I think ought to move the Congress to get this 
done.
    Let me ask you the first question, Dr. Goldstein. Picking 
up on your statement about obtaining by ethical means, the 
embryo is a sperm-fertilized egg and will grow into a fetus 
upon implantation in the uterus.
    What we have here are discarded embryos, so there is no 
possibility of the embryos which are used for stem cell 
research to be implanted and to produce a person, is that a 
correct scientific statement?
    Dr. Goldstein. Yes; that is our understanding of the 
situation, Senator. In addition, we presume--I presume 
personally these embryos may be damaged in handling. You may 
not want to implant them into women. Actually, to implant them 
would itself be unethical.
    Senator Specter. The long and short of it is that it is 
ethical to take these discarded embryos, which are not going to 
be used for implantation, to produce a human being for medical 
research?
    Dr. Goldstein. Yes; we believe so.
    Senator Specter. I want to turn to you, Mr. Dickinson, on 
the question of patent applicability, and again I am sorry that 
Geron is not here to give us their view of the issue.
    If the stem cell is defined as an end product, then it is 
subject to patent protection, but if it is considered to be a 
research tool, then in that situation--or is there any other 
interpretation where it would not be subject to patent 
protection?
    Mr. Dickinson. Senator, patent claims are a very arcane and 
very semantic type of----
    Senator Specter. That is why we have you here.
    Mr. Dickinson. Thank you. I think it would be not 
appropriate necessarily for me to comment on or speculate on 
what the breath of a claim might look like that we do not have 
before us at this time.
    The claims that are directed to stem cells, as you point 
out, are directed to stem cells which have been isolated and 
purified and, as such, from a long line of case law are subject 
to patent protection.
    Senator Specter. Well, if they are a research tool are they 
subject to patent protection?
    Mr. Dickinson. They can be, yes.
    Senator Specter. Under what circumstance might they not be?
    Mr. Dickinson. We have a four-part test, as I mentioned, 
for patentability, and if they are outside that test--for 
example, if they are not subject matter which is patentable by 
statute, which is a very broad statute, or if they are not new, 
if they have been known before, or if they are obvious in view 
of what has been known before, they would not be patentable.
    Senator Specter. So we might have to change the law to move 
them outside of patent protection?
    Mr. Dickinson. That is always a possibility, Senator.
    Senator Specter. Well, Congress can do that.
    Mr. Dickinson. Yes, sir.
    Senator Specter. Dr. Freire, the patent contains 11 claims, 
some of which use the term, primate to identify the Wisconsin 
work. Primate might be construed as to cover humans, although 
the term is not--the term human is not presented among the 
claims. Could that be interpreted to have any implication for 
producing human stem cells?
    Dr. Freire. Yes, Senator. We checked with the holder of the 
patent and they told us that they have prosecuted the patent to 
include humans, although none of the research supported by NIH 
was for humans. It was all for the monkeys.
    Senator Specter. Does that bear upon the issue of human 
cloning?
    Dr. Freire. Well, the claims as they are right now on stem 
cells and their production are from primates. As you point out 
and, as such, humans are primates.
    Senator Specter. My red light is on. I will pick up on my 
first question to Dr. Melton in my next round.
    Senator Harkin.

                    patentability of research tools

    Senator Harkin. Thank you, Mr. Chairman. My first question 
would be to you, Dr. Freire. You mentioned, and I caught it 
when I sat down here when I came in a little bit late, a 
dilemma. Would you expand upon what you meant by that dilemma?
    Dr. Freire. Yes; it actually bears on the question that 
Senator Specter asked Mr. Dickinson, whether or not research 
tools are patentable. They are, indeed, patentable, so the 
question is, how do you enforce those patent rights? We are 
very respectful of the patent holder's right to extract value 
from his or her invention. The concern arises when the value is 
extracted, from our perspective, at a very early stage, at the 
research stage, as we are being asked to do at this point. The 
patent, of course, as Mr. Dickinson pointed out, allows for the 
making, using, or selling, precluding others from making, 
using, or selling, and our scientists are making and using many 
of these research tools.
    When obligation is tied to these very early discoveries by 
the patent holder, at the end of the day we have a very 
encumbered potential drug or therapeutic that may never see the 
market because of these very complicated obligations.
    On the other hand, it is of value to the owner of the 
patent, and we certainly cannot diminish that value. We have 
learned very many lessons from the 20 years. Your recollection 
on Bayh-Dole is exactly correct. It was an economic development 
effort. But one of the lessons we have learned is that while we 
grant that protection we should be able to separate the way we 
license this technology to ensure that the rights to maintain 
unencumbered research continue while we extract the value for 
the commercial partner. That was not something we thought about 
doing early on.

                             bayh-dole act

    Senator Specter. Under Bayh-Dole, if the Federal Government 
is involved in any of the funding for the basic research, as I 
understand it--correct me if I am wrong--the Federal 
Government, NIH, retains the right to use those findings. Even 
though they are patentable and patented, they are able to use 
those as research tools intramurally.
    Dr. Freire. Well, we actually retain the right to use--we 
have a royalty-free right to use the patent. We have a license 
to all of those patents for Government purposes, that is, the 
intramural scientists at NIH.
    Senator Harkin. A nonexclusive right?
    Dr. Freire. That is correct.
    Senator Harkin. And it is not--well, it is not something 
that you pay for, that we pay for. The Government retains that 
right.
    Dr. Freire. Correct.
    Senator Harkin. But you can only use that for intramural--
--
    Dr. Freire. Or for Government purposes, contractual 
Government purposes, like if we have a contract and the 
contractor is doing work for the Government, that is one of the 
retained rights.
    Normally, these Government rights that are retained are not 
interpreted to ensure to our grantees. Our grantees are not 
considered part of the Government user rights.
    Senator Harkin. And you think that should be allowed? I 
mean, you raise that as a problem.
    Dr. Freire. Yes; I think that we would very much like to 
see the ability of our funded researchers to use these research 
tools unencumbered, yes.
    Senator Harkin. And if they use them unencumbered, then let 
us assume that they find an application--they are able find a 
means of developing that stem cell into muscle tissue or 
something, and you get to the Parkinson's Disease, for example, 
who has the right to that patent?
    Dr. Freire. Well, the new invention, if it is in fact a new 
invention, could be patentable by the grantee.
    Senator Harkin. Well, would the grantee then have to pay a 
licensing fee to the original patent holder of the stem cell?
    Dr. Freire. Well, what normally happens is, the grantee 
would license to company X. Company X would have to ensure that 
they have the rights to practice the invention for commercial 
purposes. Company X will go back to the companies that hold 
other rights and establish licensee agreements with the other 
commercial partners to ensure that they can move forward.
    Senator Harkin. I just want to be clear on this. My time is 
up. If the Federal Government retains the right to be able to 
use these research tools as a means of enabling our grantees--
say another university--to be able to use these as a research 
tool, that grantee is not paying any license rights to the 
initial patent holder, is that correct? That is right.
    And then the licensee develops a strain from that, and they 
then want to patent that strain and obtain the recompense for 
that. How, then, do we ensure that it gets back to the original 
patent holder that they also would retain some right in that?
    Dr. Freire. Well, the original patent holder, if they have 
a dominant patent, would be approached by the licensee who 
wants to bring the product to commercialization. Otherwise they 
would be infringing the patent of the original holder.
    Senator Harkin. I see. They could use the line for any kind 
of research, but when they take the step to commercialize it, 
then they have to go back to the original patent holder to 
obtain some rights?
    Dr. Freire. Let me clarify, Senator. In the pharmaceutical 
and biotechnology industry the research exemption really does 
not exist, per se, which is what you are getting at. We really 
do not have a very solid research exemption.
    Companies have, in fact, come back to the NIH and said, you 
need to take a license because you are making or using patented 
technology. But the pharmaceutical and biotechnology industry 
have worked with the academic sector in a hand-shake type 
agreement, because they understood the importance of basic 
science. But, we are seeing companies come back and exercising 
their rights this way.
    Senator Harkin. Thank you, Mr. Chairman.
    Senator Specter. Dr. Melton, you have extraordinary 
credentials here, with your chairmanship of the Molecular and 
Cellular Biology Department at Harvard University, and you have 
equally impressive personal interest with your 7-year-old son.
    Tell us what would the key processes be to develop stem 
cells into cells that produce insulin, or otherwise deal with 
diabetes?
    Stated differently, how close are we to using stem cells to 
solve the diabetes problem for your son?
    Dr. Melton. That is a very good question, Mr. Chairman. 
What I can tell you with some confidence is that the work with 
mouse stem cells is so encouraging that one is within a few 
years of being able to get those cells, or direct them to 
become pancreatic cell types in culture, and that is why I 
think it is so imperative that we immediately begin to transfer 
that information, to test our knowledge, in the case of the 
human cells to determine whether there are any significant 
differences.
    I was very encouraged by that questioning, because it is 
clear that you and Senator Harkin are trying to free up Federal 
funding so that this sort of research can continue.
    Senator Specter. Well, as you know, there were many 
millions of dollars added by this subcommittee last year, but 
it does not do a whole lot of good if the NIH is barred from 
using that on this very dramatic breakthrough.
    Dr. Melton. What I can see, speaking from the scientist's 
point of view in the trenches, is that there are many people 
with very good ideas, novel ideas about how to actively pursue 
this research, and we are anxious for Federal funding.
    Senator Specter. Your few years is very helpful. We do not 
have a whole lot of time, so I am going to move on to Mr. 
Pikunis.
    On Parkinson's, there have been very effective advocacy 
groups. With the Udall legislation last year, that sort of took 
the Congress by storm on the difficult matter of having 
Congress establish priorities, which are characteristically 
left for NIH.
    Just how pressing is it for you personally, Mr. Pikunis, in 
terms of your daily activities, to have the assurance that NIH 
will move forward, the Federal Government will move forward? 
How does that impact on your daily life?
    Mr. Pikunis. I think it is very important, because right 
now under current medication-type treatments for Parkinson's 
Disease I am fine as long as I am on the medication, but I 
notice if the dosage goes too high I start exhibiting the side 
effects of the involuntary body movements, and that is at a 
slightly increased dose from what I am on now.
    As long as I am on the current dose, I am fine, but I know 
that the current does is not going to last me forever.
    Senator Specter. Dr. Goldstein, you identified a range of 
other ailments in your testimony, heart disease, Alzheimer's--
does this have application for cancer as well?
    Dr. Goldstein. Yes; we believe it does. Many of the 
therapies that are involved in cancer chemotherapy wipe out 
many types of cells in the body that need to be replenished. 
Often, they are done by bone marrow transplants. Stem cells 
could, in fact, be a much better source of these vital cells.
    Senator Specter. Dr. Melton gives us a few years, as he 
says, with respect to diabetes. Would you give us a ball park 
figure with respect to Alzheimer's?
    Dr. Goldstein. Alzheimer's is a very tough problem, 
Senator, and I do not think we have a very good sense of how 
long it will be. I guarantee you that every day we delay is 
another day that the clock ticks and we are not making progress 
using this vital research need.
    Senator Specter. People in Congress like to have figures, 
even ball park figures. Let me press you on the question, and 
very seriously, this business of advocacy is a very tough 
issue.
    The first thing we have to do is disabuse many of the 
notions that using embryos is somehow related to destroying 
human lives. That is a very, very big political issue, and you, 
ladies and gentlemen, a pretty good-sized group here, ought to 
be aware of that in terms of your advocacy. You have got to 
approach a lot of people to disabuse that notion.
    And then if you talk in terms of being close, and what the 
dollars will do, then you start to create an impetus for it, so 
I want to give you just a little insight into advocacy.
    My red light is on, but yours is, and for a very short 
answer, how long?
    Dr. Goldstein. Maybe 5 to 10 years, Senator, where we could 
see some hope. We can turn these cells into neurons now, but 
the question is whether we can turn them into the right sorts 
of neurons.
    Senator Specter. Senator Harkin, as is not unusual, has the 
last word. [Laughter.]

                    University of Wisconsin research

    Senator Harkin. Again, Dr. Freire, in your testimony you 
mentioned that because the Government funded earlier research 
on rhesus monkeys at the University of Wisconsin the Government 
has a ``nonexclusive royalty-free right to use the patented 
cells by or on behalf of the Government.'' Do those patented 
cells include human embryonic stem cells?
    Dr. Freire. The owner of the patent would argue that they 
do include human embryonic stem cells.
    Senator Harkin. The owner of the patent?
    Dr. Freire. Wisconsin.
    Senator Harkin. That they do?
    Dr. Freire. Yes; that the claims to that patent do include 
human embryonic stem cells. The word human does not appear in 
the claims. The word primate appears in the claim, and primate 
encompasses humans. That is the way the owner of the patent 
prosecuted this application, from what we have been able to 
discuss with them.
    Senator Harkin. Do you agree with that?
    Dr. Freire. Yes.
    Senator Harkin. Mr. Dickinson, some in the research 
community argue the Patent Office is issuing biotechnology 
patents that are too broad. What is your response to that?
    Mr. Dickinson. Well, the matter of the breadth or the 
narrowness of the claim is a matter, again, of matching it up 
against those four statutory requirements that I mentioned.
    It has been my experience that when patents issue of a 
certain breadth in a new technology there is often concern 
about that breadth, but what happens in reality is that 
additional patents, what may be called a genus patent, what 
often happens, very quickly, is the people develop species 
patents, new and not obvious claims in new patents that would 
be patentable over that original broad patent.
    This is something we have dealt with historically. It has 
been dealt with effectively.
    Senator Harkin. You do not think they are too broad?
    Mr. Dickinson. Not in general, no. The nature of the 
breadth of a patent is measured by the prior art.

                               Bayh-Dole

    Senator Harkin. My time is up. One final question for all 
of you. Do we need to readdress Bayh-Dole?
    I have heard that it has been a success, but like anything 
that is 18 or 19 years old, it may need to be readdressed. Do 
we need to make some changes, because the biotech industry had 
not really started--it was in its embryonic stage when we 
passed Bayh-Dole.
    Do we need to make any changes in Bayh-Dole, Dr. Freire?
    Dr. Freire. When I discuss this with my colleagues at 
universities the president of the Association of University 
Technology Managers Karen Hersey said publicly that perhaps 20 
years later we could go back and look and see how some of these 
things have worked, so it would not be a full rewriting but an 
assessment. I think it would be responsible to take a look at 
what those items are.
    Senator Harkin. Well, I for one, just speaking as an 
individual, am open to any suggestion from you or anyone else 
in the audience about suggestions for modifications if 
modification is needed. I have not made that decision yet.
    Mr. Dickinson, what say you?
    Mr. Dickinson. I am not an expert on the Bayh-Dole Act. It 
is probably not my place to comment on whether it is working or 
not.
    Senator Harkin. Dr. Goldstein, how about you? What do you 
say?
    Dr. Goldstein. I am sorry, Senator, I am not a lawyer, but 
I can certainly point out that it is always worthwhile 
reviewing past actions after 20 years have passed.
    Senator Harkin. Dr. Melton, do you have any views on that?
    Dr. Melton. I agree with Mr. Goldstein that the rapid 
changes in the biotech industry were not foreseen when that act 
was constructed and I think it is worth revisiting it.
    Senator Harkin. Mr. Pikunis, do you have any views on this?
    Mr. Pikunis. No, sir; I do not.
    Senator Harkin. I am just trying to figure out--and again, 
the dilemma is, we want the research, we want the money 
invested, we want private moneys invested, and we also want to 
make sure that they are able to get a return on that investment 
and that they are able to patent it, but we also want to make 
sure the research is broadly and widely available to others, 
and that we are not hindered by a broad patent that is issued 
that hinders further research that may be utilized. That is the 
dilemma.
    But I do not know what we will do on the Bayh-Dole Act, Mr. 
Chairman. I do not know if it needs to be looked at or not. 
Like I say, I have personally made no decision on that.
    Senator Specter. Senator Harkin, it may be we will have to 
take a look at it, and we will have to take a look at the 
patent laws, or it may be that if Congress takes a look at the 
patent laws in the Judiciary Committee, that there will be a 
little more generosity on licensing, and having research going 
forward. You never can tell how those issues are going to 
interact.

                          subcommittee recess

    Thank you all very much for being here, that concludes our 
hearing. The subcommitee will stand in recess subject to the 
call of the Chair.
    [Whereupon, at 10 a.m., Tuesday, January 12, the hearing 
was concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]


                  STEM CELL RESEARCH: HHS LEGAL RULING

                              ----------                              


                       TUESDAY, JANUARY 26, 1999

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 9:03 a.m., in room SD-138, Dirksen 
Senate Office Building, Hon. Arlen Specter (chairman) 
presiding.
    Present: Senators Specter, Harkin, and Hollings.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENTS OF:
        HAROLD VARMUS, M.D., DIRECTOR, NATIONAL INSTITUTES OF HEALTH
        HARRIET RABB, J.D., GENERAL COUNSEL, DEPARTMENT OF HEALTH AND 
            HUMAN SERVICES

                       NONDEPARTMENTAL WITNESSES

STATEMENTS OF:
        ERIC M. MESLIN, Ph.D., EXECUTIVE DIRECTOR, NATIONAL BIOETHICS 
            ADVISORY COMMISSION
        RICHARD M. DOERFLINGER, ASSOCIATE DIRECTOR FOR POLICY 
            DEVELOPMENT, SECRETARIAT FOR PRO-LIFE ACTIVITIES, NATIONAL 
            CONFERENCE OF CATHOLIC BISHOPS

                   opening remarks of senator specter

    Senator Specter. Good morning, ladies and gentlemen. The 
Subcommittee on Labor, Health and Human Services will proceed.
    We have scheduled this hearing on stem cells, which is the 
third in reasonably rapid succession, given the hearing 
schedules of the subcommittee, this subcommittee or any 
subcommittee, because of the importance of stem cells research, 
where there is such enormous potential for medical advances.
    The request has been made that the subcommittee not proceed 
to initiate legislation on the subject because that might 
complicate the use of stem cells under an opinion which has 
just been rendered by legal counsel for the Department of 
Health and Human Services, and we want to work with HHS and NIH 
to see to it that the most appropriate course is followed here.
    The definition of ``organisms'' and ``stem cells'' and the 
entire medical lexicon is extraordinarily complicated. We have 
noted that NIH researchers will only be allowed to work on stem 
cells obtained by private sources. No NIH-supported researchers 
will be allowed to conduct direct work on a human embryo, even 
to obtain stem cells, consistent with the existing ban.
    That is an advance, but it is limited, obviously, on the 
face. There are a series of NIH caveats in that NIH will not 
fund any human cell research until such time as special 
guidelines are developed addressing relevant ethical and moral 
issues. So that is a constraint.
    NIH plans to convene a special oversight group to review 
all research grant applications involving human stem cells in 
addition to the regular scientific review process, which is 
another limitation. NIH has asked the National Bioethics 
Advisory Board for additional guidance.
    I appreciate the thinking of NIH on all these very complex 
subjects. The hearing today will focus on to what extent that 
may delay research, and there is a question as to whether 
additional legislation is needed, which we will be addressing. 
These are very, very difficult legal problems, and that only 
begins to scratch the surface of the ethical problems which 
underlie them.
    The question is in my mind as to whether legislation is 
necessary or desirable. Maybe we should not have any 
legislation. My preliminary thinking is, as I expressed it in 
the second hearing, after studying the issue from our initial 
hearing, was that we really ought to utilize this kind of 
research, and if it requires legislative change then I think we 
ought to proceed in an expeditious way, but in a careful way.
    So Dr. Varmus, that is a very, very brief outline of some 
of the problems running through my thinking on it. We welcome 
you here again today. I know that there are scheduling problems 
among the panel and there is a scheduling problem with the 
subcommittee. We have advanced the hearing, as you know, to 9 
o'clock because we have a caucus on the impeachment case, which 
is very time-consuming. But it is my firm view that we ought to 
be taking care of other problems as well. So whatever time we 
have to meet to do that, however, we can proceed in an 
appropriate but expedited fashion, we intend to do that. I know 
you are experienced at that, Dr. Varmus.
    We thank you for coming. We compliment you again on the 
outstanding work you have done at NIH over the years. We have 
put the government's money where our praise is, to paraphrase a 
famous statement. The floor is yours, Dr. Varmus.

                 SUMMARY STATEMENT OF DR. HAROLD VARMUS

    Dr. Varmus. Mr. Chairman, thank you very much.
    Senator Specter. I would like you to limit the opening 
statements to 5 minutes, to leave maximum time for questions.
    Dr. Varmus. I appreciate your attention to these issues 
despite conflicting demands on your time.
    My purpose today is threefold. I want to just say a couple 
of words to remind you about the scientific prospects here, 
review the legal decision that you have alluded to, and outline 
the next steps that the NIH proposes to take to pursue our 
intention to support research with these new stem cells.
    I remind you that human pluripotent stem cells were 
recently isolated by two methods: first from fetal tissue after 
elective abortion; and from embryos that were donated after 
treatment of infertility. Neither of these events were 
supported with Federal funding.
    Now, human pluripotent stem cells can divide in culture for 
long periods. That is part of their usefulness--good morning, 
Senator--and they have the potential to form virtually any kind 
of tissue. The research applications of these cells are various 
and important. They include attempts to understand human 
development, efforts to develop drugs and test for drug 
toxicity in new ways, and the potential for developing cell 
therapies for many diseases, injuries, and conditions.
    We discussed in December at your hearing the issue of 
Federal support for this science and indeed other kinds of 
science as well. As you heard from the panelists at that time, 
there are several advantages to receiving Federal support in 
this area: the open exchange and the more intense and 
accountable oversight, the greater number of dollars and the 
more talent recruited to these problems, and the ultimate goal 
of faster progress toward public health goals.
    We at the NIH respect and recognize many ethical and legal 
concerns about human pluripotent stem cells and the modes by 
which they are derived. We are firm in our conviction that 
Federal funds should not be used for this purpose until both 
the legal concerns and these ethical concerns have been 
addressed and many constituencies, including Congress and the 
public, have been consulted.
    As a first step, I asked the General Counsel, Harriet Rabb, 
who is sitting with me today, for a legal opinion about the 
Federal funding of research with these cells, distinguishing 
carefully between the use of the cells and their derivation. In 
other words, can we support work with the established human 
pluripotent stem cells in view of the appropriation law that 
you alluded to that bans the use of Federal funds for embryo 
research.
    The essence of her opinion, which you have been given, is 
that: first, yes, we can fund work with human pluripotent stem 
cells derived from nonliving fetuses under the existing 
statutes that govern fetal tissue research; secondly, that we 
can fund work with human pluripotent stem cells that are 
derived from embryos because the cells themselves are not 
organisms, they cannot become organisms, and hence they are not 
embryos as defined by law. Indeed, at your December hearing, 
prompted by Senator Harkin, all witnesses who expressed an 
opinion agreed with this definition.
    Now, under the appropriation law it is also the case that 
we cannot use these stem cells to make an embryo, for example 
by somatic cell nuclear transfer, and of course we cannot fund 
work to derive such cells from embryos, although we can do so 
from fetal tissue.
    I presented these views at a meeting of the National 
Bioethics Advisory Commission on January 19. That meeting was 
held on this topic in response to a presidential request that 
the entire area of stem cells research be reviewed in view of 
the promises of recent work, because he felt that recent 
advances had indicated that there was a need to reassess the 
balance between the ethical concerns about such work and the 
promise for medical research.
    We welcome the review by NBAC. We specifically seek prompt 
guidance with respect to the ethical considerations that will 
allow us to carry out appropriate oversight on this research.
    What are our next steps? Well, first, as I have made clear 
on many occasions, no immediate funding is occurring until we 
have our guidelines and process in place. This has been 
communicated to all of our investigators, both intramurally and 
extramurally, through memos and Internet postings and news 
reports.
    Second, I am establishing a working group of my advisory 
committee to the Director which has ad hoc members from all the 
relevant specialties. That working group will work with NIH 
staff to compose guidelines for the conduct of research on 
these cells. The guidelines will address the work to be done 
with the cells, how the cells were derived, and how the 
starting materials were obtained.
    There are important frameworks that will make this 
formulation of guidelines easier. There are Federal rules for 
work with fetal tissue that will be helpful. Some years ago, in 
1994, a human embryo research panel issued recommendations that 
were extremely thoughtful and will be important guides in the 
development of guidelines.
    Finally, the group will also be consulting with the NBAC, 
with Congress, with the public. We will be publishing a draft 
of our guidelines in the Federal Register for comment. We 
expect to have the guidelines written and presented to the 
public in the course of the next couple of months. We will then 
promulgate those guidelines and then, in a manner to be 
determined by the working group, an oversight group will ensure 
that all who do this work are actually in compliance with the 
guidelines.
    We expect that the vast majority of applications will be 
mostly routine. That is, they will be applications to work with 
the existing cells that have been described and whose 
provenance is well understood. Any uncertainties will be 
referred to further public discussion and we will carry out 
annual reporting to Congress and the public about the status of 
the science, the number of investigators, and any change 
proposed for the guidelines.
    Before I conclude these remarks, let me just make a 
personal comment, that since I made my presentation to NBAC 
last week my staff and I have received many, many, thoughtful, 
interesting, perplexing questions. Let me just address two of 
those that I think will help inform our discussion.
    First, we have been asked, is not working with these stem 
cells like using stolen goods because some of them were derived 
from embryos in that embryo research is forbidden? No, no. It 
is not illegal to derive human pluripotent stem cells. What is 
forbidden is the use of Federal funds to derive them from 
embryos.
    In this sense, it is like many legal activities for which 
Federal funding is not permitted. No Federal funds were used, 
no laws were broken, in producing these stem cells, and we have 
determined that no laws would be broken if Federal funds are 
used to support work with them once they have been derived.
    The second question we frequently hear is, will not Federal 
funding for human pluripotent stem cells create a demand to 
create additional human embryos? Again the answer is no. There 
are thousands of embryos, indeed probably tens of thousands of 
embryos, that are frozen and discarded in the United States in 
vitro fertilization clinics each year because they are in 
excess of the number required for successful treatment of 
infertility.
    In contrast, human pluripotent stem cells derived from very 
few embryos can be used by many investigators for hundreds of 
experiments because it is usually possible to keep these cells 
growing for many generations, that is for many cell doublings.

                           PREPARED STATEMENT

    Furthermore, Federal guidelines that protect against 
coercion in the procurement of fetal tissue are likely to be 
emulated in the construction of our guidelines for work with 
human pluripotent stem cells.
    Mr. Chairman, no doubt you and Senator Harkin have other 
questions. I would be pleased to answer them now. Thank you 
very much.
    Senator Specter. Thank you very much, Dr. Varmus.
    [The statement follows:]
               Prepared Statement of Harold Varmus, M.D.
    I would like to thank you for the opportunity to discuss the recent 
decision by the Department of Health and Human Services concerning HHS 
funding for research utilizing human pluripotent stem cells. In 
testimony to this Subcommittee on December 2, 1998, I presented the 
exciting science of human pluripotent stem cells and described how the 
isolation of these cells could radically change the landscape of 
biomedical research. At that time, the NIH was awaiting a legal opinion 
from DHHS to determine whether or not the NIH could fund research 
utilizing these cells. The legal opinion is now available and states 
that research utilizing human pluripotent stem cells can be supported 
with Federal funds. What then are the next steps?
    First, let me say that we understand and respect the different 
points of view that have been expressed about the important ethical and 
moral issues involved in this research. In developing the important 
safeguards that will govern funding for this research, NIH intends to 
consult with those representative of a broad range of views. We welcome 
the input of Congress as we move forward in this area.
    Today, I would like to very briefly review some features of human 
pluripotent stem cells--how they are derived and the promises they hold 
for medical research and practice. I will then describe the legal 
opinion and the plans for the development of guidelines and oversight 
that will be in place before NIH would fund research with these cells. 
We are committed to proceeding in a careful and deliberate manner that 
recognizes the ethical, societal, and scientific issues of this area of 
research.
    I refer you to my previous testimony for a fuller description of 
the scientific aspects of this research. Stem cells are cells that have 
the ability to reproduce themselves and to give rise to other more 
specialized types of cells. Totipotent stem cells--such as the product 
of fertilization of an ovum and its progeny--are stem cells that have 
total potency, which means that they have the ability to form an entire 
mature organism, e.g., a human being, although only if placed in a 
woman's uterus. In contrast, human pluripotent stem cells, which are 
under discussion today, do not have total potency, and hence cannot 
form an entire organism under any known condition. But pluripotent stem 
cells can give rise to all of the different types of specialized cells 
in the body.
    The methodologies for deriving human pluripotent stem cells are not 
really new; pluripotent stem cells have been derived from mice since 
the early 1980s and, since then, from non-human primates and other 
animals. The first reports of deriving human pluripotent stem cells 
were published in November 1998 by Dr. John Gearhart and Dr. James 
Thomson. Neither of these investigations were supported with DHHS 
funds, although Dr. Gearhart's work could have been supported with 
Federal funds, because he and his colleagues derived human pluripotent 
stem cells from primordial gonadal tissue which was taken from a non-
living fetus. Federal laws and regulations already exist that govern 
research on fetal tissue. Dr. Thomson and his co-workers derived 
pluripotent stem cells from the blastocyst stage of an early embryo--
the embryos used were donated by couples who were receiving infertility 
treatment; this derivation of stem cells from the embryo does fall 
under the ban on Federal funding in the HHS/Labor/Education 
Appropriations Bill. The pluripotent stem cells derived by each of 
these means appear to be very similar or identical in structure, 
function, and potential; but it will take more research to verify this.
    The isolation and culturing of human pluripotent stem cells opens 
certain avenues of research for the first time. Let me mention just 
three potential applications of human pluripotent stem cells. The first 
is research focused on how stem cells differentiate into specific types 
of cells. The goal is to identify the genetic and environmental signals 
that direct the specialization of a stem cell to develop into specific 
cell types. Studying normal cell and tissue development will provide an 
understanding of abnormal growth and development which, in turn, could 
lead to the discovery of new ways to prevent and treat birth defects 
and even cancer.
    A second and more practical application of research using these 
cells is in pharmaceutical development. Use of human pluripotent stem 
cells could allow researchers to study the beneficial and toxic effects 
of candidate drugs in many different cell types and potentially reduce 
the numbers of animal studies and human clinical trials required for 
drug development.
    The third and most obvious potential application of these human 
pluripotent stem cells is to direct the specialization of the cells 
into cells and tissues that could be transplanted into patients for the 
purpose of repairing injury and pathological processes. A number of 
such examples are described in my December testimony, but two are worth 
mentioning here.
    (i) Transplantation of healthy heart muscle cells could provide new 
hope for patients with heart disease. The hope is to develop heart 
muscle cells from human pluripotent stem cells and then transplant them 
into the failing heart muscle in order to augment the function of the 
heart. Preliminary work in mice and other animals has demonstrated that 
healthy heart muscle cells transplanted into the heart successfully 
repopulate the heart tissue and integrate with the host cells. These 
experiments show that this type of transplantation is feasible.
    (ii) In many individuals with Type I diabetes, the production of 
insulin in the pancreas by specialized cells called islet beta cells is 
disrupted. There is evidence that transplantation of either the entire 
pancreas or isolated islet cells could mitigate the need for insulin 
injections. Islet cell lines derived from human pluripotent stem cells 
could be used for this critical research and, ultimately, for 
transplantation.
    Because human pluripotent stem cells continue to replicate 
robustly, stem cells derived from a few embryos or from a few fetuses 
could potentially be used in hundreds of individual research protocols.
    Briefly, that is the science and the promise. We are here today to 
discuss the role of the Federal Government in the future of this area 
of research.
    There are a number of advantages to using public funding for 
research. Perhaps the most important reason is the fact that Federal 
involvement creates a more open research environment--with better 
exchange of ideas and data among scientists--more public engagement and 
more oversight. In addition, Federal support increases the fiscal 
resources and expands the pool of talented investigators--particularly 
in academia--both of which accelerate the tempo of scientific 
discovery.
    In response to the recent announcements concerning the isolation of 
human pluripotent stem cells, I requested an opinion from DHHS on the 
legality of using DHHS funds to support or conduct research that 
utilizes these cells, in light of existing restrictions on human fetal 
tissue research and the amendment in our Appropriations bill governing 
human embryo research.
    On January 15, 1999, DHHS delivered the following opinion. DHHS 
funds can be used to support research utilizing human pluripotent stem 
cells that are derived from human embryos: the statutory prohibition on 
human embryo research does not apply to research utilizing human 
pluripotent stem cells because human pluripotent stem cells are not 
embryos. The statute that bans the use of Federal funds for embryo 
research defines embryo as an organism derived by fertilization and 
other means. The statute does not, however, define organism. Therefore, 
the legal opinion relied on the broadly accepted science-based 
definition of organism: an individual constituted to carry out all life 
functions. By this definition--and as you heard from all the witnesses 
that responded to that question at your hearing on this matter on 
December 2, 1999--pluripotent stem cells are not and cannot develop 
into organisms. Therefore, human pluripotent stem cells are not embryos 
and are not covered by this prohibition on Federal funding. In 
addition, the legal opinion states that DHHS funds can be used for 
research using human pluripotent stem cells that were derived from 
fetal tissue if the existing laws and regulations governing fetal 
tissue research are obeyed.
    Now that the legal opinion has been rendered, what are the next 
steps? The approach will be careful and deliberative, recognizing the 
important ethical concerns that surround this area of research. I want 
to emphasize that NIH will not use Federal funds for research using 
human pluripotent stem cells until guidelines and procedures to oversee 
the research are developed. Let me describe the process that we have 
planned to ensure that any research involving human pluripotent stem 
cells is appropriately and carefully conducted. And as I mentioned 
earlier, we are interested in hearing a broad range of views.
    First, all researchers currently receiving NIH support have been 
notified, via the NIH web site, that they cannot use DHHS funds to 
begin research using human pluripotent stem cells until further notice. 
We have made every effort to include this policy in all of our public 
statements. In addition, NIH program staff have been requested to 
notify those grantees who are most likely to have an interest in this 
work about this present policy. The Deputy Director for Intramural 
Research has also notified intramural scientists of these requirements.
    Second, I will convene a subcommittee of the Advisory Committee to 
the Director (ACD) to develop Guidelines that specify what work using 
these cells can and cannot be supported with DHHS funds and outline 
restrictions on the use of such funds in the derivation of the cells. 
They will also be asked to develop an oversight mechanism to review 
research proposals seeking to conduct research utilizing these 
pluripotent stem cells. The subcommittee will meet in public session 
and will be composed of scientists, the lay public, ethicists, and 
lawyers; former members of the Human Embryo Research Panel may be asked 
to participate. They will be asked to consider advice from the National 
Bioethics Advisory Commission (NBAC), the newly established Council of 
Public Representatives (COPR), the public, and the Congress. NIH 
already has two thoughtful sets of Guidelines which will inform these 
efforts--the 1994 Report of the Human Embryo Research Panel and the 
regulations regarding Research on Transplantation of Fetal Tissue 
(section 498A of the Public Health Services Act). Once developed, 
Guidelines for research utilizing human pluripotent stem cells will be 
published in the Federal Register for public comment. We hope the 
Guidelines and oversight process will be operational within the next 
several months.
    In conclusion, the promise of human pluripotent stem cell research 
is great. And we are committed to addressing important issues 
surrounding this research in a deliberative and careful process to 
ensure that this research is conducted in an ethical, scientifically 
valid, and legal manner.
    This concludes my statement. I would be pleased to respond to any 
questions you may have.

                   SUMMARY STATEMENT OF HARRIET RABB

    Senator Specter. Before yielding to my distinguished 
colleague, we are going to turn to Dr. Rabb. We appreciate your 
being here, Dr. Rabb. You served as General Counsel for the 
Department of Health and Human Services since May 1993, a very 
substantial tenure; former director of clinical education of 
Columbia Law School, vice dean of the law faculty in 1992. We 
appreciate your joining us and the floor is yours, Dr. Rabb.
    Dr. Rabb. Thank you, Senator.
    I wanted to spend the time today answering your questions, 
if I may. You have my legal opinion. It is available to you for 
any questioning you would like to put to us. I felt we should 
save the time if you do not mind.
    Senator Specter. I understand you are waiving your opening 
statement?
    Dr. Rabb. If you do not mind.
    Senator Specter. Okay. Let me turn at this point to my 
distinguished colleague, Senator Harkin.

                     REMARKS OF SENATOR TOM HARKIN

    Senator Harkin. Thank you, Mr. Chairman. Again, thanks for 
holding this follow-up hearing. This is an area that captured 
my imagination and I think it is one of the most exciting new 
realms that we have in science, that just holds so much 
promise. That is why I am just delighted that we got your 
decision, Dr. Rabb, on this that this research could proceed 
apace.
    I congratulate you, Dr. Varmus, on setting up the 
subcommittee to do this in a careful procedural, open way so 
that the public is aware of what we are doing. There is, as you 
know, a lot of concern about this. There are ethical 
considerations. I do not downplay those at all. As I have said 
before on many occasions, I believe that science, especially in 
this area, holds so much promise for alleviating human 
suffering and debilitating disease that we have to move ahead 
aggressively, although, again as I have said, we have to be 
careful about the ethical considerations.
    I believe that scientists working with ethicists and 
lawmakers together, getting good public input, I believe we can 
craft--I believe we have, I believe you have, Dr. Varmus. I 
think we have a great structure to this.
    As I understand it, your guidelines will be out in a couple 
of months. That was the first question I had, but you answered 
it. In a couple of months you will have these guidelines ready 
to go. I assume then that funding could then proceed after 
that, I would hope.
    Dr. Varmus. We will submit for public comment, Senator. We 
will submit for public comment, for 30 days of public comment.
    Senator Harkin. I see. I am just wondering. Do you have any 
idea right now--I am certain requests must be coming in as we 
sit here.
    Dr. Varmus. Yes, correct.
    Senator Harkin. What sort of backlog do you see out there, 
requests coming in for this kind of thing?
    Dr. Varmus. Well, I have only indirect information. Recall 
that there will be three ways at least to support this 
research. Some investigators already have grants and they may 
be working in this general area, but want to shift their 
emphasis to work with human stem cells. There will be others 
who may want to supplement existing grants by a small research 
application. Others may want to initiate a new grant. In 
addition, we have intramural investigators who may be 
interested.
    The only way we have to gauge the level of interest at this 
point is to ask Doctors Thomson and Gearhart, who have made 
these cell lines, how many requests they have received. We know 
they have received on the order of 50 to 100 requests from 
various investigators for these cells to be worked with. But 
the investigators have been informed that at this point NIH 
funding is not to be used until we have our procedures in 
place. We hope, as I say, that that will be within the next few 
months.
    Senator Harkin. Well, I appreciate that. Again, I am 
grateful for your opening statement in terms of addressing 
head-on this issue of encouraging the creation of embryos. I 
have heard a lot about that. But as you point out, because of 
in vitro fertilization we have a lot of those, plus the fact 
that the cells can continue on. So I do not think there is any 
problem there at all. I am happy that you addressed that issue.
    I just, I guess I have less than a question. I just 
encourage you, Dr. Varmus--I do not think you need any 
encouragement in this area, but--to really push ahead in it. I 
mean, the more reading I do on this--I am not a scientist, but 
the more reading I do on this, this holds so much promise, and 
it could be in not too long a time for people suffering from 
Parkinson's or heart disease, just understanding cancer cell 
biology for example, things like that, that we just have not 
had that grasp on right now.
    I just again hope that you will proceed apace and keeping 
in mind the guidelines, the need for public input and openness, 
ethical guidelines. All that taken into account, I just hope 
you will do everything you can to get the funding out to the 
researchers. If we need to do anything here in the 
subcommittee--I know Senator Specter has gotten us a whole lot 
more money to put into medical research this year. So if you 
need any more of that money, we can maybe help out.
    I am putting you in a tough spot. But I hope we can get 
more. We are working together on that. I think the budget from 
the administration is going to be woefully inadequate to meet 
the needs that we have out there and I am hopeful that we can 
get more.
    So any information that you have on the need for this for 
the members and our responsibilities here for funding, I 
encourage you to let us know.
    Dr. Varmus. I will do that, Senator. Thank you.
    Senator Harkin. Thank you, Dr. Varmus.
    Thank you, Dr. Rabb, for the issuing of the opinion in a 
timely manner.
    Senator Specter. Dr. Varmus, I begin with a baseline 
question. Just what is the extent of the potential, in your 
professional opinion, from the stem cells? We have heard very 
extraordinary comments about potential on Alzheimer's and 
Parkinson's and diabetes, cancer, heart ailments, a whole range 
of human medical problems. You are the great expert, Director 
of NIH. Is that potential accurately stated?
    Dr. Varmus. Well, no doubt, as in all realms of discussion 
of this topic, there may be some hyperbole. But much of it is 
in my view accurate. We have experience with similar work done 
in experimental animals, for example in mice, and we know that 
it is possible--we have had a long experience now, nearly 18 
years or so, working with the parallel types of cells, 
pluripotent stem cells from mice, and we know that those cells 
can be induced to differentiate into certain kinds of cells and 
those cells can be used to replenish diseased or impaired or 
missing cells in mouse models of disease, that the prospects 
for repairing damaged hearts and treating congestive heart 
failure, for example, for returning missing components of the 
blood system, are all very real.
    There will be difficulties in treating more complex 
diseases, like Alzheimer's. I do not think we should minimize 
the challenge there. However, in conditions like diabetes, 
where we know one specific type of cell is missing and that 
that cell produces a product which circulates in the body, I 
think the prospects are great.
    As I emphasized last time, there are two major impediments 
to using these cells in cell therapy. One is that we have a 
still very limited idea of how to take mass cultures of these 
cells and direct them efficiently into one cell lineage. But 
that information will come as we study the way in which these 
cells undergo their changes in program that allows them to 
select a cell type to become.
    The second problem is one of rejection, histocompatibility, 
the classic problem in transplantation. We know that those 
problems may be at different levels of severity with different 
tissues. We also know that there are ways to manipulate cells 
in culture to make them seem less foreign to the host.
    Furthermore, there are new methodologies that are in 
development that could obviate these problems in other ways, 
for example by using our understanding of how cells work and 
their apparent plasticity to take one kind of cell from the 
patient himself or herself and to remodel that cell to make it 
able to replace diseased or absent tissue.
    Senator Specter. Dr. Varmus, you say that diabetes--you 
single that out as one which is closer to solution. I know from 
time to time we press you unduly as to a time frame, maybe not 
unduly but we press you, because that is a very strong argument 
with our colleagues to get additional funding if you can put it 
in a time frame.
    Could you give us a ballpark figure as to, say diabetes, 
when this research might produce the cure?
    Dr. Varmus. Well, as you know, Senator, I tend to be more 
conservative than some of my colleagues in making these 
predictions. But in the case of type one diabetes, where we 
know that replenishment of the beta cell, of the Islets of 
Langerhans in the pancreas, does have an important positive 
effect in some patients who have been treated, for example, 
with pancreatic transplantation.
    In that setting, where we know what we need to do, the 
major challenge is to figure out a way to make a pluripotent 
cell become a beta cell.
    Senator Specter. Could you give us a ballpark figure as to 
how long?
    Dr. Varmus. I would say certainly no sooner than 5 years, 
but beyond that I am guessing.
    Senator Specter. Let me ask you now about when these 
guidelines will be out and when you will be able to start using 
funds for research. You have a whole series of preliminaries, 
the special guidelines, the oversight group, additional 
guidance from the National Bioethics Advisory Board, a comment 
period.
    When? I approach this question with a sense of urgency 
because, and I do not think it is hyperbole to say, that every 
day lost human lives are lost. So when?
    Dr. Varmus. I share your concern, Senator. But I do think 
it is important to have an open and fair process because of the 
many concerns that are felt and the feeling that the public and 
Congress want to have a chance to express their opinions.
    I am currently assembling the group that will work with us 
to establish the guidelines. In the case of the existing cell 
lines, the cell lines that have been made, reported, we know 
all the details about how the tissues were obtained, I think it 
is going to be very straightforward. We have a legal opinion, 
we have the human embryo research panel guidance, we have 
regulations with regard to fetal tissue research that are very 
useful.
    I believe that in the course of the next couple of months a 
clear set of guidelines governing work on those cells can be 
generated. I have asked Dr. Shapiro, the chairman of the 
National Bioethics Advisory Commission, if they would attempt 
to give us some preliminary information about this specific 
issue in the course of their larger evaluation of embryo 
research in general.
    I hope we will have our guidelines out for public comment 
within a couple of months. There will be a 30-day public 
comment period. At that point we can begin to allow our 
investigators to use Federal funds.
    Senator Specter. You say a couple of months, to April 1, 
and a 30-day comment period, and then that brings us to May 1?
    Dr. Varmus. Now, I do not want to prejudge exactly how my 
advisory committee will do its work and I do not know exactly 
how they will segregate the different domains of research, 
because they may find that some things are very cut and dried 
and we can move very quickly and that other issues, for example 
what to do in response to another set of cell lines----
    Senator Specter. Dr. Varmus, we understand you have the 
problems and we are pressing on the date so we can figure out 
the time parameters and we know how to respond. We do not want 
to schedule the next hearing prematurely.
    My red light is on. Let me yield to Senator Harkin.
    Senator Harkin. I just wanted to just follow up on one 
thing. Getting back to the time frame on how things work out, 
when can we expect results? For 23 years I have served on 
committees in the House and the Senate that deal with the 
National Science Foundation and now NIH. It has been my 
experience through those years that when you are dealing in 
basic research--and this is sort of basic and applied; there is 
kind of a fuzzy boundary here on this one--that sometimes you 
put a time frame, but sometimes serendipitous things happen in 
science. But they will not happen unless you start moving down 
the pathway.
    So you can talk about 5 years or something, but you never 
know. Maybe in a year from now or something some scientist 
working someplace, something happens and you come up with 
something. That is why I think it is so important to move ahead 
aggressively in this because, like I say, you never know.
    I just wanted to make that point, that a lot of times in 
science things just happen like that.
    Dr. Varmus. Well, I appreciate being castigated for my 
conservative position. I am usually thought of as too 
impetuous, so I appreciate your comments, Senator.
    Senator Harkin. Thank you, Dr. Varmus.
    Senator Specter. We are going to ask you to stay with us, 
Dr. Varmus and Dr. Rabb.
    I had announced at the outset that there are caucuses at 10 
o'clock, at least a Republican caucus at 10 o'clock. Yours too?
    Senator Harkin. Yes.
    Senator Specter. Also with Senator Harkin, the caucus of 
the Democratic Senators.
    We are going to move now to panel two. We are going to 
conclude the hearing by 10 a.m. We have not gotten Dr. Rabb 
into the definitions, but we do have your very learned opinion, 
and if you would stand by for some dialog and questions and 
answers.

                  SUMMARY STATEMENT OF DR. ERIC MESLIN

    We would like to call now Dr. Eric Meslin and Mr. Richard 
Doerflinger. Dr. Meslin is the executive director of the 
National Bioethics Advisory Commission and received his 
bachelor of arts degree from York University, Toronto, M.A. and 
Ph.D., in bioethics and philosophy at the Kennedy Institute of 
Ethics at Georgetown University, and author of some 35 academic 
articles and book chapters and peer reviewed literature.
    We welcome you here, Dr. Meslin, and look forward to your 
testimony. As I say, the clocks are set at 5 minutes to leave 
maximum time for questions and answers.
    Dr. Meslin. Thank you very much, Senator, and good morning. 
Good morning to you, Senator Harkin.
    I was privileged to appear before your subcommittee on 
December 2nd to offer some brief remarks on the subject of 
human stem cells research. At that hearing, Mr. Chairman, I 
informed the subcommittee that in his November 20 letter to 
President Clinton the NBAC chair, Dr. Harold Shapiro, addressed 
only the immediate issue of the purported experiment involving 
the fusion of a cow egg and a human cell and that NBAC would 
devote a majority of its next meeting to the broader issues 
raised by President Clinton in his November 14 letter to the 
commission, namely that NBAC undertake a thorough review of the 
issues associated with human stem cells research, balancing all 
ethical and medical considerations.
    Just this past week NBAC met for the 26 time since being 
established by President Clinton. The commission devoted the 
entire day, January 19, to the topic of human stem cells 
research, hearing testimony from a number of leading 
scientists, bioethicists, theologians, legal scholars, and the 
public. The purpose of this meeting was to provide NBAC with a 
deeper understanding of the ethical, scientific, legal, medical 
and policy issues that are raised by this important area of 
research.
    While the commission did not reach any immediate 
conclusions at that meeting, nor were they expecting to, it may 
be helpful to describe the range of issues that were discussed 
and then to describe our timetable for completing this report 
since I understand how important it is to you.
    In our view, an understanding of the legal status regarding 
the use of Federal funds to conduct human stem cells research 
provides an important context for fully understanding the 
ethical issues. At our recent meeting we were very interested 
to learn of the Office of the General Counsel's--that the 
Office of the General Counsel has rendered an opinion regarding 
whether Federal funds may be used for research conducted with 
human pluripotent stem cells.
    We are planning to carefully review this opinion as quickly 
as possible since it provides one of the many pieces of 
valuable information we will rely on to fully address the 
bioethical issues involved in this area of research.
    In testimony before us, Mr. Chairman, we heard some 
compelling arguments in favor of permitting research on human 
stem cells, based principally on the very promising results of 
previous animal studies. Several beneficial uses of these cells 
are anticipated and you have heard those from Dr. Varmus 
already.
    It was also clear that a number of important scientific 
issues must be resolved before any actual therapies can be 
developed or tested in human beings. These include how to 
specifically direct stem cells to differentiate into specific 
types such as cardiac, muscle, or nerve cells, how to overcome 
the problem of immune rejection of such transplanted tissue, 
and other items.
    We also heard some words of caution and objection to all 
forms of research involving the human embryo, the human fetus, 
or the cells or tissues derived from these sources 
respectively. Some of these concerns related to the potential 
for complicity in the use of cells derived from spare or excess 
embryos. Other concerns related to more fundamental objections 
to the use of human fetal or embryonic material irrespective of 
their source or potential for benefit.
    Mr. Chairman, the focus of the NBAC effort is to develop 
sound public policy proposals based on appropriate scientific, 
medical, ethical, and legal considerations. In this respect, we 
hope to use the experiences from a number of former 
deliberative bodies. As with all NBAC reports, our 
deliberations, agendas, transcripts, and working papers will be 
available on our website.
    In reviewing a working draft outline of the report prepared 
by my staff, the commission at its meeting expressed a strong 
interest in developing a report that was focused on a set of 
answerable and timely questions, but that would also be able to 
anticipate certain issues. The specific issues our report will 
address are now being developed for NBAC's consideration, but 
they will likely focus on some of the following points:
    Is there an ethically relevant distinction between research 
using human stem cells derived from fetal material versus 
research using human stem cells obtained from existing embryos?
    How should considerations about the source of human stem 
cells be incorporated into the analysis?
    Is it ethically acceptable to produce new human embryos as 
a source of stem cells for research?
    Finally, what is the appropriate role of the Federal 
Government in overseeing research of this kind?
    NBAC would hope that one of the results of its 
deliberations on this topic would be to identify the bioethical 
issues that ought to be considered when supporting such 
research or developing guidelines for reviewing research in 
this area.
    Now let me say a word about our timetable. As you know, Mr. 
Chairman, NBAC is subject to the Federal Advisory Committee 
Act, which you helped cosponsor. This requires that we conduct 
all of our business in public and come to conclusions in 
public. This means that any commission decisions, be they 
interim conclusions or final recommendations, can only occur at 
NBAC meetings.
    We are committed to completing this report by June 1999 or 
thereabouts, so NBAC and its staff have mobilized to work as 
expeditiously as possible. Additional meetings have now been 
scheduled. In fact, we will be meeting next Tuesday and 
Wednesday, February 2 and 3, in Princeton, NJ, and monthly 
thereafter.

                           pREPARED STATEMENT

    I should note, however, that the commission is also 
preparing for the possibility of being able to provide to the 
President conclusions on certain issues within the next few 
months. We are keenly aware of NIH's interest in moving forward 
with human stem cell research and Dr. Shapiro has already 
indicated to Dr. Varmus separately that if NBACreaches any 
interim conclusions they will be shared with NIH and others 
after they are transmitted to the President. Naturally, Mr. 
Chairman, we will be pleased to provide you and your staff with 
an update on our work as it proceeds.
    I would be pleased to answer any questions you may have.
    Senator Specter. Thank you very much, Dr. Meslin.
    [The statement follows:]
              Prepared Statement of Eric M. Meslin, Ph.D.
    Good morning Mr. Chairman and members of the subcommittee, my name 
is Eric Meslin, I am Executive Director of the National Bioethics 
Advisory Commission.
    I was privileged to appear before your subcommittee on December 2, 
1998 to offer some brief remarks on the subject of human stem cell 
research. At that hearing, Mr. Chairman, I informed the subcommittee 
that in his November 20th letter to President Clinton, the NBAC Chair, 
Dr. Harold Shapiro, addressed only the immediate issue of the purported 
experiment involving the fusion of a cow egg and a human cell, and that 
NBAC would devote a majority of its next meeting to the broader issue 
raised by President Clinton in his November 14, 1998 letter to the 
Commission, namely that NBAC ``undertake a thorough review of the 
issues associated with . . . human stem cell research, balancing all 
ethical and medical considerations.''
    Just this past week NBAC met for the 26th time since being 
established by President Clinton. The Commission devoted the entire 
day, January 19, to the topic of human stem cell research, hearing 
testimony from a number of leading scientists, bioethicists, 
theologians, legal scholars, and the public. The purpose of this 
meeting was to provide NBAC with a deeper understanding of the ethical, 
scientific, legal, medical, and policy issues that are raised by this 
important area of research. While the Commission did not reach any 
immediate conclusions--nor were they expecting to--it may be helpful to 
describe the range of issues that were discussed, and then to describe 
our timetable for completing this report.
    In our view an understanding of the legal status regarding the use 
of federal funds to conduct human stem cell research provides an 
important context for fully understanding the ethical issues. At our 
recent meeting, NBAC was interested to learn that the Office of the 
General Counsel of the Department of Health and Human Services has 
rendered an opinion regarding whether federal funds may be used for 
research conducted with human pluripotent stem cells derived from 
embryos created by in vitro fertilization or from primordial germ cells 
isolated from the tissue of non-living fetuses. We are planning to 
carefully review this opinion since it provides one of the many pieces 
of valuable information we will rely on to fully address the bioethical 
issues involved in this area of research.
    In testimony before us, we heard some compelling arguments in favor 
of permitting research on human stem cells, based principally on the 
very promising results of previous animal studies. Several beneficial 
uses of these cells are anticipated, including: understanding basic and 
developmental biology; the development of transplantation therapies for 
the treatment of diseases such as Parkinson's disease and diabetes; the 
discovery of new drugs; and the study of infertility and birth defects.
    It was also clear that a number of important scientific issues must 
be resolved before any actual therapies can be developed or tested in 
human beings. These issues include: how to specifically direct stem 
cells to differentiate into specific types, such as cardiac muscle or 
nerve cells; how to overcome the problem of immune rejection of such 
transplanted tissue; and how stem cells derived from fetal primordial 
germ cells (KG cells) differ from stem cells derived from embryonic 
sources (ES cells), and whether these differences have any functional 
importance.
    We also heard some words of caution, and objection to all forms of 
research involving the human embryo, the human fetus, or the cells or 
tissues derived from these sources respectively. Some of these concerns 
related to the potential for complicity in the use of cells derived 
from spare or ``excess'' embryos. Other concerns related to more 
fundamental objections to the use of human fetal or embryonic material, 
irrespective of their source or potential for benefit.
    The focus of the NBAC effort is to develop sound public policy 
proposals based on appropriate scientific, medical, ethical, and legal 
considerations. In this respect, we hope to use the experiences from 
former deliberative bodies including the National Commission for the 
Protection of Human Subjects of Biomedical and Behavioral Research, the 
DHHS Ethics Advisory Board, the Fetal Tissue Transplantation Research 
Panel, and the NIH Director's Embryo Research Panel. We will also be 
contacting a variety of public, professional, scientific and other 
organizations seeking their views on these issues. And, as with all 
NBAC reports, our deliberations, agendas, transcripts and working 
papers will be available on our website at www.bioethics.gov.
    In reviewing a working draft outline of the report prepared by my 
staff, the Commission expressed an interest in developing a report that 
was focused on a set of answerable and timely questions, but that would 
also be able to anticipate certain issues. The specific issues our 
report will address are now being developed for NBAC's consideration, 
but they will likely focus on some of the following points:
  --Is there an ethically relevant distinction between research using 
        human stem cells derived from fetal material vs. research using 
        human stem cells obtained from existing embryos?
  --How should considerations about the source of human stem cells be 
        incorporated into the analysis?
  --Is it ethically acceptable to produce new human embryos as a source 
        of stem cells for research?
  --What is the appropriate role of the federal government in 
        overseeing research of this kind?
    NBAC would hope that one of the results of its deliberations on 
this topic would be to identify the bioethical issues that ought to be 
considered when supporting such research, or developing guidelines for 
reviewing research in this area.
    Now let me say a word about our timetable. As you know, Mr. 
Chairman, NBAC is subject to Federal Advisory Committee Act (1972) 
which requires that we conduct all of our business in public, and come 
to conclusions in public. This means that any Commission decisions--be 
they interim conclusions or final recommendations--can only occur at 
NBAC meetings. We are committed to completing this report by June 1999, 
or thereabouts, so NBAC and it staff have mobilized to work as 
expeditiously as possible. Additional meetings have been scheduled--we 
will be meeting next week, February 2-3, in Princeton, New Jersey, and 
monthly thereafter. I should note, however, that the Commission is 
preparing for the possibility of being able to provide to the President 
conclusions on certain issues within the next few months. We are aware 
of NIH's interest in moving forward with human stem cell research, and 
Dr. Shapiro has indicated to Dr. Varmus that if NBAC reaches any 
interim conclusions they will be shared with NIH and others after they 
are transmitted to the President. Naturally, Mr. Chairman, we will be 
pleased to provide you and your staff with an update on our work as it 
proceeds.
    I would now be pleased to answer any questions you may have.

              SUMMARY STATEMENT OF RICHARD M. DOERFLINGER

    Senator Specter. We now turn to Mr. Richard Doerflinger, 
associate director for policy development at the Secretariat 
for Pro-Life Activities, National Conference of Catholic 
Bishops. Welcome, Mr. Doerflinger. We appreciate your coming 
back, and the floor is yours.
    Mr. Doerflinger. Thank you, Mr. Chairman.
    I want to begin by noting that a point I made in my 
December 2d testimony on this same matter has received new 
support from recent events. Since then two startling scientific 
breakthroughs have made it even more clear that destructive 
embryo research is unnecessary. Advances in the use of 
telomerase to promote regeneration of human tissues and the new 
discovery that adult stem cells may be far more versatile than 
was once thought offer the promise that embryonic stem cells 
may simply be irrelevant to future medical progress.
    At the December 2d hearing Dr. Varmus noted that, while 
adult stem cells can be obtained from bone marrow, cord blood, 
and so on, they are of limited use compared to embryonic cells 
because they cannot form other kinds of tissues such as nerve 
and skin. The most recent issue of ``Science'' suggests that 
this judgment may well have been premature, that in fact stem 
cells at a later stage of development can cross over these 
boundaries and be adapted to perform the use of any different 
kind of cell.
    This subcommittee has now held three hearings on one narrow 
avenue of research, precisely the avenue that raises the most 
obvious moral and legal problems, so far to the exclusion of 
all other alternatives, even when those avenues may be more 
promising. The use of adult stem cells, for example, is said to 
promise the complete avoidance of the tissue rejection problems 
that Dr. Varmus has noted still need to be solved using 
embryonic cells.
    I would urge the subcommittee to expand its vision, to 
explore the alternatives that will advance medical progress and 
the wellbeing of patients without demeaning human dignity.
    Turning now to the legal memorandum prepared by the 
Department of Health and Human Services, in its effort to find 
that Federal funding of embryonic stem cell research is 
consistent with Congressional intent HHS has overlooked some 
rather obvious facts and created its own arbitrary definition 
of a human embryo and, even more striking, of a human being 
that have no basis in biology or Federal law.
    First looking at current laws on embryo and live fetal 
research. HHS now claims that current law on embryo research 
does not pose a barrier to embryonic stem cells research 
because the law protects only the embryo, which is an organism, 
and a stem cell, obtained by destroying embryos, is not an 
organism. HHS even cites me on this point.
    But they ignore other parts of my testimony and, more 
importantly, ignore two important aspects of current law. 
First, as I noted on December 2nd, there is a factual 
uncertainty as to exactly what happens to the stem cells that 
Dr. Gearhart of Johns Hopkins University has cultured from 
fetal germ cells after abortions.
    After being cultured, some of these stem cells have a 
tendency to come back together and show signs of developing as 
an early embryo. Whether the formation of early embryos does 
take place in such a culture and whether that can be prevented 
by adapting the research is a scientific question, cannot be 
answered by attorneys. A stem cell is not an organism, but the 
possibility must be explored that groups of stem cells may 
recongregate in some of this research to form an entity that 
is, however briefly, a living organism, in which case this 
research could not be funded.
    HHS seeks to avoid this factual inquiry by inventing its 
own narrower definition of an embryo, which is not found in 
Federal law. Such an entity, HHS argues, cannot be an embryo 
because, even if implanted in a womb, it could not become a 
``human being.'' Oddly enough, the key phrase ``human being'' 
is not defined, but from the context it seems to refer to a 
live-born infant. In Dr. Varmus' testimony, I noted he said a 
human being is a mature organism. So I am beginning to wonder 
whether my 6 year old son qualifies.
    Embryology textbooks, however, tell us that in biological 
terms to embryo is a human being, and the current Federal law 
treats the embryo as a human subject. Since 1975, it has 
treated the human embryo as a human subject, to be protected 
from harmful research from implantation onwards, and the 
current embryo research rider is intended to extend that 
protection back before implantation, to the embryo in the 
laboratory.
    Second, HHS seems to misread the embryo research rider 
itself rather obviously by saying that this research can be 
funded as long as Federal funds are not used for the actual 
destruction of the embryo. They can be used for all subsequent 
work with the stem cells so derived.
    But Congress knows how to write a rider that says you 
simply cannot use Federal funds for that act. It wrote the 
rider that way when it dealt with creation of human embryos. It 
said Federal funds cannot be used for creation of embryos. Then 
it said Federal funds cannot be used for research in which a 
human embryo or embryos are destroyed or discarded or subjected 
to risk of harm. Obviously, that means if this is an integral 
part of the research protocol, even if it is not directly 
funded by Federal funds, the destructive harvesting of embryos 
is not supposed to be something that is part of a research 
project funded by Congress.
    Finally, HHS ignores the possibility that the fetal tissue 
transplantation guidelines now in law apply also to the 
destruction of embryos in the laboratory. The statute clearly 
says that it covers tissue derived from embryos or fetuses, and 
it only allows the use of that tissue if the subject was dead 
before the tissue was obtained and only if the destruction was 
not altered in its method or timing by the needs of the 
research.
    Well, in all of the research in which embryos are destroyed 
here, the destructive process is geared exactly toward 
obtaining usable research tissue and toward nothing else. When 
embryos are discarded in an IVF clinic, they do not use 
immunosurgery to dissect the inner cell mass from the 
trocoblast. They simply throw them away. Everything about the 
harvesting procedure is altered to obtain usable tissue, and it 
is the harvesting procedure that is itself the abortion or the 
destruction.

                           PREPARED STATEMENT

    In conclusion, if Congress wishes to insulate its funding 
of medical advances from the destruction of innocent life, 
there is a very simple way to do just that. It should devote 
its funds to stem cells techniques and other promising avenues 
of research that in no way depend upon such destruction. In 
that way our government will truly serve all the people by 
showing that it will not promote the destruction of one human 
being to serve another or the development of treatments that 
millions of Americans would find it morally abhorrent to use.
    Thank you.
    [The statement follows:]
              Prepared Statement of Richard M. Doerflinger
    I am Richard M. Doerflinger, Associate Director for Policy 
Development at the Secretariat for Pro-Life Activities, National 
Conference of Catholic Bishops. I am grateful for the opportunity to 
present the Catholic bishops' concerns about efforts to justify the use 
of cells from deliberately destroyed human embryos in federally funded 
research.
    I must begin by noting that a point I raised in my December 2 
testimony before this subcommittee has received new support from recent 
events. I said then that the goals some wish to serve by killing human 
embryos for their stem cells can be achieved in other, morally 
acceptable ways. Even at that time, one of the advances cited by 
supporters as a future benefit of embryo research--the ability to grow 
new blood vessels in the heart--was already in clinical use in human 
patients with no need for embryonic cells.\1\ In the six weeks that 
have elapsed since then, however, two startling scientific 
breakthroughs have made it even more clear that destructive embryo 
research is unnecessary. The use of telomerase to promote regeneration 
of human tissues,\2\ and the new discovery that adult stem cells may be 
far more versatile than was once thought,\3\ offer the promise that 
embryonic stem cells may simply be irrelevant to future medical 
progress.
---------------------------------------------------------------------------
    \1\ See: ``Technique grows new heart vessels,'' MSNBC Health, 11/9/
98; ``Injected Genes Help Grow Heart Bypasses,'' Washington Post, 11/
10/98, A3.
    \2\ C, Morales et al., ``Absence of cancer-associated changes in 
human fibroblasts immortalized with telomerase,'' 21 Nature Genetics 
115-8 (January 1999); see comments in Ruth Larson, ``Scientists find 
new life for old cells,'' Washington Times, 12/29/98, Al.
    \3\ C. Bjornson et al., ``Turning Brain into Blood: A Hematopoietic 
Fate Adopted by Adult Neural Stem Cells in Vivo,'' 283 Science 534-7 
(22 January 1999). See comments in: Evelyn Strauss, ``Brain Stem Cells 
Show Their Potential,'' 283 Science 471 (22 January 1999); Paul Recer, 
``Patient's Cells May Grow New Organs,'' Associated Press, 1/21/99 
(``If such a technique also worked in humans, embryos may not be needed 
for such research''); Nicholas Wade, ``Cell Experiment Offers Hope for 
Tissue Repair,'' New York Times, 1/22/99, A21 (the technique avoids the 
``ethical considerations'' arising from embryonic cells, as well as the 
``immune rejection problems'' they can pose); Lee Bowman, `` `Master 
cells' offer repair kits,'' Washington Times, 1/22/99, A9 (``it could 
mean that stem cells don't have to come from embryos to generate 
specialized cells'').
---------------------------------------------------------------------------
    At the December 2 hearing, responding to our proposed list of 
promising alternatives to embryonic stem cell research, National 
Institutes of Health director Harold Varmus said that while adult stem 
cells can be obtained from bone marrow, cord blood and so on, they are 
of limited use because they cannot form other kinds of tissue such as 
nerve and skin. The most recent issue of Science suggests that this 
judgment was premature.
    This subcommittee has now held three hearings on one narrow avenue 
of research--precisely the avenue that creates the most obvious moral 
and legal problems--to the exclusion of all other alternatives, even 
when those avenues may be more promising. I urge the subcommittee to 
expand its vision, to explore the alternatives that will advance 
medical progress and the well-being of patients without demeaning human 
dignity.
    I would like to turn now to the legal memorandum prepared by the 
General Counsel of the Department of Health and Human Services (``HHS 
memo''). In its effort to find that federal funding of embryonic stem 
cell research is consistent with congressional intent, HHS has 
overlooked some obvious facts, and created its own arbitrary definition 
of a human embryo that has no basis in biology or federal law.
    Specifically, the HHS memo ignores key aspects of the current 
appropriations rider on embryo research (Section 511 of the Labor/HHS 
appropriations bill for fiscal year 1999), statutory and regulatory 
provisions on live fetal research (42 U.S.C. Sec. 289g; 45 CFR 
Sec. 46.201 ff.), and statutory law on fetal tissue transplantation 
research (42 U.S.C. Sec. 289g-1).
Laws on Embryo Research and Live Fetal Research
    HHS claims that current law on embryo research does not cover 
embryonic stem cell research, because the law protects only the embryo, 
which is an ``organism''--and a stem cell obtained by destroying an 
embryo is not an ``organism.'' HHS even cites my December 2 testimony 
for the proposition that a stem cell is not an organism--but the 
authors overlook other parts of my testimony. More importantly, they 
ignore two important aspects of current law.
    (1) Distorted definitions of ``embryo'' and ``human being.''--
First, as I noted on December 2, there is some uncertainty about the 
status of the cells that Dr. Gearhart of Johns Hopkins University has 
cultured from fetal germ cells after abortions. After being cultured, 
some of these stem cells may have a tendency to come back together and 
develop as an early embryo.\4\ Whether the formation of early embryos 
takes place in such a stem cell culture, and whether it can be 
prevented, is a scientific question. It demands a scientific answer, 
before federal funds are spent on the research--because these funds by 
law cannot be used, even inadvertently, to create embryos which briefly 
develop and then die in culture. In other words, a stem cell is not an 
organism--but the possibility must be explored that groups of stem 
cells may recongregate to form an entity that is, however briefly, a 
living organism.
---------------------------------------------------------------------------
    \4\ In Dr. Gearhart's experiment, ``embryoid bodies'' had formed 
``complex structures'' in culture ``closely resembling an embryo during 
early development''; these structures ``appear to recapitulate the 
normal developmental processes of early embryonic stages and promote 
the cell-cell interaction required for cell differentiation.'' M. 
Shamblott et al., ``Derivation of pluripotent stem cells from cultured 
human primordial germ cells,'' 95 Proceedings of the National Academy 
of Sciences 13726-13731 (November 1998) at 13726, 13729. These remarks 
were cited in my December 2 testimony, at note 13.
---------------------------------------------------------------------------
    HHS seeks to avoid this factual inquiry by inventing its own 
definition of an ``embryo''--a definition with no basis in science or 
law. Such an entity, HHS argues, could not be an embryo because, even 
if implanted in a womb, it could not become a ``human being.'' The 
phrase ``human being'' is left undefined, but from the context it seems 
to refer solely to a liveborn infant.
    Is ``human being'' intended here as a scientific term? Clearly not, 
since embryology textbooks tell us that in biological terms, the embryo 
is a human being.\5\ Even the NIH's Human Embryo Research Panel, whose 
recommendations for federal funding of embryo experiments were found 
morally unacceptable by President Clinton and Congress, called the 
early embryo ``a developing form of human life.''\6\
---------------------------------------------------------------------------
    \5\ See: Keith Moore and T.V.N. Persaud, The Developing Human: 
Clinically Oriented Embryology (W.B. Saunders 1998)(6th edition), p. 2 
(``A zygote is the beginning of a new human being''); T.W. Sadler, 
Langman's Medical Embryology (Williams and Wilkins 1995)(7th edition), 
p. 3 (``The development of a human being begins with fertilization''); 
William J. Larsen, Human Embryology (Churchill Livingstone 1997)(2nd 
edition), p. 1 (``the male and female sex cells or gametes . . . will 
unite at fertilization to initiate the embryonic development of a new 
individual'').
    \6\ National Institutes of Health, Report of the Human Embryo 
Research Panel (November 1994), 2.
---------------------------------------------------------------------------
    Is it, then, a legal term? No, since the phrase ``human being'' is 
not used in this part of federal law. Instead, since 1975, federal 
regulations have defined the human embryo, from implantation in the 
womb onward, as a ``human subject'' to be protected from harmful 
experiments, regardless of whether it is expected to survive to live 
birth.\7\ Current law on fetal research explicitly demands that a fetus 
to be aborted have the same protection as the fetus intended for live 
birth (42 U.S.C. Sec. 289g(b)).
---------------------------------------------------------------------------
    \7\ ``Human subject,'' in turn, is defined as a ``living 
individual'' subjected to research (45 CFR Sec. 46.102(f)); Subpart B 
of Part 46 provides special protections for fetuses as human subjects. 
``Fetus'' includes ``the product of conception from the time of 
implantation'' (45 CFR Sec. 46.203(c)). Through appropriations riders, 
Congress since 1995 has extended this same protection to all human 
embryos not previously protected as human subjects.
---------------------------------------------------------------------------
    Moreover, federal law on fetal tissue refers to the use of tissue 
from embryos and fetuses after a ``spontaneous or induced abortion'' or 
a stillbirth (42 U.S.C. Sec. 289g-1(g)). The HHS memo's definition 
would make this provision self-contradictory: A fetus that has 
spontaneously aborted did not have the ability to become what HHS calls 
a ``human being,'' and so (by the HHS approach) cannot be called an 
``embryo'' or ``fetus'' at all.
    The current appropriations rider on embryo research is crystal 
clear. To determine whether an entity is an ``embryo'' we need only 
determine whether it is a living organism here and now (Section 511 
(b)). Section 511 says nothing about restricting this term to embryos 
that can be shown to have the ``potential to develop'' to live birth. 
In any case, testing an embryo's ability to become a born ``human 
being'' is clearly impossible once one has used such a definition to 
justify destroying that embryo in the laboratory.
    HHS's strange and arbitrary digression on the phrase ``human 
being'' does not serve the goal of understanding federal law, but the 
very different goal of justifying harmful experiments. Some researchers 
have actually offered to engineer lethal defects in advance into the 
embryos they create and destroy with federal funds--so that one could 
argue that these embryos would never become ``human beings'' and so are 
exempt from current law.\8\
---------------------------------------------------------------------------
    \8\ ``The goal is to create a developing mass of mostly human cells 
that's crippled enough to prevent its development into a person, yet 
healthy enough during the first week of existence to produce the 
crucial `stem cells' that scientists want to collect.'' Rick Weiss, 
``Can Scientists Bypass Stem Cells' Moral Minefield?'', Washington 
Post, 12/14/98, A3.
---------------------------------------------------------------------------
    Moreover, at this subcommittee's January 12 hearing, the theory was 
offered that unwanted or frozen embryos from fertility clinics can 
ethically be used for destructive research, because in any case they 
would not have produced a ``human life.'' This did not refer to any 
defect in the embryos, but simply to the fact that parents have chosen 
not to let them survive. Such an approach makes a mockery of the 
current law, which was intended to protect such ``spare'' embryos from 
being harmed by the federal government regardless of what harm may be 
intended by others in the private sector. HHS would reduce current laws 
against harmful experiments on prenatal human life to this: Whenever 
someone wants to discard or destroy human embryos or fetuses instead of 
allowing them to survive, that very choice excludes them from the scope 
of the law's protection. Prenatal human beings would be protected by 
federal regulations only when they are in no need of such protection.
    (2) Misreading the embryo research rider.--HHS's second error 
arises from a misreading of the appropriations rider. The HHS memo 
narrows its focus to the question whether a stem cell is an embryo, as 
though what had to be done to an embryo to obtain the stem cell is 
irrelevant. The implication here is that, so long as federal funds are 
not used for the specific act of destroying a human embryo, such funds 
may be used for all subsequent research on the resulting cells and 
tissues. But this contradicts the plain words of the appropriations 
rider. It does indeed ban the use of federal funds for ``the creation 
of a human embryo or embryos for research purposes'' (apparently 
leaving open the possibility that federal funds might be used to do 
life-saving or therapeutic research on an embryo that was already 
created without federal funds) (Sec. 511(a)(1)). But the provision goes 
on to say that federal funds may not be used for ``research in which a 
human embryo or embryos are destroyed, discarded, or knowingly 
subjected to risk of injury or death . . .'' (Sec. 511(a)(2)). Clearly, 
if Congress wished to say merely that federal funds may not be used for 
destroying and discarding embryos, it knew how to say that; instead it 
used this broader phrase that is not used in the parallel clause on 
creating embryos.
    How do we interpret the phrase ``research in which?'' A reasonable 
reading is that federal funds may not be used for research for the 
purpose of which human embryos were harmed or destroyed. Or, that 
federal funds may not be used for research that cannot be done without 
the prior harming or destroying of human embryos; or that such funds 
may not be used for research if such destruction is part of the 
researcher's protocol.\9\ Only one interpretation is impossible, 
because Congress went out of its way to exclude it--the interpretation 
that this rider bans only the direct use of federal funds for the 
destructive harvesting of cells itself. That impossible interpretation 
is the one that HHS seems to accept.
---------------------------------------------------------------------------
    \9\ By these interpretations, both Dr. West's experiment (relying 
on the destructive harvesting of cells from embryos created by somatic 
cell nuclear transfer [cloning]) and Dr. Thomson's (relying on 
destructive harvesting of cells from ``spare'' embryos from fertility 
clinics) are barred from receiving federal funds. A mere bookkeeping 
distinction between funds used to destroy the embryo and funds used to 
work with the resultant cells is not sufficient.
---------------------------------------------------------------------------
Current Law on Fetal Tissue Research
    HHS notes that ``some'' of the proposed research may implicate 
current law on fetal tissue research, citing Dr. Gearhart's experiment 
using fetal tissue from abortions as an example. Hinted at, but not 
explored by HHS, is the possibility that other proposed experiments--
those relying on the destruction of human embryos in the laboratory--
may also be governed by these provisions.
    In fact, the law explicitly covers tissue obtained from a ``human 
embryo or fetus'' (42 USC Sec. 289g-1(g)). And since ``fetus'' is 
defined in this area of law to include any product of conception from 
implantation in the womb onward, the separate word ``embryo'' here can 
only refer to the unimplanted embryo--the embryo in the laboratory. In 
that case, the word ``abortion'' in this provision should be construed 
to include the direct destruction of an embryo in the laboratory--for 
otherwise the word ``embryo'' in the law would have no application 
whatever.
    If this interpretation is correct--if the use of tissue harvested 
from embryos in the laboratory is governed by current guidelines on 
fetal tissue research--then such tissue cannot be used for federally 
funded tissue transplantation research. For such use would violate the 
guideline demanding that the ``timing, method or procedures'' for the 
abortion must not be altered ``solely for the purposes of obtaining the 
tissue'' for a federal research project (42 U.S.C. Sec. 289g-
1(b)(2)(A)(ii)). Clearly, the destructive method used to obtain stem 
cells from these embryos--the use of immunosurgery to extract the inner 
cells--is never used to discard ``spare'' embryos in fertility clinics, 
but is employed solely to obtain usable tissue for research.\10\
---------------------------------------------------------------------------
    \10\ Among the inadequacies in current compromise provisions on 
fetal tissue is the inclusion of the word ``solely'' here. It does not 
adversely affect the issue at hand, but could be used to justify 
federal collaboration with practitioners of the grotesque partial-birth 
abortion technique to obtain brain tissue for research purposes. Since 
the technique already involves killing a partly born child by 
suctioning out his or her brain tissue before completing delivery, it 
need not be altered ``solely'' to obtain usable tissue. Congress has 
repeatedly voted to make partial-birth abortion a federal crime, so 
presumably did not intend to state a preference for this procedure as a 
source of material for federally funded research.
---------------------------------------------------------------------------
    To be sure, this guideline's meaning is somewhat unclear, because 
it refers to influencing the timing and method for ``terminat[ing] the 
pregnancy.'' Ordinarily such a phrase would not be used to describe the 
destruction of an embryo in the laboratory. However, one must recall 
what Congress was trying to prevent by enacting this provision. Members 
had learned of a procedure in Sweden, for example, in which the unborn 
child intended for abortion was killed by suctioning out its brain 
tissue for research on Parkinson's disease, and only afterward expelled 
from the womb.\11\ Here, the harvesting procedure was itself the 
``abortion,'' in the sense that it caused the death of the unborn 
child. Such abuses were to be prevented in federally funded research in 
the United States by this ban on altering the timing and method of 
abortion. The destructive harvesting of stem cells to cause an embryo's 
death, before it is discarded by a researcher or fertility clinic, 
provides a very close analogy to such abuses which Congress sought to 
prevent.
---------------------------------------------------------------------------
    \11\ O. Lindvall et al., ``Human Fetal Dopamine Neurons Grafted 
Into the Striatum in Two Patients With Severe Parkinson's Disease,'' 46 
Archives of Neurology 615, 616 (June 1989).
---------------------------------------------------------------------------
    Indeed, this law clearly was intended to permit only the use of 
tissue that had been ``obtained from a dead embryo or fetus''--one that 
died of other causes before tissue was harvested (42 USC Sec. 289g-
1(g)). Even in such cases, the guidelines were intended to prevent any 
influence by researchers upon the decision to abort. The idea of using 
tissue harvested in a way that itself destroys the embryo or fetus was 
not proposed by any member of Congress.\12\
---------------------------------------------------------------------------
    \12\ The provision's chief sponsor said: ``This issue . . . is not 
about abortion . . . This is about what happens after an abortion takes 
place: Will the tissue be discarded or will the tissue be used for 
research . . . ?'' (Rep. Waxman, Cong Record, 3/10/93, H1131; emphasis 
added). Harvesting of embryonic stem cells is not done after the embryo 
is killed; it is precisely what kills the embryo.
---------------------------------------------------------------------------
Conclusion
    In short, there is no clear support in any relevant provision of 
federal law and regulations for the HHS opinion on using stem cells 
from deliberately destroyed human embryos--in fact, one can find much 
that is contrary to that opinion. The HHS memo ignores the explicit 
language of the current appropriations rider on embryo research; 
creates its own arbitrary and unsupported approach to defining a 
``human being''; and overlooks the possible relevance of current law on 
fetal tissue to the destructive harvesting of cells from human embryos.
    In a broader view, it seems clear that all these laws and 
regulations enacted over the past 24 years were intended to ensure that 
the federal government never encourages the destruction of prenatal 
life as a source for research material. The HHS opinion would 
eviscerate this longstanding policy. Researchers who destroy human 
embryos would receive direct federal rewards for such destruction, 
since their lethal harvesting of tissue would make them uniquely 
eligible for federal grants for research on embryonic stem cells. The 
fact that such economic incentives would reward such destruction after 
the fact, instead of being bestowed in advance to pay directly for such 
destructive harvesting, is of no great significance.
    If Congress wishes to insulate its funding of medical advances from 
the destruction of innocent life, there is a simple way to do just 
that. It should devote its funds to stem cell techniques and other 
promising avenues of research that in no way depend upon such killing. 
In that way our government will truly serve all the people, by showing 
that it will not promote the killing of one human being to serve 
another, or the development of treatments that millions of Americans 
would find it morally abhorrent to use.
    (Attachments: Reports of recent developments in alternatives to 
embryonic stem cell research)
                                 ______
                                 

              [From the Washington Post, January 21, 1999]

                  Patient's Cells May Grow New Organs
                            (By Paul Recer)
    A patient's own cells might someday be used to grow new organs--a 
development suggested by a breakthrough lab experiment that found the 
building-block cells that normally make brain tissue in adult mice 
could be changed into blood-making cells.
    These so-called stem cells, the foundation source of the body's 
tissue, have been identified as a way to make new skin, liver and other 
organs. But in previous research the cells were harvested from embryos, 
a technique that set off a storm of ethical objections.
    The new research suggests that even mature stem cells, such as from 
the adult brain or bone marrow, can change into the progenitor cells 
for other types of tissue. If such a technique also worked in humans, 
embryos may not be needed for such research.
    ``You may be able to use your own stem cells to make new tissue,'' 
said Angelo L. Vescovi, head of a team that conducted the mouse 
experiment. ``As a concept, I don't see any problem in adult stem cells 
being used to make new skin, for instance.''
    The research shows ``there are alternative strategies'' to 
harvesting stem cells from embryos, said Dr. Ronald McKay, a National 
Institutes of Health researcher and a pioneer in stem cell studies.
    Stem cells are the mortar and brick for growing all of the body's 
tissues. In a developing embryo, they produce the cells that become the 
body parts. After birth, some stem cells are specially programmed to 
replenish some tissues such as blood and skin.
    Researchers earlier had isolated stem cells from human embryos or 
from aborted fetuses, and grew the cells in a lab. When treated with 
specific proteins, the cells began to grow different types of tissue 
cells.
    That work set off a frenzy of studies. But the research was 
shadowed by ethical concerns because it was thought that only stem 
cells from embryos retained the ability to grow into a variety of 
organs. Many groups objected to medical experimentation with human 
embryos and Congress forbade federal money for such studies.
    It also led President Clinton to order his National Bioethics 
Advisory Commission to consider the moral issues of such research. 
Earlier this week, NIH director Harold Varmus said his agency concluded 
that research with lab-grown stem cells didn't violate the 
congressional mandate, even though the cells originated from human 
embryos.
    But Vescovi's work with mice suggests that any stem cell even from 
an adult can be reeducated to make any type of tissue.
    Vescovi, of the National Neurological Institute in Milan, Italy, is 
senior author of a study to be published Friday in the journal Science.
    ``This shows that the mature stem cells are a lot more plastic than 
we imagined . . . they can produce a lot more cell types than was 
previously thought,'' said Christopher Bjornson, a researcher at the 
University of Washington, Seattle, on the team.
    ``A bone marrow stem cell might be able to produce tissue for the 
brain . . . and the skin stem cell might be able to make other cell 
types,'' Bjornson said.
    In the experiment, researchers used mouse neural stem cells, which 
normally would develop into three types of brain and nerve tissue.
    They injected the cells into the blood stream of a second group of 
mice whose bone marrow had been killed with radiation. The cells 
migrated naturally to the void left by the killed bone marrow.
    Once there, they transformed from neural stem cells into blood-
making cells a complete change from their original role.
    But just what caused the change is unknown.
    And it's unclear if adult neural stem cells have been isolated in 
humans, although mature stem cells for intestines, skin and blood have 
been identified, Vescovi said. McKay said his lab and one other had 
found mature human neural stem cells.
    Bjornson emphasized that the new work involves only mice and that 
``huge steps are needed'' before stem cell technology can ever be used 
for humans.
    One key problem is learning how to direct stem cells to grow a 
specific organ. Although researchers at Johns Hopkins University and 
the University of Wisconsin, Madison, had earlier prompted stem cells 
to start making a variety of tissue cells, the growth was not guided 
toward a specific cell type.
    If that problem can be solved, researchers believe it's 
theoretically possible that stem cells could be used to grow new livers 
or skin, make cells to renew a failing heart, or replace nerve cells 
killed by Alzheimer's.
                                 ______
                                 

             [From the Washington Times, January 22, 1999]

   ``Master Cells'' Offer Repair Kits; Study Suggests They Could be 
                      Transplanted to Form Tissue
                            (By Lee Bowman)
    A new study suggests that adult ``master cells'' can be 
transplanted to form a number of types of tissue, a capability that 
could mean humans carry their own built-in tissue repair kits.
    Until now, scientists have only been able to experimentally use 
immature stem cells cultivated from embryos and aborted fetuses for 
such transplants.
    But if the study reported today in the journal Science can be 
confirmed and expanded to humans, it could mean that stem cells don't 
have to come from embryos to generate specialized cells. Instead, they 
can be moved around between different organ systems within the body.
    A team led by Angelo Vescovi of NeuroSpheres Ltd. of Calgary, 
Alberta, and the National Neurological Institute of Italy used neural 
stem cells from the central nervous systems of mice in a transplant 
that allowed them to assume the job of bone marrow ``master cells'' 
that produce the different varieties of blood cells in a second group 
of mice.
    ``If they behave similarly to their mouse counterparts, human 
neural stem cells may provide a renewable source of cells that could be 
used in blood system reconstitution in various blood diseases and 
disorders,'' and potentially other diseases, Mr. Vescovi said.
    Normally, the neural stem cells generate replacements for the major 
cells found in the adult brain, neurons and their support cells. Mr. 
Vescovi and his colleagues took some of these cells from one group of 
mice, genetically labeled them and injected them into the bloodstream 
of a second group of rodents whose bone marrow had been destroyed by a 
nearly fatal dose of radiation.
    Once in the blood stream, the neural cells seeded the mice's bone 
marrow and spleen, another point for blood production, and took over 
the job of the destroyed blood stem cells within two weeks and produced 
a range of blood cells and important immune-system cells within 20 to 
22 weeks.
    ``It took us a while to believe our own data. The tissue of the 
body has always been seen as unchangeable,'' Mr. Vescovi said.
    As a comparison, researchers injected another group of irradiated 
mice with donated blood system stem cells from mice. They, too, took 
over the job of the stem cells that had been destroyed, but produced 
blood cells an average of three weeks faster than did the transplanted 
brain cells.
    ``This extra time required suggests that the neural stem cells 
undergo additional steps of fate determination, differentiation and 
maturation than do the blood stem cells'' to take over the same job, 
Mr. Vescovi said.
    But that they do eventually adapt themselves to work in a new 
system means that adult stem cells are still versatile and not 
genetically predestined to work only with the brain, blood, skin or 
intestines, for instance.
    The promise of embryonic stem cells has been that they have the 
potential to become any type of tissue within the body as long as they 
are given the proper genetic signals. Scientists haven't yet figured 
out how to turn that switch by inserting some or all of the DNA from 
the cells that they want to replicate, but it had been assumed that 
stem cells from adults were already too set in their ways to assume new 
tasks.
    The new study suggests that reactivating dormant genetic coding in 
stem cells may not require DNA transfers.
                                 ______
                                 

             [From the Washington Times, December 29, 1998]

                 Scientists Find New Life For Old Cells
      rejuvenated tissue could aid burn victims, fend off wrinkles
                            (By Ruth Larson)
    Aging without wrinkles? It could become a reality with a new 
technique for ``immortalizing'' human cells, Texas researchers say.
    Lab cultures of human cells injected with an anti-aging enzyme have 
lived four times longer than their normal lifetimes. More importantly, 
they have shown no sign of developing cancer, as some researchers had 
feared.
    ``At long last we've learned how to put cellular aging on hold,'' 
said Jerry Shay, professor of cell biology and neuroscience at the 
University of Texas Southwestern Medical Center in Dallas. His research 
will be published today in the journal Nature Genetics.
    Introducing an enzyme called ``telomerase'' into the cells 
effectively resets their biological clocks, enabling them to live and 
divide like young, vigorous cells.
    ``This doesn't mean that we're going to be able to get a whiff of 
telomerase and then live forever,'' Mr. Shay cautioned. ``We're still 
going to die, because this won't solve all our problems. There will 
still be car accidents and shootings,'' and health problems unrelated 
to cellular aging.
    Still, the ability to rejuvenate specific cells in the body opens 
up a dazzling array of possibilities. Doctors could grow skin grafts 
for burn victims using their own skin, insulin-producing cells for 
diabetics, or muscle tissue for sufferers of muscular dystrophy. And 
yes, they might even help combat wrinkles.
    ``Women--and some men--spend lots of money to get rid of 
wrinkles,'' Mr. Shay said in a telephone interview. As individuals age, 
their skin cells produce less of the connective tissue collagen, so the 
skin becomes thinner, less elastic and more susceptible to wrinkles.
    ``Someday it might be possible to take one of a lady's skin cells, 
inject it with telomerase, and rejuvenate her skin so she can make her 
own collagen again,'' he said. ``It's speculative right now, but it's a 
very real possibility in the future.''
    The biotech firm Geron Corp., based in Menlo Park, Calif., has been 
granted the right to commercialize the technique. Geron researchers 
have implanted telomerase-treated human cells into mice, to see if they 
would form tumors in the animals. They did not.
    ``Even though they were immortalized, these cells behaved just like 
normal cells,'' said Calvin Harley, Geron's chief scientific officer. 
The cells responded to normal growth regulators that prevent runaway 
cell growth.
    Geron is looking into several possible gene therapy applications, 
but Mr. Harley stressed that human applications could be years away, 
and only after their safety and effectiveness are proved.
    Nevertheless, the Texas researchers say they have crossed a major 
hurdle toward such clinical applications, now that they have shown that 
the technique does not transform healthy cells into cancerous ones, as 
some critics had initially suggested.
    Unlike most normal cells, which have finite lives, cancer cells can 
divide and reproduce indefinitely. One of the markers for cancerous 
activity is the enzyme telomerase.
    ``All cancer cells have figured out a way to become immortal,'' Mr. 
Shay explained. ``Because of that, some researchers have mistakenly 
taken that to mean that if cells are immortalized, they will become 
cancerous.''
    Cancer, he said, is like a runaway car: ``The brakes are 
malfunctioning, the accelerator is stuck, the steering wheel is coming 
off in your hands, and you have a full tank of gas.''
    By contrast, aging cells are like a car that has simply run out of 
gas. ``All we've done is to put a little fuel in the gas tank; the 
brakes, the accelerator and the steering wheel are all still OK.''
    ``Telomerase won't cause cancer; it won't lead to cancer,'' he 
said.
    Mr. Shay's colleague, Woodring Wright, said, ``The abnormalities 
seen in cancer cells are due to other mutations; telomerase merely 
allows the cells to keep dividing.''
    Indeed, further research might help scientists find a way to 
inhibit the telomerase enzyme in cancerous cells. ``That could be a 
potent anti-cancer agent, because it would mean the cancer cells 
couldn't divide,'' Mr. Shay said.
    In January, Mr. Shay and his colleagues showed that structures 
called ``telomeres''--short pieces of DNA at the ends of chromosomes--
are the biological timers that govern how many times a cell is 
programmed to divide in its lifetime.
    Each time a cell divides, its telomeres shorten, like the fuse of a 
lighted firecracker. When the telomeres run out, the cell begins to 
die.
    ``It's very clear that telomeres are the key timing mechanism,'' 
Mr. Shay said.
    But adding the enzyme telomerase to cells actually lengthens the 
telomeres, effectively giving them a new lease on life. Mr. Shay uses 
the term ``immortal'' to mean that a cell has lived at least twice its 
normal lifetime.
    One promising application is producing healthy human cells for use 
in developing and testing new drugs, or screening for genetic diseases. 
A single, healthy human cell, dividing indefinitely, could provide an 
unlimited supply of cells, thereby reducing the number of animals 
required for lab experiments.
    ``This is literally changing the way we study various diseases,'' 
Mr. Shay said.
                                 ______
                                 

              [From the New York Times, January 22, 1999]

             Cell Experiment Offers Hope For Tissue Repair
                           (By Nicholas Wade)
    In a bizarre experiment that demonstrates the surprising plasticity 
of the body's cells, scientists have converted mice's brain cells into 
blood cells.
    The transformation has medical significance because if the human 
body's tissues should prove to be as interconvertible, patients' 
tissues might be repaired from their own cells.
    The result in the mice was obtained with neural stem cells, which 
have the ability to form the three main types of cell found in the 
brain. Each organ of the body is thought to have its own brand of stem 
cells that generate all the organ's specialized cell types.
    But until now, the stem cells were thought to be committed to their 
own organ type and unable to cross over.
    A team of Italian and Canadian scientists, led by Angelo L. Vescovi 
of the National Neurological Institute in Milan, has now found that the 
neural stem cells can metamorphose into the blood-making stem cells of 
the bone marrow.
    Dr. Vescovi's team gave mice sublethal doses of radiation to 
destroy their own blood-making cells, and then injected neural stem 
cells from other mice whose cells carried an identifying genetic tag. 
The neural stem cells found their way to the mice's bone marrow and 
started producing various types of blood cells bearing the genetic tag 
of the donor mouse, the scientists report in today's issue of Science.
    The conversion of neural stem cells into blood cells is 
particularly surprising because brain and blood come from different 
germ layers created in the early embryo. Almost the first visible 
structures in animal embryos are three primary sheets of cells, known 
as the ectoderm, mesoderm and endoderm, from which all the tissues of 
the adult body develop. The brain develops from the ectoderm and blood 
from the mesoderm. Dr. Vescovi's work defies the widely held assumption 
that cells in the three lineages are permanently committed to their 
fate.
    ``It is that trinity that is now being challenged,'' said Ronald 
McKay, a brain cell expert at the National Institutes of Health. Dr. 
McKay said the new result showed that differentiation, the commitment 
of a cell to a specific fate, is not irreversible.
    Dr. Vescovi said he did not know the chemical signals to which the 
neural stem cells were responding but assumed they were influenced by 
local cues in the devastated bone marrow calling for more cells.
    Biologists who work with stem cells hold high hopes for using them 
in medicine. Stem cells, after all, are the natural source of new cells 
when a tissue needs to repair itself.
    The human embryonic stem cells whose first isolation was reported 
last November have been seen as a promising source of new tissue. The 
embryonic stem cells can give rise to all 250 cell types of the body 
and in particular to the lower-level stem cells that generate each 
organ of the body.
    But there are ethical considerations in using embryonic stem cells 
because the cells are derived by destroying an embryo. Also, the cells 
would not be immunologically compatible with a patient unless 
manipulated in ways that have yet to be devised.
    Dr. Vescovi's work suggests that ordinary stem cells, from the skin 
or blood perhaps, could be acquired from the patient, thus avoiding any 
immune rejection problems.
    ``We think you can use skin stem cells to make other cells,'' Dr. 
Vescovi said. If so, skin stem cells could be harvested from a patient, 
and inserted into the bone marrow to make blood cells.
    Dr. Vescovi believes a new branch of medicine is about to develop 
from stem cell biology. ``The resource to heal a sick body lies in the 
body itself,'' he said.
    The recent cloning of animals like mice and sheep is also an 
example of the new plasticity being recognized in cells. In those 
cases, the nucleus of a fully specialized cell was reprogrammed after 
being inserted into an egg cell. In Dr. Vescovi's work, the body's own 
local signals apparently converted the neural stem cells to a new role.
    The plasticity of all these cells is possible because every cell 
contains a full set of the human genes or genome. Each type of cell 
presumably activates its own subset of genes, with all the others being 
switched off.
    Biologists have long assumed the off-switches were put in place 
early in an organism's development. It now seems that the state of a 
stem cell's differentiation is more of a dynamic matter, depending on 
whatever mix of signals it receives in its local environment.
    Stem cells have become accessible to study only in the last 10 
years or so. Distinguishing them from other cells required finding 
markers on their cell surface for which an immune-based tag could be 
developed. Once isolated, the cells have proved extremely unstable, 
either dying or developing into specialized cell types. In the body, 
their behavior is determined by the many cells surrounding them, a fact 
that must be taken into account in cultivating them.
                                 ______
                                 

                [From CNN Interactive, November 9, 1998]

     Heart Researchers Replace Blocked Vessels by Growing New Ones
    Doctors and researchers meeting at the American Heart Association's 
annual conference are considering an experimental treatment called 
angiogenesis, in which scientists use either medication or gene therapy 
to grow new blood vessles in the heart.
    As with most experimental treatments, researchers caution that it's 
still too early for heart patients to get excited about the process.
    But some patients already have experienced positive results.
    Take real estate developer Gil Gilman.
    ``I could not walk across the street without suffering heart pains 
or angina,'' Gilman said. Standard drug treatments, bypass surgery and 
angioplasty were not successful in ending his pain.
    Then doctors at Emerory University in Atlanta offered Gilman 
angiogenesis. Since the treatment, Gilman said, he's gotten stronger, 
and can ``go back to doing basically anything I want to do.''
    Emory researchers have done safety tests of their angiogenesis 
procedure on 58 patients and say they are pleased with the results.
    But scientists say the treatment is still in the early stages of 
development. One concern is that new blood vessels could grow in places 
where they are not wanted, like the eyes and kidneys.
Encouraging results from Tufts study
    A team at Tufts University in Boston use gene therapy on 16 male 
patients with severe blockages. Researchers told the AHA meeting Monday 
the men had less chest pain after the treatment and had to take fewer 
drugs.
    The treatment involved injecting a gene that controls production of 
VEGF, or vascular endothelial growth factor, which instructs the body 
to grow new blood vessels.
    The 16 volunteers, aged 53 to 71, all had suffered heart attacks. 
All had blocked arteries, and all had had either bypass surgery or 
angioplasty to stretch open their clogged blood vessels--many of them 
several times.
    Yet each time the blockages came back. Most of the men had such bad 
chest pain they could not live normal lives.
    After having the VEGF injected into their hearts, all but one of 
the patients reported the reduction in chest pain was ``marked,'' 
starting just 10 days after treatment.
    Again, researchers stressed that more research is needed, but they 
said the potential for treatment is huge.
    Dr. Jeffrey Isner said about 250,000 patients a year have ischemia, 
or blocked blood flow, for which bypass surgery, angioplasty or drugs 
have not worked.
    ``For these patients there is currently no other treatment 
option,'' he told a new conference.
Surgeon says valve repair can extend lives
    Also at the AHA meeting Monday, University of Michigan surgeon 
Steven Bolling said surgical repair of a heart valve can greatly extend 
survival rates for patients with congestive heart failure, which claims 
about 250,000 lives each year in the United States.
    Bolling developed the new procedure as an alternative for patients 
whose only other hope was a heart transplant.

       Cells are units of organisms--organisms are units of life

    Senator Specter. Thank you, Mr. Doerflinger.
    Dr. Rabb, the opinion which you have rendered focuses on 
the proposition that, while cells are units of organisms, 
organisms are units of life. Except for unicellular life, a 
cell does not equal an organism, which is recognized as an 
animal or plant, not a collection of unicells but a 
multicellular cooperative with the emergent properties of a 
whole organism.
    Now, in that context how would you respond to what Mr. 
Doerflinger said, that stem cells may re-cogenerate into what 
could be a whole organism? Is that a possibility?
    Dr. Rabb. I cannot respond on the science, Senator Specter. 
The question that was asked of me was whether, if one were 
dealing with an entity that was not an organism, would one 
violate the human embryo ban, and the answer to that is no, one 
would not violate the ban if one were doing research with an 
entity that was not an organism.
    If the question is whether one can do research with an 
organism that would otherwise be subject to the human embryo 
ban, the answer then again would be no, one could not do such 
research. But the science was not in my domain, the law was; 
and we did not create our own definition of an embryo. The 
definition we used was the one in the statute. As Senator 
Harkin pointed out, the statute defines ``human embryo'' in 
terms of an organism, and that was the question for my office. 
The answer we found through science was that these stem cells, 
not being organisms, are not subject to the ban.
    Senator Specter. So when Mr. Doerflinger says that the 
destructive harvesting of embryos is indispensable, would your 
response be that stem cells can be obtained for this kind of 
research without the destructive harvesting of embryos?
    Dr. Rabb. That is a science question again, Senator 
Specter. What I can say is that, however derived not using 
Federal funds, once derived stem cells are not organisms and 
therefore are not subject to the ban.
    Senator Specter. Well, since it is a science question, Dr. 
Varmus, you enter center stage here. Is it possible to have 
these--acquire these stem cells for the research without having 
the destructive harvesting of embryos?
    Dr. Varmus. At this point, Senator, no. The cells derived 
from embryos do require the destruction of the embryo. 
Obviously, in derivation from fetal tissue the tissue comes 
from a fetus which has already died.
    Let me make a point about the issue that Mr. Doerflinger 
raised with respect to whether pluripotent stem cells in 
culture can become organisms. It is true that sometimes these 
cells can aggregate and may appear like one of the early phases 
in the development of a normal embryo. But to my mind nothing 
would be less ethical than to attempt to ascertain whether or 
not this was indeed a precursor to an organism, a viable 
embryo; that that would require returning that mass of cells to 
a uterus to ask whether it had potential to develop into a 
fetus and a newborn, and the prospect for developing a severely 
impaired individual would be enormous and to my mind a 
reprehensible means of doing research.
    Senator Specter. Dr. Rabb, you made a comment that, except 
for the unicellular life, a cell does not equal an organism. 
Would you explain what you mean by the exception of the 
unicellular life.
    Dr. Rabb. I am going to try. This gets to be science again. 
An organism is, as it has been explained through the science, 
is an individual constituted to carry out all life functions. 
There are some unicellular animals. For those animals, the full 
potential of their lives inheres in a single cell. We are human 
beings. It is the complex interrelationship of all of the human 
systems that make up the organism.
    Senator Specter. Dr. Varmus, I have one final question for 
you. When Mr. Doerflinger makes the point that we have ignored 
other new developments which might lead us to the same avenues 
as stem cells, are you pursuing the kinds of lines of inquiry 
that Mr. Doerflinger suggests at NIH?
    Dr. Varmus. Absolutely, Senator. I am glad you brought that 
up. Many of us were pleasantly surprised by the report that 
appeared in ``Science'' this week, a copy of which I have given 
to your staff, that shows that stem cells taken from the mouse 
brain and grown in culture can be returned to a mouse and 
produce blood cells.
    This indicates a level of plasticity that was unexpected 
and of course a very promising area of research. But I must 
emphasize, this is one report carried out in one way with one 
strain of mice. Whether this formulation or this approach will 
be applicable in other strains of mice, other animals, with 
other types of cells, whether we can identify what is 
responsible for reprogramming the cell, all matters of 
conjecture.
    My view is, yes, we should be pursuing this and many other 
lines of investigation with relation to many kinds of stem 
cells. But to say that we should put our eggs in one basket and 
not in all the available baskets would be a serious mistake.
    Senator Specter. So you are saying that NIH has eggs in 
those other baskets?
    Dr. Varmus. Absolutely.
    Senator Specter. Senator Harkin.
    Senator Harkin. Thank you, Mr. Chairman.
    Mr. Doerflinger, I was just reading an article you had 
written here for the ``National Right to Life News'' which I 
found interesting. Let me just ask you, in vitro fertilization 
is not illegal, is it?
    Mr. Doerflinger. No.
    Senator Harkin. Is it immoral?
    Mr. Doerflinger. In Catholic teaching there are moral 
problems with it, yes. There is a good bit of research, 
however, involving in vitro fertilized embryos that is illegal 
in various States.
    Senator Harkin. I do not think the church has taken a 
position that an infertile couple cannot engage in in vitro 
fertilization. I do not--maybe I am wrong.
    Mr. Doerflinger. Catholic teaching does not accept in vitro 
fertilization as a solution for infertile couples. It urges 
them to pursue fertility treatments that will help their sexual 
union to be procreative if that is what they want, rather than 
to substitute a laboratory procedure for that.
    Senator Harkin. Well, I will have to check, but I did not 
think that they had taken an absolute position against in vitro 
fertilization. So I have in vitro fertilization----
    Mr. Doerflinger. I am pretty close to that situation, 
Senator.
    Senator Harkin. Huh?
    Mr. Doerflinger. Working for the National Conference of 
Catholic Bishops, I am fairly close to that situation.
    Senator Harkin. Well, I am sure you would be. I would hope 
so. But I still, I did not think that they had taken a position 
that said that you cannot use in vitro fertilization. Maybe I 
am wrong. I do not know.
    Mr. Doerflinger. I will be glad to send you the document on 
it.
    Senator Harkin. Am I wrong? Have they taken an absolute 
position on it?
    Mr. Doerflinger. I never like to say that up front to a 
Senator, but I think so, Senator. I will send you the documents 
on it.
    Senator Harkin. Well, I do not know. I mean, you are the 
authority on that. I do not know. Send it to me.
    Mr. Doerflinger. Among the concerns that have been raised 
beyond the Catholic Church about the procedure is the prospect 
for abuses to the embryos that come out of the procedure, the 
culling of high quality embryos, the discarding of embryos, the 
selective reductions that are proposed when too many of the 
embryos implant. These are all part of the----
    Senator Harkin. So we have got in vitro fertilization. At 
least it is not illegal. We have a lot of it going on, and 
obviously there are a lot of leftovers that are frozen. What 
happens to them?
    Mr. Doerflinger. Some are frozen indefinitely. Some are 
ultimately used for later attempts at having a child, and some 
are experimented upon and some are thrown away.
    Senator Harkin. Some are destroyed. Well, if in fact this 
is not illegal and they are in fact, some are destroyed, why 
not use them to get the pluripotent cells that we need to do 
the kind of research that may help us in the future alleviate 
human suffering? I do not understand why we cannot do that.
    Mr. Doerflinger. Well, Senator, I think that is the 
question that we explored a little bit at the last hearing. 
There are lots of things that go on in the private sector that 
are going to go on anyway that Congress has decided not to add 
its encouragement to by giving Federal funds, abortion being an 
excellent example. It is not only legal--I mean, it is more 
legal than destructive embryo research, which is a felony in 
several States. It is defined as a constitutional right. But 
Congress has decided we are not going to use Federal funds to 
give our endorsement to it.
    I think you could just as well say, if you are walking down 
the street and you find a bunch of big tough guys beating up an 
old man, the question arises whether before they are done with 
him you could take his liver because you need it, thus killing 
him a little earlier. I do not think whatever somebody else is 
doing out there in the private sector that they are going to do 
anyway has much influence on what Congress has to decide in its 
policy decision on what to promote.
    See, in this case, this is not a case analogous to the 
fetal tissue situation where the abortion has been done and, as 
Henry Waxman said in 1993 in the House floor, the only question 
left is whether to throw away the tissue that is left after the 
fetus is dead or make use of it. Here is a case where the 
researchers' harvesting procedure does the destruction itself. 
That is a very different moral proposition.
    Senator Harkin. But it is going to take place, as I said, 
anyhow.
    Mr. Doerflinger. It is going to take place anyway. Senator, 
you and every other Senator in the Senate voted in 1997 to 
reject Federal funding of euthanasia, even though all of those 
people are going to die pretty soon anyway. But it makes a 
difference whether they are going to die of some other cause or 
whether the government is going to help kill them.
    Senator Harkin. Well, as you said here in this article, you 
said that such experiments that we are talking about here 
create new human life. I thought we got through that. 
Organisms, these are not organisms. They cannot develop into 
full human life. Every scientist I have ever asked that 
question to says that. Yet you seem to want to bring it back 
across that boundary line again, and I just do not understand 
that.
    Mr. Doerflinger. I think what I was saying, Senator, was 
there is a factual uncertainty about one of these experiments, 
Dr. Gearhart's, which can be settled in a factual way. It is an 
uncertainty he himself has. The answer that Dr. Varmus has 
given is intriguing, because if we really do not know and there 
is no ethical way to find out, that might answer the question 
in the direction of saying we cannot fund it then.
    But my broader question was simply that HHS gave an answer 
to that question which is probably right as far as it goes, but 
it is the wrong question, because the embryo research rider was 
not intended only to say that you cannot use Federal funds for 
the destructive act itself. It was designed to prevent Federal 
funding of an entire research project in which these are 
destroyed, even if they are destroyed with private funds.
    Senator Harkin. Well, I disagree with that interpretation. 
I adamantly disagree. That may be your interpretation. I do not 
believe Congress--you would have to show me report language or 
anything else that indicates that we intended it to be that 
broad and that encompassing. I do not believe that.
    Mr. Doerflinger. You have two clauses there right next to 
each other. The first one says you cannot use Federal funds for 
creation of embryos. If your interpretation is right, I cannot 
think of a blessed reason why they did not just say Federal 
funds cannot be used for destroying embryos. They did not say 
that. Instead they said--they used an entirely different phrase 
right next to the first one saying, cannot be used for research 
in which embryos are destroyed or discarded.
    Now, that cannot mean the same thing as the first clause 
because it is very deliberately written more broadly.
    Senator Harkin. I have to think. You lost me on that one.
    Mr. Doerflinger. If you want to rewrite the rider, then we 
can have a debate about that.
    Senator Harkin. This is it right here. ``None of the funds 
made available by Public Law 104-91 may be used for: [1] the 
creation of a human embryo or embryos for research purposes or 
[2] research in which a human embryo or embryos are destroyed, 
discarded, or knowingly subjected to risks of injury or death 
greater than that allowed for research on fetuses in utero 
under 45 CFR,'' etcetera.
    ``For the purposes of this section,'' I will read one more 
time, ``the phrase' human embryo or embryos' shall include any 
organism not protected as a human subject under 45 CFR 46 as of 
enactment of this act,'' etcetera, etcetera, etcetera.
    Now again, I think that is the essence of the finding at 
HHS. It is clear that these are not organisms----
    Mr. Doerflinger. That the stem cells are not organisms.
    Senator Harkin (continuing). and as such cannot be covered 
by that law, Mr. Doerflinger. Now, if you want to change the 
law----
    Mr. Doerflinger. I am not talking about the stem cell being 
an embryo. I am talking about the stem cell that you have to 
kill to get the stem cells----
    Senator Harkin. Wait a minute.
    Mr. Doerflinger [continuing]. as an integral part of that 
research protocol.
    Senator Harkin. You are saying stem cell you have to kill 
to get the stem cells. I do not understand that, what you just 
said. You said the stem cell you have to kill to get the stem 
cell.
    Mr. Doerflinger. No, I said the embryo you have to kill to 
get the stem cells. The stem cells are simply the inner cell 
mass of an embryo. The way the stem cells is obtained is by 
doing microsurgery on an embryo and sucking out the inner cell 
mass to provide stem cells for culture.
    What I am saying is the destruction of that initial embryo 
in two of the three experiments we are talking about, because 
Dr. Gearhart's experiment is using fetal tissue, but in Dr. 
West's and Dr. Thomson's experiments an integral part of the 
research protocol is you must arrange for these embryos to be 
destroyed by the harvesting of these cells. It is not after the 
embryo is dead. It is what kills the embryo. It seems to me 
that that is what Congress was intending to prevent.
    Senator Specter. Senator Harkin, do you have further 
questions?
    Senator Harkin. No, thank you very much, Mr. Chairman.
    Thank you, Mr. Doerflinger.
    Senator Specter. Thank you.
    Senator Hollings.
    Senator Hollings. Would you care to comment, Dr. Varmus.
    Dr. Varmus. I think the point is the law to our minds reads 
quite clearly, and it is not our job to try to discern intent 
when intent is not described by report language or other means 
of discernment. So our view is that there is a very clear 
distinction to be made between research in which stem cells 
that have been developed in one laboratory by one procedure are 
then used by other investigators to support other kinds of 
research that is not research in which an embryo, an organism, 
is subjected to risks greater than those that are dictated by 
other statutes.
    Senator Hollings. Thank you, Mr. Chairman.
    Senator Specter. Thank you, Senator Hollings.
    We are now slightly past 10 o'clock, so we are going to 
have to adjourn. We thank you very much for coming again today, 
and this is obviously going to be an ongoing matter of great 
public interest as we pursue the steps which are set up. We 
appreciate your participation, Mr. Doerflinger, to give us your 
analysis. You have immunity here when you criticize Senators. 
You can say Senators are wrong. That comes under----
    Senator Hollings. We hear that every day.

                         CONCLUSION OF HEARINGS

    Senator Specter. Senator Hollings is accurate about that. 
But you have a privilege to make those statements. We are here 
to have an exchange, and we appreciate your incisiveness and 
your study and your knowledge of the field.
    We thank you, Dr. Varmus, Dr. Rabb, and Dr. Meslin, and 
stay tuned. Thank you all very much for being here, that 
concludes our hearing. The subcommittee will stand in recess 
subject to the call of the Chair.]
    [Whereupon, at 10:02 a.m., Tuesday, January 26, the hearing 
was concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]

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