HJR 588: Medical, Ethical, and Scientific Issues Relating to Stem Cell
Research Conducted in the Commonwealth
The second meeting
of the Joint Subcommittee was held at the Fairfax County Board of Supervisors
Auditorium and featured an impressive panel of experts.
DR. GARY S. FRIEDMAN
Dr. Friedman is a
physician with broad transplantation experience, having directed a transplant
program for 10 years and published extensively on clinical transplantation,
transplant immunology, cellular pharmacology, and hematological issues
in clinical transplantation. He is a founder of International Regenerative
Medicine (a consortium focused on development of therapeutic applications
of human stem cells), the Director of the Center for Regenerative Medicine
in Morristown, New Jersey, and a trustee of the New Jersey Stem Cell Research
& Education Foundation.
Dr. Friedman began
by noting historical landmarks in transplantation, including the first
successful kidney transplant performed in 1954 and the expansion of nonembryonic
stem cells to include stem cells from umbilical cord blood in the 1980s.
He also noted that the Organ Procurement and Transplantation Network (OPTN)
was established by Congress under the National Organ Transplant Act (NOTA)
of 1984; the United Network for Organ Sharing (UNOS) of Richmond was founded
in 1984, and became the federal contractor for the operation of the OPTN;
and NOTA included language that led to the formation of the National Bone
Marrow Donor Program.
The bone marrow program
was established to provide a data base of bone marrow tissue types in
order to provide more access to therapies using stem cells for cancers
and other disorders. UNOS, on the other hand, operates to provide solid
organs on a need basis in an egalitarian manner. Dr. Friedman noted that
physicians who perform transplants, solid organs or stem cells, are reimbursed
for their services. He noted that federal law prohibits the sale of human
tissue. Less than 20 percent of the people who are waiting for transplants
actually undergo the procedure and time on the waiting list for solid
organs has increased from one to two years to five to eight years in many
Dr. Friedman became
interested in stem cell therapy, because he felt that the life expectancies
of patients waiting for organ transplants could be extended with stem
cell therapy and that organ supply and demand issues could be ameliorated.
He also noted that many uses have been found for stem cells that can be
provided through umbilical cord blood. He expressed concern that procurement
programs for solid organs do not include the recovery of bone marrow (which
contains stem cells that can differentiate into blood, heart muscle, and
other tissues) on a regular basis, because harvesting of bone marrow is
not reimbursed. Dr. Friedman supports the harvesting of bone marrow by
transplant procurement teams, as well as the collection and banking of
cord blood. This would allow stem cell therapy to be available on a 24
hour basis in order to respond to the growing patient therapy needs of
the many Americans waiting for transplantation of stem cells or solid
Dr. Friedman stated
that using embryonic stem cells requires massive culture of the cells
and involves risk of tumor development, specifically teratomas, or even
malignancy. Donor cells may migrate and reproduce in any part of the body
of a patient receiving stem cell therapy. This phenomenon has been observed
when embryonic stem cells are transplanted, but not with adult stem cells.
Because of this, care must be taken to avoid poor patient outcomes and
Dr. Friedman emphasized that he believes the existing organizational structure
for organ and bone marrow collection should be used for cord blood banking,
as well as for the harvesting and banking of donor bone marrow in order
to provide plentiful sources of stem cells for use in regenerative medicine.
DR. JOHN D. GEARHART
Dr. Gearhart, one
of the preeminent stem cell researchers in the United States, is the C.
Michael Armstrong Professor, Medicine of the Institute of Cell Engineering,
Johns Hopkins University; professor of gynecology and obstetrics and of
physiology at the Johns Hopkins University School of Medicine; and holds
a joint appointment in the Department of Biochemistry and Molecular Biology
at the Bloomberg School of Public Health. He led the Johns Hopkins University
research team responsible for first deriving human pluripotent stem cells
in 1998. Much of his research has been focused on how genes regulate the
formation of tissues and embryos, particularly in examining mental retardation
and other congenital birth defects.
Dr. Gearhart began
by responding to concerns about the formation of teratomas when embryonic
stem cells are used in transplantation. He stated that he wanted to set
the record straight, that "from the experimental side when you isolate
derivatives, you don't put in a graphed embryonic stem cell. It will lead
to a tumor...." He noted that the experiments must be performed correctly,
making sure grafts do not contain embryonic stem cells, because the capacity
of the stem cells to divide and differentiate is a major safety issue.
The Johns Hopkins program deals with various sources of stem cells, including
adult sources, umbilical cord blood, embryonic stem cells, and stem cells
derived from bone marrow. The research group seeks to address many stem
cell biology issues; however, most of the research is preclinical and
experimental. Very little of the research has resulted in clinical trials,
which Dr. Gearhart believes is appropriate. He observed that the public
wants therapies right now; however, the development of medical applications
will take time.
Dr. Gearhart focused
on the uniqueness of the stem cell-embryonic or adult-and its capacity
to self-renew (i.e., it can produce another cell like itself and specialize
into another cell type). Some stem cells can divide only once and others
can divide many times, producing many different cell types [See illustration
below]. This intricate and difficult problem is the central focus of stem
cell science-trying to figure out which stem cells have the capacity for
generating specific tissues. The only major clinical application of stem
cells, at present, uses stem cells derived from bone marrow, which contains
two kinds of stem cells-hematopoietic and mesenchymal. Dr. Gearhart noted
that regardless of the source, certain criteria must be met in stem cell
research: (i) self-renewal, (ii) stability, (iii) capacity to multiply
and specialize, and (iv) reproducible results for quality control.
The Johns Hopkins
research group is comparing various stem cell sources, which is the only
way to find out what works. He explained that when you graft bone marrow,
you are putting both types of stem cells (hemapoietic and mechenymal)
into the individual, and the cells can migrate to any organ in the body
and may contribute to a variety of tissues. To illustrate, he posed the
question: "Are the cells functional in the tissues to which they
contribute or are the cells simply residing in the tissue?" A neuron
stem cell, for example, will only produce the type of cell from the brain
region from where it is taken, but will not reproduce all other types
of brain cells.
there are probably over 250 validated embryonic stem cell lines, of which
22 appear on the President's list. Harvard University's Stem Cell Institute
has developed approximately 17 embryonic stem cell lines. The number of
stem cells being used in the United States is unknown, because private
funds are being used to derive stem cell lines that are not eligible for
federal funding. Dr. Gearhart emphasized that studies of adult and embryonic
stem cells, thus far, in the Johns Hopkins laboratory research model,
showed that embryonic stem cells work better .
Speaking to somatic cell nuclear transfer, Dr. Gearhart noted that scientists
agree that reproductive cloning of human beings should not be allowed.
The term "therapeutic cloning" has been used since 1999, and
scientists regret coinage of the term. The actual process would be to
match an embryonic stem cell line by doing somatic cell nuclear transfer
from the patient to an oocyte and then generating a blastocyst. The resulting
stem cell would be a precise match for the patient, eliminating host-graft
Dr. Gearhart concluded
that studies of human embryonic stem cells will result in important drug
developments, but the stem cell controversy will continue. Only further
study of both adult and embryonic stem cells will reveal which stem cell
source works better. The United States has lost the lead in stem cell
research and therapy development to Australia, Singapore, Korea, Israel,
and the United Kingdom. Many of our country's brightest students are looking
for postdoctoral positions in these countries, because of the cutting-edge
research and the availability of government and private funding.
DR. JONATHAN D. MORENO
Dr. Moreno is the
Emily Davie and Joseph S. Kornfeld Professor of Biomedical Ethics and
the Director of the Center for Biomedical Ethics at the University of
Virginia; past president of the American Society for Bioethics and Humanities;
a bioethics advisor for the Howard Hughes Medical Institute; and has published
over 200 papers, numerous reviews, and six books on subjects ranging from
human experimentation to clinical studies and practice. Dr. Moreno was
co-chair with Dr. Richard O. Hynes of the National Academy of Science
Committee on Guidelines for Human Embryonic Stem Cell Research.
Dr. Moreno's presentation
was focused on the National Academies recently issued human embryonic
stem cell research guidelines, now published as a book. He emphasized
that the National Academies are not government agencies, although they
are chartered by the federal government and 90 percent of its work is
requested by Congress or the executive branch. The embryonic stem cell
guidelines project was funded by two private foundations and National
Academies' funds. The National Academies embryonic stem cell guidelines
have no legal standing, only offer intellectual and professional persuasion.
The Academies only address issues of national significance, mandated by
Congress or the executive branch, or issues in which there is a perceived
public need as expressed through the scientific communities.
Dr. Moreno cited
the many reasons for developing embryonic stem cell guidelines:
- Significant public
support for human embryonic stem cell research.
- Diverse funding
available for stem cell research-private, federal and state.
- Scientific concerns
relating to the hodgepodge of federal regulations.
- Lack of regulation
of privately supported human embryonic stem cell research.
- Public and scientific
uncertainty about the appropriate procedures for conducting stem cell
The purpose of the
guidelines is to encourage responsible stem cell practices, including
the use of stem cells derived from surplus blastocysts from in vitro fertilization
clinics, stem cells derived from blastocysts derived from donated gametes,
and stem cells derived from blastocysts produced using nuclear transfer.
The guidelines address ethical and legal concerns and encompass policy
issues relating to the use of human embryonic stem cells for research
and therapy. Although the guidelines address human embryonic stem cell
research and therapy, the recommendations could be applied to other human
stem cell research, including adult stem cells, fetal stem cells or embryonic
Among the issues
addressed were donor recruitment (informed consent, compensation, conflicts
of interest, confidentiality, risks of oocyte retrieval, and use of genetic
information); stem cell characterization and standardization; safety in
handling and storage of blastocysts and stem cells; sharing of materials
between laboratories; appropriateness of and limitation on human embryonic
stem cell research and therapy; and safeguards against exploitation or
Having already recommended
in 2002, that "[h]uman reproductive cloning should not now be practiced.
It is dangerous and likely to fail," the National Academies' position
continues to be that human reproductive cloning should not be conducted.
The recommendations include:
- Review by an Institutional
Review Board, informed consent of all donors, severing donation decisions
from all clinical decisions, prohibition of compensation or reimbursement
to donors except for direct expenses, no commercialization (sale or
purchase) of donated materials, and protection of donor privacy.
of institutional oversight committees and an independent national panel
to evaluate and revise the adequacy of the guidelines, as necessary.
The institutional oversight committees, referred to as Embryonic Stem
Cell Research Oversight (ESCRO) committees were recommended to include
public and expert representation.
- Certain research
with embryonic stem cells should not be permitted at this time, including
in vitro culture of any intact human embryo beyond 14 days (a standard
that has been accepted by most scientists), any research in which human
embryonic stem cells are introduced into nonhuman primate blastocysts
or in which any embryonic stem cells are introduced into human blastocyts,
and that animals into which human embryonic stem cells have been introduced
at any developmental stage should not be allowed to breed.
The mechanisms for
compliance with the guidelines are voluntary adoption of policies/practices
that are consistent with the recommendations and the imposition of appropriate
institutional sanctions for noncompliance. The guidelines have been endorsed
by the presiding or executive officers of many prestigious institutions
and organizations, and hopefully, other states and entities will also
consider adopting the guidelines.
REV. TADEUSZ PACHOLCZYK
is the Director of Education at the National Catholic Bioethics Center
in Philadelphia, an ethicist, and a Catholic priest for the diocese of
Fall River, Massachusetts. Father Pacholczyk received four undergraduate
degrees in philosophy, biochemistry, molecular cell biology, and chemistry
from the University of Arizona; a doctorate in neuroscience, focusing
primarily on cloning genes for neurotransmitter transporters that are
expressed in the brain, from Yale University; and studied for five years
in Rome conducting advanced work in theology and bioethics, examining
the question of delayed ensoulment of the human embryo. He is frequently
asked to speak regarding stem cells, cloning, and other biotechnologies,
and has testified before the Massachusetts and Wisconsin State Legislatures
and participated in a Pontifical conference on these subjects.
presentation focused on the moral arguments and ethical considerations
raised by stem cell research, the proper direction for issues addressed
by the legislatures in the future, and whether medical efficiency should
trump and triumph over ethics. He began with a short vignette about a
mother teaching her young daughters a lesson after not allowing them to
see a movie which contained a little bit of immorality. The girls' mother
showed them how a little bit of bad can ruin a lot of good by baking cookies
with just a little of their pet rabbit's droppings in them.
Dr. Pacholczyk applied the analogy to embryonic stem cell research and
warned that in the same way that the rabbit's pellets ruined the cookies,
society's attempts to cover up or ignore a little bad in something good
is an effort to pretend that the "bad" does not really exist.
posed the question, "What is wrong with a little bit of embryo destruction
to help the greater good?" He asserted that everyone in the room
came from an embryo and acknowledged that an embryo is a very small object.
He insisted, however, that once everyone accepts the fact that they started
out as an embryo, the focus is drawn to a discussion of whether all human
beings are created equal, regardless of size. Thus, if all human beings
are created equal, the size of the human embryo doesn't matter; consequently,
the destruction of human embryos to help other humans is wrong. Father
Pacholczyk disputed the argument made by those in favor of embryonic stem
cell research that there are hundreds of thousands of embryos in a deep
freeze in vitro fertilization clinics that will be thrown away if not
used. He stated that it is important to realize that the "discarding
versus using for research" argument is a lever to pry open the door
to what he feels is the ultimate research goal--therapeutic cloning. Father
Pacholczyk emphasized that discussion is very important and noted that,
in his opinion, in vitro fertilization "slipped under the radar screen."
He commented that the taking of a human embryo was "innocent life"
compared with society taking human life as a matter of law through war
and the death penalty.
discussed alternatives to embryonic stem cell destruction, such as back-differentiating
adult stem cells. Dedifferentiation (reprogramming of a specialized cell
or tissue to a simpler, unspecialized form) of adult stem cells was postulated
as a solution to the human embryonic stem cell controversy, because a
human embryo would not have to be destroyed. The dedifferentiated adult
stem cells could be differentiated forward in a new direction and have
the potential to become many different types of cells.
concluded by proposing that the United States should not be concerned
with being at the forefront of stem cell research, but the critical issue
is for the country to lead in an ethical sense. He fears that the raw
power of science will lead to exploitation, and that we should take the
high ground, not run after the herd.
PRESENTATION BY DR. DAVID A. PRENTICE
Dr. Prentice is
a Senior Fellow for Life Sciences at the Family Research Council in Washington,
D.C., and an Affiliated Scholar for the Center for Clinical Bioethics
at the Georgetown University Medical Center. Dr. Prentice held positions
at the Los Alamos National Laboratory; the University of Texas Medical
School at Houston; and the Indiana State University School of Medicine.
Dr. Prentice is an internationally recognized expert on stem cell research
and cloning and was selected by the President's Council of Bioethics to
write a comprehensive review of adult stem cell research for the Council's
2004 publication "Monitoring Stem Cell Research."
Dr. Prentice began
his presentation by discussing the current and potential problems with
embryonic stem cells, noting that these stem cell lines are difficult
to establish, handle, and maintain and carry the possibility for causing
tumors and tissue destruction. Dr. Prentice presented the members with
evidence that some adult stem cells show pluripotent capacity. Scholarly
articles have shown that adult stem cells from bone marrow can form new
neurons in the human brain and that bone marrow stem cells can go on to
form all body tissues. Studies have shown that placental amniotic stem
cells potentially form any type tissue without producing tumors. Human
cord blood stem cells, which are young stem cells, have been shown to
Dr. Prentice continued
by describing studies from around the world in which adult stem cells
have been demonstrated as being effective in tissue repair. The first
clinical trials are under way to demonstrate that adult stem cells from
brain, bone marrow, and umbilical cord blood provide therapeutic benefit
after stroke. Clinical trials have been started in Australia and Portugal
to determine whether adult stem cells are capable of re-growth and reconnection
in the spinal cord.
In describing the
current uses of adult stem cells, Dr. Prentice enumerated treatments for
cancers, autoimmune diseases, anemias, immunodeficiencies, bone/cartilage
deformities, corneal scarring, stroke, repairing cardiac tissues after
heart attack, Parkinson's disease, growth of new blood vessels, gastrointestinal
epithelia, wound healing, and spinal cord injury.
Dr. Prentice concluded
by highlighting the advantages of pursuing adult stem cell research: adult
stem cells are the most promising source for treatments; they multiply
almost indefinitely, providing numbers sufficient for clinical treatments;
they have proven successful in laboratory culture, in animal models of
disease and current clinical treatments; they have the advantage to "home
in" on damage; and they avoid problems with tumor formation, transplant
rejection, and ethical quandary.
The September 21
meeting of the joint subcommittee will focus on stem cell research and
related activities being conducted in Virginia. The materials distributed
at the August meeting may be accessed on the study's website, including
audio-streaming of the presentations.
The Hon. R.G. Marshall