HJR 588: Medical, Ethical, and Scientific Issues Relating to Stem Cell
Research Conducted in the Commonwealth
November 15, 2005
The final meeting
of the joint subcommittee completed review of stem cell research activities
in Virginia and included a public hearing, information on cord blood banking,
and a work session.
REVIVICOR, INC.
Dr. David L. Ayares
is the chief executive officer of Revivicor, Inc., based in Blacksburg.
Revivicor, a recent spin-off company of PPL Therapeutics, is a biopharmaceutical
company that has produced products used in treatment, for example, alpha-1-antitrypsin
(AAT), which was awarded "orphan drug" status by the federal
Food and Drug Administration in 1999 has been used in clinical trials
for treatment of hereditary emphysema and cystic fibrosis. Revivicor is
a world leader in animal cloning technology, being a subsidiary of the
company in Scotland that produced Dolly, the Sheep, the first cloned animal.
Revivicor concentrates on advancement of biomedical products and regenerative
medicine, with a diverse product development pipeline focused on creating
genetically modified pig organs and cells for xenotransplantation applications
(between species, such as from pigs to humans), stem cell therapies for
diabetes, and development of human polyclonal antibodies from genetically
modified livestock for biological warfare countermeasures.
Dr. Ayares' research
at Revivicor has primarily focused on pigs in order to develop a solution
to the donor organ shortage for patients needing transplants. Revivicor
is responsible for the first successful cloning of pigs as well as the
first successfully cloned knockout pigs?pigs that are lacking the gene
associated with hyper acute rejection of xenografts (use of tissue from
one species to treat another species). The goal of this animal cloning
technology is to produce pig tissue that can be used in humans without
being rejected. The gene that was "knocked out" or removed from
the pigs is responsible for production of a sugar on pig cell surfaces
that is foreign to the humans and will, therefore, trigger an immune response
leading to hyper acute rejection by humans within minutes of the transplant.
Bearing in mind that
even human to human transplants require the use of immunosuppressants,
drugs that inhibit the body's immune system to control graft versus host
disease, the goal of this research is to produce organs and cells that
are tolerized, i.e., modified so as to be histocompatible with the human
recipient. In other words, Revivicor's mission is to produce pig tissue
and cells that can be used to treat humans without requiring lifelong
treatment with immunosuppressants, e.g., pancreatic islet cells for the
treatment of diabetes.
Revivicor has been
awarded four grants from the Advanced Technology Program (ATP) of the
National Institute of Standards and Technology within the United States
Department of Commerce, a federal grant initiative to promote the technology
development in private industry. Dr. Ayares explained that the federal
ATP is very important to private research efforts, as venture capital
is difficult to obtain for the basic research that is necessary to develop
pre-clinical biotechnology. Because basic research is time consuming and
the outcomes are unpredictable, investors are difficult to attract.
In 2000, PPL Therapeutics
(Revivicor's parent company) was awarded a $1.9 million ATP grant to fund
research relating to the production and differentiation of pluripotent
stem cells without using embryos. This research was exclusively conducted
on nonhuman species, i.e., pigs, and involved changing or transdifferentiating
pig skin fibroblast cells into pig embryonic-like stem cells. The concept
was considered a viable option for deriving large numbers of pluripotent
stem cell lines without the supply constraints acknowledged to exist with
the embryonic-derived lines. Somatic cell nuclear transfer, an expertise
of Revivicor, was used on the readily available skin cells to transdifferentiate
the pig skin fibroblasts to stem cells. However, the development of the
stem cells was limited and the cultures did not continue to divide indefinitely.
Although the research goal was not reached before the grant expired, much
was learned, and the goal of transdifferentiating skin cells into stem
cells may still be successful as some recent research appears to indicate.
CORD BLOOD BANKING
Dr. Curtis Thorpe,
technical advisor to the joint subcommittee from the Virginia Department
of Health, presented information on cord blood banking that had been researched
by staff. The joint subcommittee had asked whether other states or countries
supported cord blood banking systems and the feasibility and cost of establishing
a statewide umbilical cord blood banking system in Virginia.
Other States'
Cord Blood Banking Initiatives
Three states, Florida, Massachusetts, and New Jersey, have different models
of public cord blood banks.
Florida's program
is a consortium between the University of Florida, University of Southern
Florida, the University of Miami, and the Mayo Clinic in Jacksonville
and provides for the collection, screening for infectious and genetic
diseases, tissue typing, and cryopreservation of cord blood as a public
resource. The Florida program offers the opportunity to donate to the
pregnant woman at the time of hospital or birthing facility admission,
requires written disclosure from providers who financially benefit from
cord blood, and authorizes the consortium to charge reasonable fees to
recipients.
Massachusetts' program
is a partnership with the University of Massachusetts Medical School at
Worchester, established as a public cord blood bank for umbilical cord
blood and placental tissue donated by maternity patients at certain participating
hospitals. Licensed hospitals must inform pregnant women of the opportunity
to donate cord blood and educate maternity patients about cord blood banking.
Research institutions may agree to pay the estimated expenses of the collection
and storage of the donated umbilical cord blood and placental tissues.
Massachusetts also established a 15-member Biomedical Research Advisory
Council to make recommendations to the governor about biomedical research
relating to cord blood and placental tissue.
New Jersey's program
provided for a $ 5 million loan to establish the New Jersey Cord Blood
Bank to the Coriell Institute for Medical Research, an internationally
known, not-for-profit biomedical research institution with a long history
of cell banking, cryogenic storage, and retrieval of human cell cultures.
Strong relationships between the cord blood bank and the collecting hospital
are established, and written informed consent must be obtained from any
woman choosing to donate cord blood. The Coriell Institute for Medical
Research is required to repay the state loan as reimbursement is received
for cord blood released for therapy.
In some states, such
as Maryland, cord blood banking is regulated by requiring hospitals to
allow pregnant patients to donate umbilical cord blood to certified cord
blood banks and prohibiting charges for the donation. Further, Maryland
law notes that employees who have bona fide religious objections cannot
be required to collect cord blood and hospitals are not required to make
patients' arrangements for cord blood donations.
Other Countries'
Cord Blood Banking Initiatives
In a growing number of countries across the world, cord blood banking
initiatives have been established. Brazil, for example, has a public cord
blood bank at one maternity hospital in Rio de Janeiro. Colombia recently
established a cord blood banking program through the University of Antioquia.
India also recently
announced a government cord blood banking initiatives in four locations
through a contract with a private firm. In Korea, the Seoul Cord Blood
Bank is not a government program and is run by the same private firm that
operates in India. Singapore has a government-supported cord blood bank,
established in 2004, that provides free cells to any child whose cord
blood has been donated; others are charged for the units. Australia has
a national network of cord blood banks in Melbourne, Sydney, and Brisbane
and registers cord blood in the Australian Bone Marrow Registry.
The European Union
forbids profit-making from the sale of body material; however, operating
expenses may be recovered. France prohibits private cord blood banking,
considering cord blood a national resource and having only three hospitals
that collect it. In the United Kingdom, the National Health Service collects
cord blood for the public good, with 80 or more units having been released
for transplantation. Italy prohibits private cord blood banking and has
a network of public cord blood banks maintained by its national health
system.
National Marrow
Donor Program
The United States' National Marrow Donor Program is part of a world-wide
network of 500 medical facilities that searches for a donor or cord blood
match when a patient needs a transplant and facilitates an average of
200 bone marrow or blood cell transplants each month. The National Marrow
Donor Program has a registry of more than 45,000 cord blood units in cord
blood banks across a number of states.
Cord Blood Banking
in Virginia
In Virginia only approximately 5 percent of umbilical cord blood is not
being banked in the medical schools, primarily for the use of pediatric
oncologists for children cancers. Most stored cord blood in Virginia is
being deposited at parents' expense in private storage facilities.
Process for a
Virginia Cord Blood Banking Initiative
The first step for developing a public cord blood banking initiative in
Virginia would be to develop a database of existing cord blood supplies
and perhaps legal authority to access any privately banked cord blood
during an emergency. In order to store umbilical cord blood to meet a
statewide emergency, a capacity of at least 40,000 doses would be needed,
with the cells stored for up to five years to ensure recycling to maintain
cell integrity.
Drawing from other
states' programs as examples, a cord blood banking program could be integrated
into an existing cell storage infrastructure or started as a new cord
blood initiative under state supervision, or contracted with a private
sector provider. Integration into an existing system would probably be
the least expensive option, involving coordination with existing facilities
at Virginia Commonwealth University's School of Medicine, the University
of Virginia's School of Medicine, and the Eastern Virginia Medical School
and its contracting hospitals, as well as the private hospital systems
in Western and Northern Virginia?for a total of five sites covering all
regions of the Commonwealth.
Site requirements
would be approximately 400 to 500 feet of space, at least 2 liquid nitrogen
freezers, at least 2 vent hoods, and access to fluorescent cell sorting
and tissue typing. Costs at each of the five sites are estimated as $200,000
for equipment, two laboratory technicians per site at approximately $50,000
each plus benefits; and supplemental salary for an existing supervisor
to manage an additional program. The approximate start up costs for the
initial year would be $1.5 to $2 million, with maintenance costs estimated
at $1 million per year, and monitoring costs unestimated. If implemented,
a collaborative arrangement of this kind would make cord blood accessible
to all parts of the state.
Establishing a new
system would be more expensive and may require a new building or a renovated
structure specifically designed for the cord blood bank. The new system
would also require equipping and would probably have to be a GMP facility
with a level V laboratory that is strictly regulated. The costs of such
a facility and system could be as high as $20 million to initiate.
A third operation
would be to contract with a private stem cell storage company, which would
require a bid process and could present issues relating to control of
the cord blood and access in any statewide or regional emergency.
With any of these
options, various issues relating to patient privacy, recycling of cells
over five years old as new cells enter the system, and perhaps sale of
exiting cells to research programs or others to offset costs.
PUBLIC HEARING
Three speakers registered
and spoke during the public hearing and two statements were submitted
and read for the record. The submitted statements were from Dr. John T.
Bruchalski, an obstetrician/gynecologist practicing in Fairfax, in support
of cord blood banking and adult stem cell research and Ms. Moira Hall,
a 20 year old diagnosed with Hodgkin's Lymphoma. She was treated with
high-dose chemotherapy with stem cell support using cells donated by a
twin sister; when this treatment was not successful, she received a second
transplant of cells donated by a younger brother, which resulted in successful
remission.
Representing the
Virginia Society for Human Life, Dorothy Tims expressed strong opposition
for human embryonic stem cell research and support for the use of adult
stem cells. She stated that "[t]he weakest and most vulnerable member
of the human family?the embryo?should not be the subject of scientific
experimentation" and that "[i]t is never morally or ethically
justified to destroy one human being in order to possibly save another."
Ms. Tims described the advances that have been and are being made in adult
stem cell research, using alternatives to embryonic stem cells such as
cord blood, bone marrow, and neural stem cells. She called for the use
of research money and efforts to be directed to the adult stem cell therapies
that are "free of the ethical dilemmas associated with destructive
human embryo research." Ms. Tims closed by stating that the VSHL
encourages continued efforts in the scientific community to develop treatment
for life threatening and life limiting diseases in a manner free from
ethical issues.
Mr. Richard M. Doerflinger,
Deputy Director of the Secretariat for Pro-Life Activities, United States
Conference of Catholic Bishops, presented a notebook of supplemental materials
to the joint subcommittee. Mr. Doerflinger, while noting that the Catholic
Church does not oppose stem cell research, stated that destruction of
human life at any stage was opposed, thus, human embryonic stem cell research
is opposed. He noted that adult stem cells and stem cells from cord blood
provide viable alternatives and cited the many advances in the research
and therapies using adult stem cells. He also mentioned the drawbacks
to embryonic stem cell research, such as the development of teratomas.
Mr. Doerflinger said that even the embryonic stem cell researchers now
have reduced expectations from their studies. He also reflected that excess
embryos are not available in the numbers required to produce the number
of cell lines desired, which would take the destruction of millions of
embryos. Dr. Doerflinger described the potential for exploitation of women
in the creation of the embryos, including the current controversy involving
Korean research, including reports that one laboratory technician donated
oocytes for the creation of the embryos used for the research. Mr. Doerflinger
described human reproductive cloning, which almost all groups oppose,
as potential fetus farming.
Dr. Michael Valente,
a physician practicing neurology in the Commonwealth, who came as a taxpaying
citizen who objects to the possibility of using state tax money to fund
human embryonic stem cell research. He stated that embryonic stem cell
research using mice has not produced any cure for diseased mice. He also
said that adult stem cells from bone marrow, pancreas tissues, and discarded
placentas, even nasal epithelium, are being used to treat diabetes, heart
disease, leukemia, and other diseases. Dr. Valente stated that he sees
value in taxes when used for necessary services, but he is opposed to
using public money for unproven research. He said that his medical background
provided him special insight in this regard, and that scientists are moving
away from embryonic stem cell research to the use of adult and umbilical
cord blood stem cells
RECOMMENDATIONS
Having received an
issues analyses prior to the meeting that also set out six broad topics
for discussion, the joint subcommittee decided on motion and a unanimous
vote that the only recommendation for the 2006 Session would be the establishment
of a Virginia Cord Blood Banking initiative. Included in the motion was
that the joint subcommittee would seek continuation of the study for another
year.
Chairman:
The Hon. R.G. Marshall
For information,
contact:
Norma Szakal,
DLS Staff Attorney
Website:
http://dls.state.va.us/stemcell.htm
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