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Testimony on Stem Cell Research by Gerald D. Fischbach, M.D.,
Director, National Institute of Neurological Disorders &
Stroke and Allen M. Spiegel, M.D., Director, National Institute
of Diabetes and Digestive and Kidney Diseases, National Institutes
of Health, U.S. Department of Health and Human Services
Before the Senate Appropriations Subcommittee on Labor,
HHS, Education and Related Agencies
September 7, 2000
Mr. Chairman, Senator Harkin, and Members
of the Subcommittee, I am Dr. Gerald Fischbach, Director of
the National Institute of Neurological Disorders and Stroke.
I am accompanied by Dr. Allen Spiegel, Director of the National
Institute of Diabetes and Digestive and Kidney Diseases. We
are before you again to discuss one of the most exciting areas
of biomedical research: the enormous potential of human pluripotent
stem cells to treat and cure debilitating and deadly diseases.
Only two years ago, researchers discovered
and isolated these primordial cells -- whose existence in
humans had been theorized but never proven -- the precursors
of most of the other cells in the body. Their unique properties
of self-renewal and the ability to differentiate into the
full spectrum of other cell types make them ideal candidates
for repairing and replacing tissues and organs ravaged by
disease. New more effective treatments, and maybe even cures,
might be developed for juvenile-onset diabetes, Parkinson=s
Disease, spinal cord injury, ALS or Lou Gehrig=s
disease, Alzheimer=s
Disease and many other brain disorders. There is similar potential
for the treatment of cancer and heart disease. Virtually every
realm of medicine and human health might benefit from this
innovation. Stem cell research could alleviate a great deal
of human suffering.
Chairman Specter, you and Senator
Harkin, in particular, have encouraged the National Institutes
of Health (NIH) to invest our resources in stem cell research
in order to pursue its enormous opportunities. Patients who
are suffering from the most deadly and disabling diseases
have also asked that NIH fund this promising arena of research.
We believe that federal funding would encourage openness,
stimulate more discoveries and translate the promise of this
research into practical use more quickly, efficiently, and
effectively B
and with procedural safeguards.
Recognizing that the ethical issues
related to this research required careful consideration, NIH
and the Department of Health and Human Services were committed
to developing Guidelines to help ensure that pluripotent
stem cell research funded by NIH would be conducted in a legal
and ethical manner. In drafting the Guidelines, the
NIH sought the advice of scientists, patients and patient
advocates, ethicists, clinicians, lawyers, the National Bioethics
Advisory Commission, and members of Congress. Draft Guidelines
were published in the Federal Register last December.
The NIH reviewed and considered all comments in preparing
the final Guidelines.
We are pleased to inform you that,
on August 25, NIH published final Guidelines for research
using human pluripotent stem cells. NIH is prepared to begin
receiving applications immediately. As soon as the oversight
process is in place, NIH will be in a position to fund such
research. We expect broad interest from researchers seeking
funding for pluripotent stem cell research, and we are hoping
to begin funding this research as soon as possible. For procedural
reasons, the soonest that awards could likely be made is early
next year.
What are stem cells?
Human pluripotent stem cells are a
unique scientific and medical resource. They can develop into
most of the specialized cells and tissues of the body, such
as muscle cells, nerve cells, liver cells, and blood cells,
and they are self-renewing, making them readily available
for research, and potentially, for treatment purposes. Scientists
derived these unique cells from human embryos and from fetal
tissue.
Why are human pluripotent stem cells
important?
There are three reasons why the isolation
of human pluripotent stem cells is so important to science
and the future of public health. First, pluripotent stem cells
could help us to understand the complex events that occur
during human development. Second, 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, and ensure
that only the safest drugs are tested in humans.
Third, and perhaps the most far-reaching
potential application of human pluripotent stem cells, the
generation of cells and tissue could be used for Acell
transplantation therapies.@
Such therapies are aimed at diseases and disorders resulting
from the destruction or dysfunction of specific cells and
tissue. Although donated organs and tissues can sometimes
be used to replace diseased or destroyed tissue, the number
of people suffering from such disorders far outstrips the
number of organs and tissues available for transplantation.
Pluripotent stem cells, stimulated to develop into specialized
cells and tissue, offer real hope for the possibility of a
renewable source of replacement cells and tissue to treat
a myriad of diseases, conditions, and disabilities for which
replacement tissue is in short supply. Examples of these include
neurological disorders (including spinal cord injuries and
ALS), diabetes, burns, heart disease, and arthritis.
Requirements of the Guidelines
The Guidelines prescribe procedures
to ensure that NIH-funded research in this important arena
is conducted in an ethical and legal manner. They specify
the documentation and assurances that must accompany requests
for NIH funding for research utilizing human pluripotent stem
cells. These Guidelines will encourage openness, help
make certain that researchers can make use of these critical
research tools, and help assure public access to the practical
medical benefits of research using these cells. The Guidelines
accomplish these goals in the following ways.
First, the Guidelines help ensure
that embryos will not be created for the purpose of deriving
human pluripotent stem cells to be used in NIH-supported research.
Investigators seeking NIH funds are required to provide documentation
that the human pluripotent stem cells were derived from frozen
embryos that were created for the purpose of fertility treatment
and that were in excess of clinical need. They require a clear
separation between the fertility treatment and the decision
to donate embryos for this research. In addition, the donation
of the human embryos must be made without any restriction
regarding the individual who may be the ultimate recipient
of the cells for transplantation. Similarly, researchers wishing
to use human fetal tissue to derive stem cells must demonstrate
that they are in compliance with all applicable laws and regulations.
The Federal statute applicable to NIH-funded fetal tissue
transplantation research also includes provisions creating
a separation between the decision to terminate a pregnancy
and the decision to donate fetal tissue for research.
Second, the Guidelines ensure
that individual choosing to donate embryos cannot receive
any inducements, monetary or otherwise. The Guidelines
detail specific elements that must be included in the informed
consent to help ensure that potential donors receive sufficient
information to allow them to decide whether or not to donate
human embryos for this type of research. The Guidelines
require review and approval by an Institutional Review Board
(IRB) to ensure that consent was informed, voluntary, and
meaningful.
Third, the Guidelines require
accountability on the part of the researcher. Detailed documentation
must be submitted to NIH to demonstrate compliance. For example,
the grantee institution must sign an assurance that the research
to be conducted is in compliance with the Guidelines,
and that the institution will maintain documentation to support
the assurance. The researcher/grantee institution must submit
a sample informed consent document, with patient identifier
information removed, a description of the informed consent
process, and documentation of IRB review.
Fourth, the Guidelines specify
types of research that the NIH will not fund. For example,
NIH will not fund any research that seeks to derive pluripotent
stem cells from human embryos, research utilizing pluripotent
stem cells that were derived from human embryos created for
research purposes, or any research that seeks to derive or
utilize stem cells from embryos that were created using somatic
cell nuclear transfer (cloning technology).
Fifth, the NIH has designed an oversight
process that will provide an extra level of protection, above
and beyond standard peer review of grant applications, to
ensure that researchers have complied with the Guidelines.
A newly-created NIH working group called the Human Pluripotent
Stem Cell Review Group (HPSCRG) will review documentation
submitted by researchers demonstrating that they are in compliance
with the Guidelines. Members of the HPSCRG will subsequently
make recommendations to its parent committee, the Center for
Scientific Review Advisory Committee. NIH will not fund research
or allow existing funds to be used for research using human
pluripotent stem cells derived from human embryos or human
fetal tissue until the required compliance documentation receives
HPSCRG review and approval of the NIH Center for Scientific
Review Advisory Committee.
Continued compliance with the Guidelines will be a
term and condition of the NIH award.
Human Pluripotent Stem Cells and
Diabetes Research
One of the best examples of the promise
of this line of research is in the treatment of Type 1 diabetes.
Research on islet cell transplantation and stem-cell biology
offers compelling opportunities for the development of new,
innovative approaches for treating and ultimately curing this
disease.
Type 1 diabetes, often referred to
as juvenile diabetes, is characterized by the inability of
the body to produce insulin, a hormone necessary for glucose
metabolism. This form of diabetes occurs when the body=s
immune system attacks and destroys its own insulin-producing
islet cells in the pancreas. As a result of inadequate insulin
production, glucose does not enter cells as readily as when
insulin levels are normal. The standard treatment is to try
to control the glucose level with insulin injections.
Transplantation of insulin-producing
islet cells is an alternative approach to controlling glucose
levels. In a recent study, seven patients receiving islet
transplants became completely independent of the need for
insulin injections. NIH is currently funding a multi-center
trial of the protocol used in this study to determine if the
same success can be achieved in a larger number of patients.
A successful outcome to this trial, as exciting as it would
be for patients with Type 1 diabetes, will only serve to underscore
the limitation in the supply of islets available for transplantation
compared to demand. While many approaches to address the islet
supply problem, including work on cell bioengineering and
adult stem cells are being vigorously pursued, human pluripotent
stem cells offer the greatest promise of providing a limitless
source of islet cells for treating and curing Type 1 diabetes.
Human Pluripotent Stem Cell Research
and the Nervous System
As significant as the promise of stem
cells is for the treatment of diabetes, the potential of stem
cells for treating diseases of the nervous system is equally
impressive. The most obvious and exciting use of stem cells
in neurological disorders is to replace nerve cells lost to
disease or injury. Many diseases destroy particular types
of nerve cells, and mature nerve cells cannot produce new
cells to replace those that are lost. Animal experiments have
demonstrated that the potential exists for coaxing stem cells
to specialize and replace the dopamine cells that are lost
in the brain through Parkinson=s
disease. A similar approach might also apply to several other
neurological disorders. Human pluripotent stem cells, given
appropriate control signals, might specialize to replace the
lost acetylcholine producing nerve cells in Alzheimer=s
disease, to restore lost motor neurons in ALS, or to produce
inhibitory cells to help restrain electrical activity in epilepsy.
Replacing lost nerve cells is only
the beginning of the list of possible therapeutic applications
for stem cells. For some disorders, such as multiple sclerosis,
stem cells might replace supporting cells, such as the glial
cells, which provide the insulation necessary to allow some
nerves to conduct electrical impulses rapidly. In addition
to their potential in replacement therapy, stem cells can
provided nutritive factors that might prevent the loss of
nerve cells in the first place. Stem cell strategies might
be useful for correcting inherited defects. For example, in
disorders that devastate children=s
brains, we might rely on the ability of stem cells to migrate
widely in the brain and supply the vital missing enzyme that
leads to early and tragic death from Tay-Sach=s
disease. In addition, stem cells might regenerate the many
different kinds of complex brain tissue that are damaged as
a result of brain trauma or stroke. Transplanted stem cells
might also supply natural growth and survival chemicals to
pave the way for regeneration of remaining healthy neural
tissue following spinal cord injury. Recent findings suggest
that stem cells might be harnessed to seek out and destroy
brain tumor cells that evade surgery or radiotherapy. The
list of possible applications of stem cells continues to grow
as we learn more about these cells.
Conclusion
Mr. Chairman, we appreciate the opportunity
to discuss this promising and extraordinary science and are
pleased to respond to any questions you may have.
DEPARTMENT OF HEALTH
& HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
NIH FACT SHEET ON HUMAN PLURIPOTENT STEM CELL RESEARCH GUIDELINES
Embargoed until 9
a.m., August 23, 2000
The Promise of Stem Cell Research
Human pluripotent stem cells are a
unique scientific and medical resource. They can develop into
most of the specialized cells and tissues of the body, such
as muscle cells, nerve cells, liver cells, and blood cells
and they can divide for indefinite periods in the laboratory,
making them readily available for research, and potentially,
treatment purposes. Scientists derived these unique cells
from human embryos and from non-living fetuses.
The establishment of human pluripotent
stem cell lines represents a major step forward in the understanding
of human biology. These unique cells have captured the interest
of scientists and the public, particularly patients and their
advocates. Although such research promises new treatments
and, possibly even cures for many debilitating diseases and
injuries, including Parkinson=s
disease, diabetes, heart disease, multiple sclerosis, burns
and spinal cord injuries, the National Institutes of Health
(NIH) acknowledges that the ethical issues related to this
research need due consideration.
The Need for Guidelines to
Govern Research Using Pluripotent Stem Cells
Federal law currently restricts the
use of Department of Health and Human Services (DHHS) funds
for human embryo research. DHHS funds cannot be used for the
derivation of stem cells from human embryos. The Congressional
restriction, however, does not prohibit funding for research
utilizing human pluripotent stem cells because such cells
are not embryos.
The purpose of the NIH Guidelines
is to prescribe procedures to help ensure that NIH-funded
research in this area is conducted in an ethical and legal
manner. By issuing these Guidelines, the NIH aims to
enhance both the scientific and ethical oversight of this
important arena of research and the pace at which scientists
can explore its many promises. These Guidelines will
encourage openness, help make certain that researchers can
make use of these critical research tools, and help assure
public access to the practical medical benefits of research
using these cells.
In an effort to help ensure that any
research utilizing human pluripotent stem cells is appropriately
and carefully conducted, the NIH sought the advice of scientists,
patients and patient advocates, ethicists, clinicians, lawyers,
the National Bioethics Advisory Commission (NBAC), members
of Congress, among others in drafting these Guidelines.
The draft Guidelines were published for public comment
in the Federal Register and after reviewing and considering
all comments, the NIH published the final NIH Guidelines
in the Federal Register on August 25, 2000.
Specifics of the Guidelines
The Guidelines prescribe the
documentation and assurances that must accompany requests
for NIH funding for research using human pluripotent stem
cells derived from human embryos or fetal tissue.
For studies using cells derived from human embryos, NIH
funds may be used only if the cells were derived from frozen
embryos that were created for the purposes of fertility
treatment and were in excess of clinical need.
The Guidelines prohibit the use of inducements,
monetary or otherwise, for the donation of the embryo. There
must also have been a clear separation between the fertility
treatment and the decision to donate embryos for this research.
Investigators
who propose to use human pluripotent stem cells from fetal
tissue will be expected to follow both the Guidelines
and all laws and regulations governing human fetal tissue
and human fetal tissue transplantation research.
The
Guidelines require that the informed consent specify
whether or not information that could identify the donor(s)
will be retained.
They
require that the donation of human embryos or fetal tissue
be made without any restriction regarding the individual(s)
who may be the recipient of the cells derived from the human
pluripotent stem cells for transplantation.
They
also require review and approval of the derivation protocol
by an Institutional Review Board (IRB).
The
informed consent should include statements that the embryos
or fetal tissue will be used to derive human pluripotent
stem cells for research, that may include human transplantation
research; that derived cells may be kept for many years;
that the research is not intended to provide direct medical
benefit to the donor; and, for cells derived from embryos,
that embryos donated will not be transferred to a woman=s
uterus and will not survive the stem cell derivation process.
The
informed consent must also state the possibility that the
results of the research may have commercial potential, and
that the donor will not receive any benefits from any such
future commercial development.
Areas of Research Ineligible for
NIH Funding
As required by law, NIH funds cannot
be used for the derivation of pluripotent stem cells from
human embryos. The Guidelines also set forth several
other areas of research that are ineligible for NIH funding,
including: 1) research in which human pluripotent stem cells
are utilized to create or contribute to a human embryo; 2)
research utilizing pluripotent stem cells that were derived
from human embryos created for research purposes; 3) research
in which human pluripotent stem cells are derived using somatic
cell nuclear transfer; 4) research utilizing human pluripotent
stem cells that were derived using somatic cell nuclear transfer;
5) research in which human pluripotent stem cells are combined
with an animal embryo; and 6) research in which human pluripotent
stem cells are derived using somatic cell nuclear transfer
for the purposes of reproductive cloning of a human.
Requirements for Investigators Applying
for Funds
A request for NIH funds for research
using these cells must include a signed assurance that the
cells were derived from human embryos in accordance with the
Guidelines and that the institution will maintain documentation
in support of the assurance.
This assurance must also affirm that:
The human pluripotent stem cells to be used in the research
were, or will be, obtained through a donation or through
a payment that does not exceed the reasonable costs associated
with the quality control, processing, transportation, preservation,
and storage of the stem cells.
The proposed research is not a class
of research that is ineligible for NIH funding.
Investigators must also submit:
A sample informed consent document, with patient identifier
information removed, and a description of the informed consent
process along with documentation of IRB approval of the
derivation protocol.
An abstract of the scientific protocol
used to derive human pluripotent stem cells along with a
title of the research proposal that proposes the use of
human pluripotent stem cells.
Ensuring Compliance with the Guidelines
Investigators requesting NIH funds
for research using pluripotent stem cells will need to provide
documentation that they are in compliance with the Guidelines
prior to receiving NIH funds for this class of research. Submitted
documentation will be reviewed by a newly-created NIH working
group called the Human Pluripotent Stem Cell Review Group
(HPSCRG).
Members of the working group will:
Review documentation of compliance with the Guidelines
for funding requests that propose the use of human pluripotent
stem cells
Advise the NIH Center for Scientific
Review Advisory Committee (CSRAC) of the outcome of their
review, which, if appropriate, will be approved by the CSRAC.
This decision will be forwarded to the funding Institute
or Center.
Hold
public meetings when a request proposes the use of a line
of human pluripotent stem cells that has not been previously
reviewed by the HPSCRG.
In no event will NIH fund research
or allow existing funds to be used for research using human
pluripotent stem cells derived from human embryos or human
fetal tissue until the derivation protocol has received HPSCRG
review and CSRAC approval.
Continued compliance with the Guidelines is a term
and condition of the NIH award.
Additional information about stem cells
can be found on the NIH Web site at www.nih.gov/news/stemcell/index.htm.
(The final Guidelines will be available on this site
as soon as they are released.)