[Federal Register: December 2, 1999 (Volume 64, Number 231)]
[Notices]
[Page 67576-67579]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr02de99-43]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
National Institutes of Health
Draft National Institutes of Health Guidelines for Research
Involving Human Pluripotent Stem Cells (December 1999)
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SUMMARY: The National Institutes of Health (NIH) is requesting public
comment on a document entitled ``Draft National Institutes of Health
Guidelines for Research Involving Human Pluripotent Stem Cells
(December 1999).'' The purpose of these draft guidelines is to
recommend procedures to help ensure that NIH-funded research in this
area is conducted in an ethical and legal manner. The NIH will not fund
research using human pluripotent stem cells until final guidelines are
published in the Federal Register and an oversight process is in place.
DATES: Written comments should be received by NIH on or before January
31, 2000.
ADDRESSES: The NIH welcomes public comment on the Draft National
Institutes of Health Guidelines for Research Involving Human
Pluripotent Stem Cells (December 1999), set forth below.
Comments should be addressed to: Stem Cell Guidelines, NIH Office
of Science Policy, 1 Center Drive, Building 1, Room 218, Bethesda, MD
20892. Comments may also be sent by facsimile transmission to Stem Cell
Guidelines at (301) 402-0280, or by e-mail to: stemcell@mail.nih.gov.
SUPPLEMENTARY INFORMATION: In December 1998, two different groups of
scientists reported the successful isolation and culturing of human
pluripotent stem cells. Such cells have the ability to develop into
most of the specialized cells or tissues in the human body and can
divide for indefinite periods in culture. Because of the regenerative
capacity of pluripotent stem cells, a single culture of human
pluripotent stem cells could supply numerous researchers.
Establishment of human pluripotent stem cell lines represents a
major step forward in human biology and has generated much interest
among scientists and the public, particularly among patients and their
advocates, especially with regard to the ethical issues related to this
research.
Because these cells can give rise to many different types of cells,
such as muscle cells, nerve cells, heart cells, blood cells, and
others, they are enormously important to science and hold great promise
for advances in health care. For example, further research using human
pluripotent stem cells may help scientists:
<bullet> Generate cells and tissue that could be used for
transplantation. If human pluripotent stem cells can be stimulated to
develop into many different specialized cells of the body, the
resulting cells may someday be used as replacement cells and tissue to
treat many diseases and conditions including Parkinson's disease,
spinal cord injury, stroke, burns, heart disease, diabetes, and
arthritis.
<bullet> Improve our understanding of the complex events that occur
during normal human development and also help us understand what goes
wrong to cause diseases and conditions such as birth defects and
cancer.
<bullet> Change the way we develop drugs and test them for safety
and potential efficacy. New medications could initially be tested using
human pluripotent stem cells, such as liver cells or skin cells; only
the drugs that are both safe and appear to have a beneficial effect
would graduate to further testing, using laboratory animals and human
subjects.
Human pluripotent stem cells have been isolated using two different
methods. One group of scientists derived the pluripotent stem cells
from early-stage human embryos in excess of clinical need and donated
by people who were undergoing infertility treatment in an in vitro
fertilization (IVF) clinic. Another group of scientists derived the
pluripotent stem cells from human fetal tissue obtained from
pregnancies that had been terminated. In both cases, the individuals
gave informed consent for the embryos or fetal tissue to be used in
research. Neither research project utilized Department of Health and
Human Services (DHHS) funds but rather was funded by private sources.
Federal law currently prohibits DHHS from funding research in which
human embryos are created for research purposes or are destroyed,
discarded or subjected to greater than minimal risk. In light of this
legislative restriction, the Director of the National Institutes of
Health (NIH) sought a legal opinion from the DHHS Office of the General
Counsel on whether NIH funds may be used for research utilizing human
pluripotent stem cells.
DHHS concluded that the Congressional prohibition does not prohibit
the funding of research utilizing human pluripotent stem cells because
such cells are not embryos. Thus, NIH funding for research using
pluripotent stem cells derived from human embryos is not legislatively
prohibited. The legal opinion also clarified that human pluripotent
stem cells derived from fetal tissue would fall within the legal
definition of human fetal tissue and are, therefore, subject to federal
restrictions on the use of such tissue. NIH funding for research to
derive or utilize human pluripotent stem cells from fetal tissue is
permissible, subject to applicable law and regulation.
In view of the scientific and medical benefits that may result from
research using human pluripotent stem cells, it is essential that the
federal government play a role in funding and overseeing the conduct of
this research. Federal funding will make it possible for scientists--
both privately and federally funded--to have the opportunity to
[[Page 67577]]
pursue this important line of research. Federal funding will provide
oversight and direction that would be lacking if this research were the
sole province of private sources of funding and will also help ensure
that the results of research will be accessible to the public.
The NIH understands and respects the ethical, legal, and social
issues relevant to human pluripotent stem cell research and is
sensitive to the need to subject it to oversight more stringent than
that associated with the traditional NIH scientific peer review
process. In light of these issues, the NIH plans to move forward in a
careful and deliberate way, prior to funding any research utilizing
human pluripotent stem cells.
In an effort to ensure that any research utilizing human
pluripotent stem cells is conducted appropriately, the NIH Director
convened a Working Group of the Advisory Committee to the Director, NIH
(ACD) to advise the ACD on guidelines and oversight for research
involving human pluripotent stem cells. Specifically, the NIH Director
charged the Working Group with developing appropriate guidelines
governing research involving the derivation and use of human
pluripotent stem cells from fetal tissue and research involving the use
of human pluripotent stem cells derived from early human embryos in
excess of clinical need. In an effort to ensure that a broad spectrum
of viewpoints was considered, the working group was made up of
individuals with varied expertise and experience, among them basic and
clinical scientists, ethicists, lawyers, clinicians, as well as
patients and patient advocates. On April 8, 1999, the working group
held a public meeting to discuss draft guidelines. During the meeting,
time was set aside for public comment; several groups came forward to
speak, including the American Society of Cell Biology, the National
Conference of Catholic Bishops; the Society for Developmental Biology,
the Alliance for Aging Research, and the House Pro-Life Caucus. The
Executive Director of the National Bioethics Advisory Commission (NBAC)
also presented comments reflecting the status of the deliberations of
the NBAC at that time.
The text of the draft guidelines follows.
Draft National Institutes of Health Guidelines for Research
Involving Human Pluripotent Stem Cells (December 1999)
I. Scope of Guidelines
These guidelines apply to research applications or proposals for
National Institutes of Health (NIH) funding or support involving: (1)
Utilization of human pluripotent stem cells (also known as human
embryonic stem cells) derived (without Department of Health and Human
Services [DHHS] funding) from early human embryos, and (2) the
derivation or utilization of human pluripotent stem cells from fetal
tissue. For purposes of these guidelines, human pluripotent stem cells
are cells derived from early human embryos or fetal tissue that can
divide for indefinite periods in culture without specializing and have
the potential to develop into all of the three major tissue types. NIH
research funded under these guidelines will involve only human
pluripotent stem cells derived either from fetal tissue or from early
human embryos that are the products of in vitro fertilization in excess
of clinical need, that are not implanted in a woman's uterus and that
have not reached the stage when the first major tissue type is formed.
The DHHS is prohibited by appropriations law (Pub. L. 105-277,
section 511,112 STAT. 2681-386) from using any appropriated funds ``for
the creation of a human embryo or embryos for research purposes; or
research in which a human embryo or embryos are destroyed, discarded or
knowingly subjected to risk of injury or death. . . .'' The NIH asked
the General Counsel of DHHS to clarify whether research utilizing human
pluripotent stem cells is permissible under existing laws governing
human embryo and fetal tissue research. After careful consideration,
the DHHS concluded that, because these cells are not embryos, current
law does not prohibit the use of NIH funds for research utilizing human
pluripotent stem cells. In addition, it was determined that, to the
extent such cells are considered human fetal tissue, they are subject
to the federal requirements for fetal tissue research.
These guidelines prescribe conditions that should be met before NIH
funds are used to support research involving the utilization of human
pluripotent stem cells derived from early human embryos or the
derivation or utilization of human pluripotent stem cells from fetal
tissue. DHHS funds may not be used for the derivation of human
pluripotent stem cells from early human embryos. The guidelines also
designate certain areas of human pluripotent stem cell research as
ineligible for NIH funding.
II. Guidelines for Research Involving Human Pluripotent Stem Cells That
Is Eligible for NIH Funding
A. The Utilization of Human Pluripotent Stem Cells Derived From Early
Human Embryos
1. Considerations for the Utilization of Human Pluripotent Stem Cells
Derived From Early Human Embryos
Studies utilizing pluripotent stem cells derived from early human
embryos may be conducted using NIH funds only if the cells were derived
from early human embryos that were created for the purposes of
infertility treatment and were in excess of clinical need of the
individuals seeking such treatment.
a. It is essential that the donation of early human embryos in
excess of clinical need is voluntary. No inducements, monetary or
otherwise, should have been offered for the donation of early human
embryos for research purposes. Infertility clinics and/or their
affiliated laboratories should have implemented specific written
policies and practices to ensure that no such inducements are made
available.
b. There should have been a clear separation between the decision
to create embryos for infertility treatment and the decision to donate
early human embryos in excess of clinical need for research purposes.
Decisions related to the creation of embryos for infertility treatment
should have been made free from the influence of researchers or
investigators proposing to derive or utilize human pluripotent stem
cells in research. To avoid possible conflicts of interest, the
attending physician responsible for the fertility treatment and the
researcher or investigator deriving and/or proposing to utilize human
pluripotent stem cells should not have been one and the same person.
c. To ensure that early human embryos donated for research are in
excess of clinical need of the individuals seeking infertility
treatment and to allow potential donors time between the creation of
the embryos for infertility treatment and the decision to donate for
research purposes, only frozen early human embryos should have been
used to derive human pluripotent stem cells. In addition, individuals
undergoing infertility treatment should have been approached about
donation of early human embryos for the derivation of pluripotent stem
cells only at the time of deciding the disposition of embryos in excess
of clinical need.
d. Prior to the derivation of human pluripotent stem cells for use
in NIH-
[[Page 67578]]
supported research, all identifiers associated with the early human
embryos should have been removed.
e. Donation of early human embryos should have been made without
any restriction regarding the individual(s) who may be the recipients
of transplantation of the cells derived from the human pluripotent stem
cells.
2. Informed Consent Requirements for the Utilization of Human
Pluripotent Stem Cells Derived From Early Human Embryos
Informed consent should have been obtained from individuals who
have sought infertility treatment who elect to donate early human
embryos in excess of clinical need for research purposes. The informed
consent process should have included discussion of the following
information with potential donors, pertinent to making the decision
whether to donate their embryos for research purposes.
a. Informed consent should have included:
(i) A statement that the early human embryos will be used to derive
human pluripotent stem cells for research, that the human pluripotent
stem cells will be derived and used following these NIH guidelines, and
that the cells may be used, at some future time, for human
transplantation research.
(ii) A statement that all identifiers associated with the embryos
will be removed prior to the derivation of human pluripotent stem
cells.
(iii) A statement that donors will not receive any information
regarding subsequent testing on the embryo or the derived human
pluripotent cells.
(iv) A statement that derived cells and/or cell lines, with all
identifiers removed, may be kept for many years.
(v) Disclosure of the possibility that the donated material may
have commercial potential, and a statement that the donor will not
receive financial or any other benefits from any such future commercial
development.
(vi) A statement that the human pluripotent stem cell research is
not intended to provide direct medical benefit to the donor.
(vii) A statement that early human embryos donated will not be
transferred to a woman's uterus, will not survive the human pluripotent
stem cell derivation process, and will be handled respectfully, as is
appropriate for all human tissue used in research.
b. To ensure respect for the individuals donating early human
embryo(s), protocols should have been approved by an Institutional
Review Board (IRB) established in accord with 45 CFR Sec. 46.107 and
Sec. 46.108 or FDA regulations at 21 CFR Sec. 56.107 and Sec. 56.108.
3. Investigators Planning To Utilize Human Pluripotent Stem Cells
Derived From Early Human Embryos Should Provide in Their Application or
Proposal to NIH
a. documentation that the embryos were created for the purpose of
infertility treatment;
b. documentation that the early human embryos were frozen and in
excess of clinical need;
c. the protocol, including the informed consent document, used for
the derivation of human pluripotent stem cells from early human
embryos;
d. documentation of IRB approval of the research protocol; and
e. an assurance that the 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 transportation,
processing, preservation, quality control and storage of the stem
cells.
B. Derivation and Utilization of Human Pluripotent Stem Cells From
Fetal Tissue
1. Considerations for the Derivation and Utilization of Human
Pluripotent Stem Cells Derived From Fetal Tissue
Unlike pluripotent stem cells derived from early human embryos,
DHHS funds may be used to support research to derive pluripotent stem
cells from fetal tissue, as well as for research utilizing such cells.
Such research is governed by federal statutory restrictions regarding
fetal tissue research at 42 U.S.C. 289g-2(a) and the federal
regulations at 45 CFR 46.210. In addition, because cells derived from
fetal tissue at the early stages of investigation may at a later date
be utilized in human fetal tissue transplantation research, it is the
policy of NIH to require that all DHHS funded research involving the
derivation or utilization of pluripotent stem cells from fetal tissue
also comply with the fetal tissue transplantation research statute at
42 U.S.C. 289g-1.
2. Informed Consent Requirements for the Derivation and Utilization of
Human Pluripotent Stem Cells From Fetal Tissue
As a policy matter, NIH funded research deriving or utilizing human
pluripotent stem cells from fetal tissue should comply with the
informed consent law applicable to fetal tissue transplantation
research (42 U.S.C. 289g-1) and the following conditions. The informed
consent process should include discussion of the following information
with potential donors, pertinent to making the decision whether to
donate their embryos for research purposes.
a. Informed consent should include:
(i) A statement that the fetal tissue will be used to derive human
pluripotent stem cells for research, that the human pluripotent stem
cells will be derived and used following these NIH guidelines, and that
the cells may be used, at some future time, for transplantation
research.
(ii) A statement that all identifiers associated with the fetal
tissue will be removed prior to the derivation of human pluripotent
stem cells.
(iii) A statement that donors will not receive any information
regarding subsequent testing on the fetal tissue or the derived human
pluripotent cells.
(iv) A statement that derived cells and/or cell lines, with all
identifiers removed, may be kept for many years.
(v) Disclosure of the possibility that the donated material may
have commercial potential, and a statement that the donor will not
receive financial or any other benefits from any such future commercial
development.
(vi) A statement that the human pluripotent stem cell research is
not intended to provide direct medical benefit to the donor.
(vii) A statement that the fetal tissue and cells will be handled
respectfully, as is appropriate for all human tissue used in research.
b. To ensure respect for the individual donating tissue that
results from the reproductive process, it is recommended that protocols
be approved by an Institutional Review Board (IRB) established in
accord with 45 CFR 46.107 and Sec. 46.108 or FDA regulations at 21 CFR
56.107 and Sec. 56.108.
3. Investigators Planning To Derive or Utilize Human Pluripotent Stem
Cells From Fetal Tissue Should Provide in Their Application or Proposal
to NIH
a. the protocol, including the informed consent document, for the
derivation of human pluripotent stem cells from fetal tissue;
b. documentation of IRB approval, if any, of the research protocol;
and
c. an assurance that the 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 transportation,
processing, preservation, quality control and storage of the stem
cells, as permitted by 42 U.S.C. 289g-2.
[[Page 67579]]
III. Areas of Research Involving Human Pluripotent Stem Cells That Are
Ineligible for NIH Funding
Areas of research ineligible for NIH funding include:
A. The derivation of pluripotent stem cells from early human
embryos;
B. Research in which human pluripotent stem cells are utilized to
create or contribute to a human embryo;
C. Research in which human pluripotent stem cells are combined with
an animal embryo;
D. Research in which human pluripotent stem cells are used for
reproductive cloning of a human;
E. Research in which human pluripotent stem cells are derived using
somatic cell nuclear transfer, i.e., the transfer of a human somatic
cell nucleus into a human or animal egg;
F. Research utilizing human pluripotent stem cells that were
derived using somatic cell nuclear transfer, i.e., the transfer of a
human somatic cell nucleus into a human or animal egg; and
G. Research utilizing pluripotent stem cells that were derived from
human embryos created for research purposes, rather than for
infertility treatment.
IV. Oversight
A. Requests to the NIH for the funding of research involving human
pluripotent stem cells should include documentation that the human
pluripotent stem cells have been or will be derived in accordance with
these Guidelines.
B. NIH will consider requests for funding for research utilizing
human pluripotent stem cells from: (1) Awardees who want to use
existing funds; (2) awardees requesting an administrative supplement;
and (3) applicants or intramural researchers submitting applications or
proposals.
C. NIH will consider funding requests for the derivation of human
pluripotent stem cells from fetal tissue.
D. All applications shall be reviewed for scientific merit by: (1)
An initial review group, in the case of new or competing continuation
(renewal) applications; (2) by Institute or Center staff in the case of
requests to use existing funds or applications for an administrative
supplement; or (3) by the Scientific Director in the case of intramural
proposals prior to submission to the HPSCRG.
E. The NIH will establish a Human Pluripotent Stem Cell Review
Group (HPSCRG). This group will review documentation of compliance with
the NIH Guidelines for Research Involving Human Pluripotent Stem Cells,
and may, when warranted, seek further information in support of an
application. The group will hold public review meetings when a funding
request proposes the use of a newly derived line of human pluripotent
stem cells that has not been reviewed previously by the HPSCRG in a
public process or when an investigator proposes a protocol for the
derivation of a new human pluripotent stem cell line from fetal tissue.
F. The HPSCRG will compile a yearly report that will include the
number of applications and proposals reviewed and the titles of all
awarded applications, supplements or administrative approvals for the
use of existing funds, and intramural projects.
G. The HPSCRG will also serve as a resource for recommending to the
Director, NIH any revisions to the NIH Guidelines for Research
Involving Human Pluripotent Stem Cells.
Dated: November 29, 1999.
Harold Varmus,
Director, NIH.
[FR Doc. 99-31339 Filed 12-1-99; 8:45 am]
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