[Federal Register Volume 64, Number 231 (Thursday, December 2, 1999)]
[Notices]
[Pages 67576-67579]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-31339]


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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: [email protected].

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:
     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.
     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.
     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]
BILLING CODE 4140-01-P