The National Bioethics Advisory Commission (NBAC) was established by Executive Order 12975,

signed by President Clinton on October 3, 1995. NBAC’s functions are defined as follows: 

a) NBAC shall provide advice and make recommendations to the National Science and Technology

Council and to other appropriate government entities regarding the following matters: 

1) the appropriateness of departmental, agency, or other governmental programs, policies,

assignments, missions, guidelines, and regulations as they relate to bioethical issues arising

from research on human biology and behavior; and

2) applications, including the clinical applications, of that research.

b) NBAC shall identify broad principles to govern the ethical conduct of research, citing specific

projects only as illustrations for such principles. 

c) NBAC shall not be responsible for the review and approval of specific projects. 

d) In addition to responding to requests for advice and recommendations from the National Science

and Technology Council, NBAC also may accept suggestions of issues for consideration from

both the Congress and the public. NBAC also may identify other bioethical issues for the

purpose of providing advice and recommendations, subject to the approval of the National

Science and Technology Council.

National Bioethics Advisory Commission

6100 Executive Boulevard, Suite 5B01, Rockville, Maryland 20892-7508

Telephone: 301-402-4242 • Fax: 301-480-6900 • Website: www.bioethics.gov
ETHICAL

ISSUES IN

HUMAN

STEM CELL

RESEARCH

VOLUME I

Report and 

Recommendations 

of the National 

Bioethics Advisory

Commission

Rockville, Maryland

September 1999

Table of Contents

Letter of Transmittal to the President

National Bioethics Advisory Commission

National Bioethics Advisory Commission Staff and Consultants

Executive Summary i

Chapter 1: Introduction 1

Introduction 1

Human Stem Cells: An Overview 1

Ethical Issues 2

Framework for This Report 3

Definitions Used in This Report 4

Organization of This Report 5

Notes 6

References 6

Chapter 2: Human Stem Cell Research and 

the Potential for Clinical Application 7

Introduction 7

Stem Cell Types 8

Animal Models 14

Human Models 16

Growth and Derivation of Embryonic Stem Cells 19

Potential Medical Applications of Human Embryonic Stem Cell 20

and Embryonic Germ Cell Research

Summary 23

Notes 24

References 24

Chapter 3: The Legal Framework for 

Federal Support of Research to 

Obtain and Use Human Stem Cells 29

Introduction 29

The Law Relating to Aborted Fetuses as Sources of 

Embryonic Germ Cells 29

The Law Relating to Embryos as Sources 

of Embryonic Stem Cells 33

The Law Relating to Deriving Stem Cells from Organisms 

Created Through Cloning 36

Summary 37

Notes 38

References 43

Chapter 4: Ethical Issues in 

Human Stem Cell Research 45

Ethical Issues Relating to the Sources

of Human Embryonic Stem or Embryonic Germ Cells 45

The Arguments Relating to Federal Funding 

of Research Involving the Derivation and/or 

Use of Embryonic Stem and Embryonic Germ Cells 57

Ethical Issues in Adopting Federal Oversight 

and Review Policies for Embryonic Stem and 

Embryonic Germ Cell Research 61

Summary 61

Notes 62

References 62

Chapter 5: Conclusions and Recommendations 65

Introduction 65

Scientific and Medical Considerations 65

Ethical and Policy Considerations 66

Conclusions and Recommendations 67

Summary 81

Notes 81

References 81

Appendices

Appendix A: Acknowledgments 83

Appendix B: Glossary 85

Appendix C: Letters of Request and Response 87

Appendix D: The Food and Drug Administration’s Statutory 

and Regulatory Authority to Regulate Human 

Stem Cells 93

Appendix E: Summary of Presentations on Religious 

Perspectives Relating to Research Involving 

Human Stem Cells, May 7, 1999 99

Appendix F: Points to Consider in Evaluating Basic Research

Involving Human Embryonic Stem Cells and

Embryonic Germ Cells 105

Appendix G: Public and Expert Testimony 109

Appendix H: Commissioned Papers 111




National Bioethics Advisory Commission

Patricia Backlar

Research Associate Professor of Bioethics

Department of Philosophy

Portland State University

Assistant Director

Center for Ethics in Health Care

Oregon Health Sciences University

Portland, Oregon

Arturo Brito, M.D.

Assistant Professor of Clinical Pediatrics

University of Miami School of Medicine

Miami, Florida

Alexander Morgan Capron, LL.B.

Henry W. Bruce Professor of Law

University Professor of Law and Medicine

Co-Director, Pacific Center for Health Policy and Ethics

University of Southern California

Los Angeles, California

Eric J. Cassell, M.D., M.A.C.P.

Clinical Professor of Public Health

Cornell University Medical College

New York, New York

R. Alta Charo, J.D.*

Professor of Law and Medical Ethics

Schools of Law and Medicine

The University of Wisconsin

Madison, Wisconsin

James F. Childress, Ph.D.

Kyle Professor of Religious Studies

Professor of Medical Education

Co-Director, Virginia Health Policy Center

Department of Religious Studies

The University of Virginia

Charlottesville, Virginia

David R. Cox, M.D., Ph.D.

Professor of Genetics and Pediatrics

Stanford University School of Medicine

Stanford, California

Rhetaugh Graves Dumas, Ph.D., R.N.

Vice Provost Emerita, Dean Emerita, and 

Lucille Cole Professor of Nursing

The University of Michigan

Ann Arbor, Michigan

Laurie M. Flynn

Executive Director

National Alliance for the Mentally Ill

Arlington, Virginia

Carol W. Greider, Ph.D.**

Professor of Molecular Biology and Genetics

Department of Molecular Biology and Genetics

The Johns Hopkins University School of Medicine

Baltimore, Maryland 

Steven H. Holtzman

Chief Business Officer

Millennium Pharmaceuticals Inc.

Cambridge, Massachusetts

Bette O. Kramer

Founding President

Richmond Bioethics Consortium

Richmond, Virginia

Bernard Lo, M.D.

Director

Program in Medical Ethics

The University of California, San Francisco

San Francisco, California

Lawrence H. Miike, M.D., J.D.

Kaneohe, Hawaii

Thomas H. Murray, Ph.D.

President

The Hastings Center

Garrison, New York

Diane Scott-Jones, Ph.D.

Professor

Department of Psychology

Temple University

Philadelphia, Pennsylvania

Harold T. Shapiro, Ph.D., Chair

President

Princeton University

Princeton, New Jersey

*To avoid the appearance of a conflict of interest, Commissioner Charo recused herself from all Commission deliberations as of February 1, 1999. 

She neither dissents from nor endorses this report and its recommendations.

**To avoid the appearance of a conflict of interest, Commissioner Greider recused herself from Commission deliberations as of July 19, 1999.

National Bioethics Advisory 

Commission Staff and Consultants

Executive Director

Eric M. Meslin, Ph.D.

Research Staff 

Kathi E. Hanna, M.S., Ph.D., Research Director

Emily C. Feinstein, Research Analyst*

Melissa Goldstein, J.D., Research Analyst*

E. Randolph Hull, Jr., Research Analyst*

J. Kyle Kinner, J.D., M.P.A., Presidential Management Intern

Kerry Jo Lee, Intern

Debra McCurry, M.S., Information Specialist

Daniel J. Powell, Intern

Andrew Siegel, Ph.D., J.D., Staff Philosopher**

Sean A. Simon, Research Analyst*

Robert Tanner, J.D., Research Analyst

Consultants

Burness Communications, Communications Consultant

Sara Davidson, M.A., Editor

Elisa Eiseman, Ph.D., Science Consultant

Jeffrey P. Kahn, Ph.D., M.P.H., Bioethics Consultant

Tamara Lee, Graphic Designer

LeRoy Walters, Ph.D., Bioethics Consultant

Administrative Staff

Jody Crank, Secretary to the Executive Director**

Evadne Hammett, Administrative Officer

Patricia Norris, Public Affairs Officer

Lisa Price, Secretary**

Margaret C. Quinlan, Office Manager

Sherrie Senior, Secretary

*Until May 1999

**Until July 1999

Executive Summary

Introduction

I

n November 1998, President Clinton charged the

National Bioethics Advisory Commission with the task

of conducting a thorough review of the issues associated

with human stem cell research, balancing all ethical and

medical considerations. The President’s request was

made in response to three separate reports that brought

to the fore the exciting scientific and clinical prospects of

stem cell research while also raising a series of ethical

controversies regarding federal sponsorship of scientific

inquiry in this area. Scientific reports of the successful

isolation and culture of these specialized cells have

offered hope of new cures for debilitating and even fatal

illness and at the same time have renewed an important

national debate about the ethics of research involving

human embryos and cadaveric fetal material.

Scientific and Medical Considerations

The stem cell is a unique and essential cell type found in

animals. Many kinds of stem cells are found in the body,

with some more differentiated, or committed, to a particular function than others. In other words, when stem

cells divide, some of the progeny mature into cells of a

specific type (e.g., heart, muscle, blood, or brain cells),

while others remain stem cells, ready to repair some of

the everyday wear and tear undergone by our bodies.

These stem cells are capable of continually reproducing

themselves and serve to renew tissue throughout an individual’s life. For example, they constantly regenerate the

lining of the gut, revitalize skin, and produce a whole

range of blood cells. Although the term stem cell

commonly is used to refer to the cells within the adult

organism that renew tissue (e.g., hematopoietic stem

cells, a type of cell found in the blood), the most fundamental and extraordinary of the stem cells are found in

the early stage embryo. These embryonic stem (ES) cells,

unlike the more differentiated adult stem cells or other

cell types, retain the special ability to develop into nearly

any cell type. Embryonic germ (EG) cells, which originate

from the primordial reproductive cells of the developing

fetus, have properties similar to ES cells. 

It is the potentially unique versatility of the ES and

EG cells derived, respectively, from the early stage

embryo and cadaveric fetal tissue that presents such

unusual scientific and therapeutic promise. Indeed, scientists have long recognized the possibility of using such

cells to generate more specialized cells or tissue, which

could allow the generation of new cells to be used to treat

injuries or diseases, such as Alzheimer’s disease,

Parkinson’s disease, heart disease, and kidney failure.

Likewise, scientists regard these cells as an important—

perhaps essential—means for understanding the earliest

stages of human development and as an important tool

in the development of life-saving drugs and cellreplacement therapies to treat disorders caused by early

cell death or impairment.

The techniques for deriving these cells have not been

fully developed as standardized and readily available

research tools, and the development of any therapeutic

application remains some years away. Thus, ES and EG

cells are still primarily a matter of intense research interest.

At this time, human stem cells can be derived from

the following sources:

■ human fetal tissue following elective abortion 

(EG cells),

i
ii

Executive Summary

■ human embryos that are created by in vitro fertilization (IVF) and that are no longer needed by couples

being treated for infertility (ES cells),

■ human embryos that are created by IVF with gametes

donated for the sole purpose of providing research

material (ES cells), and

■ potentially, human (or hybrid) embryos generated

asexually by somatic cell nuclear transfer or similar

cloning techniques in which the nucleus of an adult

human cell is introduced into an enucleated human

or animal ovum (ES cells).

In addition, although much promising research currently is being conducted with stem cells obtained from

adult organisms, studies in animals suggest that this

approach will be scientifically and technically limited,

and in some cases the anatomic source of the cells might

preclude easy or safe access. However, because there are

no legal restrictions or new ethical considerations

regarding research on adult stem cells (other than the

usual concerns about consent and risks), important

research can and should go forward in this area.

Moreover, because important biological differences exist

between embryonic and adult stem cells, this source of

stem cells should not be considered an alternative to ES

and EG cell research.

Ethical and Policy Considerations

The scientific reports of the successful isolation and culture of ES and EG cells have renewed a longstanding controversy about the ethics of research involving human

embryos and cadaveric fetal material. This controversy

arises from sharply differing moral views regarding elective abortion or the use of embryos for research. Indeed,

an earnest national and international debate continues

over the ethical, legal, and medical issues that arise in this

arena. This debate represents both a challenge and an

opportunity: a challenge because it concerns important

and morally contested questions regarding the beginning

of life, and an opportunity because it provides another

occasion for serious public discussion about important

ethical issues. We are hopeful that this dialogue will foster public understanding about the relationships between

the opportunities that biomedical science offers to

improve human welfare and the limits set by important

ethical obligations.

Although we believe most would agree that human

embryos deserve respect as a form of human life, disagreements arise regarding both what form such respect

should take and what level of protection is required at

different stages of embryonic development. Therefore,

embryo research that is not therapeutic to the embryo is

bound to raise serious concerns and to heighten the 

tensions between two important ethical commitments: to

cure disease and to protect human life. For those who

believe that the embryo has the moral status of a person

from the moment of conception, research (or any other

activity) that would destroy the embryo is considered

wrong and should not take place. For those who believe

otherwise, arriving at an ethically acceptable policy in

this arena involves a complex balancing of a number of

important ethical concerns. Although many of the issues

remain contested on moral grounds, they co-exist within

a broad area of consensus upon which public policy can,

at least in part, be constructed.

For most observers, the resolution of these ethical and

scientific issues depends to some degree on the source of

the stem cells. The use of cadaveric fetal tissue to derive

EG cell lines—like other uses of tissues or organs from

dead bodies—is generally the most accepted, provided

that the research complies with the system of public safeguards and oversight already in place for such scientific

inquiry. With respect to embryos and the ES cells from

which they can be derived, some draw an ethical distinction between two types of embryos. One is referred to as

the research embryo, an embryo created through IVF with

gametes provided solely for research purposes. Many

people, including the President, have expressed the view

that the federal government should not fund research

that involves creating such embryos. The second type of

embryo is that which was created for infertility treatment,

but is now intended to be discarded because it is unsuitable or no longer needed for such treatment. The use of

these embryos raises fewer ethical questions because it

does not alter their final disposition. Finally, the recent

demonstration of cloning techniques (somatic cell

nuclear transfer) in nonhuman animals suggests that

transfer of a human somatic cell nucleus into an oocyte
iii

National Bioethics Advisory Commission

might create an embryo that could be used as a source of

ES cells. The creation of a human organism using this

technique raises questions similar to those raised by the

creation of research embryos through IVF, and at this

time federal funds may not be used for such research. In

addition, if the enucleated oocyte that was to be combined

with a human somatic cell nucleus came from an animal

other than a human being, other issues would arise about

the nature of the embryo produced. Thus, each source of

material raises ethical questions as well as scientific,

medical, and legal ones.

Conscientious individuals have come to different conclusions regarding both public policy and private actions

in the area of stem cell research. Their differing perspectives by their very nature cannot easily be bridged by any

single public policy. But the development of public policy in a morally contested area is not a novel challenge for

a pluralistic democracy such as that which exists in the

United States. We are profoundly aware of the diverse

and strongly held views on the subject of this report and

have wrestled with the implications of these different

views at each of our meetings devoted to this topic. Our

aim throughout these deliberations has been to formulate

a set of recommendations that fully reflects widely shared

views and that, in our view, would serve the best interests

of society.

Most states place no legal restrictions on any of the

means of creating ES and EG cells that are described in

this report. In addition, current Food and Drug

Administration regulations do not apply to this type of

early stage research. Therefore, because the public controversy surrounding such activities in the United States

has revolved around whether it is appropriate for the 

federal government to sponsor such research, this report

focuses on the question of whether the scientific merit

and the substantial clinical promise of this research

justify federal support, and, if so, with what restrictions

and safeguards.

Conclusions and Recommendations

This report presents the conclusions that the

Commission has reached and the recommendations that

the Commission has made in the following areas: the

ethical acceptability of federal funding for research that

either derives or uses ES or EG cells; the means of

ensuring appropriate consent of women or couples

who donate cadaveric fetal tissue or embryos remaining after infertility treatments; the need for restrictions

on the sale of these materials and the designation of

those who may benefit from their use; the need for 

ethical oversight and review of such research at the

national and institutional level; and the appropriateness of voluntary compliance by the private sector with

some of these recommendations.

The Ethical Acceptability of Federal Funding 

of ES and EG Cell Research by the Source 

of the Material

A principal ethical justification for public sponsorship

of research with human ES or EG cells is that this

research has the potential to produce health benefits for

individuals who are suffering from serious and often fatal

diseases. We recognize that it is possible that the various

sources of human ES or EG cells eventually could be

important to research and clinical application because of,

for example, their differing proliferation potential, differing availability and accessibility, and differing ability to be

manipulated, as well as possibly significant differences in

their cell biology. At this time, therefore, the

Commission believes that federal funding for the use

and derivation of ES and EG cells should be limited

to two sources of such material: cadaveric fetal tissue

and embryos remaining after infertility treatments.

Specific recommendations and their justifications are

provided below.

Recommendation 1: EG Cells from Fetal Tissue

Research involving the derivation and use of

human EG cells from cadaveric fetal tissue should

continue to be eligible for federal funding.

Relevant statutes and regulations should be

amended to make clear that the ethical safeguards

that exist for fetal tissue transplantation also

apply to the derivation and use of human EG cells

for research purposes.

Considerable agreement exists, both in the United

States and throughout the world, that the use of fetal 

tissue in therapy for people with serious disorders, such
iv

Executive Summary

as Parkinson’s disease, is acceptable. Research that uses

tissue from aborted fetuses is analogous to the use of fetal

tissue in transplantation. The rationales for conducting

EG research are equally strong, and the arguments

against it are not persuasive. The removal of fetal germ

cells does not occasion the destruction of a live fetus, 

nor is fetal tissue intentionally or purposefully created 

for human stem cell research. Although abortion itself

doubtless will remain a contentious issue in our society,

the procedures that have been developed to prevent fetal

tissue donation for therapeutic transplantation from

influencing the abortion decision offer a model for creating such separation in research to derive human EG cells.

Because the existing statutes are written in terms of 

tissue transplantation, which is not a current feature of

EG cell research, changes are needed to make it explicit

that the relevant safeguards will apply to research to

derive EG cells from aborted fetuses. At present, no legal

prohibitions exist that would inhibit the use of such 

tissue for EG cell research.

Recommendation 2: ES Cells from Embryos

Remaining After Infertility Treatments

Research involving the derivation and use of

human ES cells from embryos remaining after

infertility treatments should be eligible for federal

funding. An exception should be made to the present statutory ban on federal funding of embryo

research to permit federal agencies to fund

research involving the derivation of human ES

cells from this source under appropriate regulations that include public oversight and review.

(See Recommendations 5 through 9.)

The current ban on embryo research is in the form of

a rider to the appropriations bill for the Department of

Health and Human Services (DHHS), of which the

National Institutes of Health (NIH) is a part. The rider

prohibits use of the appropriated funds to support any

research “in which a human embryo [is] destroyed, discarded, or knowingly subjected to risk of injury greater

than that allowed for research on fetuses in utero” (Pub.

L. No. 105-78, 513(a)). The term “human embryo” in the

statute is defined as “any organism . . . that is derived by

fertilization, parthenogenesis, cloning, or any other

means from one or more human gametes or human

diploid cells.” The ban is revisited each year when the

language of the NIH appropriations bill is considered.

The ban, which concerns only federally sponsored

research, reflects a moral point of view either that

embryos deserve the full protection of society because of

their moral status as persons or that there is sufficient

public controversy to preclude the use of federal funds

for this type of research. At the same time, however,

some effects of the embryo research ban raise serious

moral and public policy concerns for those who hold

differing views regarding the ethics of embryo research.

In our view, the ban conflicts with several of the ethical

goals of medicine and related health disciplines, especially healing, prevention, and research. These goals are

rightly characterized by the principles of beneficence

and nonmaleficence, which jointly encourage pursuing

social benefits and avoiding or ameliorating potential

harm.

Although some may view the derivation and use of

ES cells as ethically distinct activities, we do not believe

that these differences are significant from the point of

view of eligibility for federal funding. That is, we believe

that it is ethically acceptable for the federal government

to finance research that both derives cell lines from

embryos remaining after infertility treatments and that

uses those cell lines. Although one might argue that

some important research could proceed in the absence of

federal funding for research that derives stem cells from

embryos remaining after infertility treatments (i.e., federally funded scientists merely using cells derived with

private funds), we believe that it is important that federal

funding be made available for protocols that also derive

such cells. Relying on cell lines that might be derived

exclusively by a subset of privately funded researchers

who are interested in this area could severely limit 

scientific and clinical progress. 

Trying to separate research in which human ES cells

are used from the process of deriving those cells presents

an ethical problem, because doing so diminishes the scientific value of the activities receiving federal support.

This separation—under which neither biomedical

researchers at NIH nor scientists at universities and other

research institutions that rely on federal support could

participate in some aspects of this research—rests on the
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National Bioethics Advisory Commission

mistaken notion that the two areas of research are so 

distinct that participating in one need not mean participating in the other. We believe that this is a misrepresentation of the new field of human stem cell research,

and this misrepresentation could adversely affect scientific progress for several reasons.

First, researchers using human ES cell lines will

derive substantial scientific benefits from a detailed

understanding of the process of ES cell derivation,

because the properties of ES cells and the methods for

sustaining the cell lines may differ depending on the

conditions and methods that were used to derive them.

Thus, scientists who conduct basic research and are

interested in fundamental cellular processes are likely to

make elemental discoveries about the nature of ES cells

as they derive them in the laboratory. Second, significant

basic research needs to be conducted regarding the

process of ES cell derivation before cell-based therapies

can be realized, and this work must be pursued in a wide

variety of settings, including those exclusively devoted to

basic academic research. Third, ES cells are not indefinitely stable in culture. As these cells are grown, irreversible changes occur in their genetic makeup. Thus,

especially in the first few years of human ES cell research,

it is important to be able to repeatedly derive ES cells in

order to ensure that the properties of the cells that are

being studied have not changed.

Thus, anyone who believes that federal support of

this important new field of research should maximize its

scientific and clinical value within a system of appropriate ethical oversight should be dissatisfied with a position that allows federal agencies to fund research using

human ES cells but not research through which the cells

are derived from embryos. Instead, recognizing the close

connection in practical and ethical terms between derivation and use of the cells, it would be preferable to

enact provisions applicable to funding by all federal

agencies, provisions that would carve out a narrow

exception for funding of research to use or to derive

human ES cells from embryos that are being discarded

by infertility treatment programs.

Recommendation 3: ES Cells from Embryos Made

Solely for Research Purposes Using IVF

Federal agencies should not fund research involving

the derivation or use of human ES cells from embryos

made solely for research purposes using IVF.

ES cells can be obtained from human research

embryos created from donor gametes through IVF for the

sole purpose of deriving such cells for research. The primary objection to creating embryos specifically for

research is that there is a morally relevant difference

between generating an embryo for the sole purpose of

creating a child and producing an embryo with no such

goal. Those who object to creating embryos for research

often appeal to arguments about respecting human dignity by avoiding instrumental use of human embryos

(i.e., using embryos merely as a means to some other goal

does not treat them with appropriate respect or concern

as a form of human life). 

In 1994, the NIH Human Embryo Research Panel

argued in support of federal funding of the creation of

embryos for research purposes in exceptional cases, such

as the need to create banks of cell lines with different

genetic make-ups that encoded various transplantation

antigens—the better to respond, for example, to the

transplant needs of groups with different genetic profiles.

This would require the recruitment of embryos from

genetically diverse donors.

In determining how to deal with this issue, a number

of points are worth considering. First, it is possible that

the creation of research embryos will provide the only

way in which to conduct certain kinds of research, such

as research into the process of human fertilization.

Second, as IVF techniques improve, it is possible that the

supply of embryos for research from this source will

dwindle. Nevertheless, we have concluded that, either

from a scientific or a clinical perspective, there is no compelling reason at this time to provide federal funds for the

creation of embryos for research. At the current time,

cadaveric fetal tissue and embryos remaining after infertility treatment provide an adequate supply of research

resources for federal research projects.

Recommendation 4: ES Cells from Embryos Made

Using Somatic Cell Nuclear Transfer into Oocytes

Federal agencies should not fund research involving the derivation or use of human ES cells from

embryos made using somatic cell nuclear transfer

into oocytes.

Somatic cell nuclear transfer of the nucleus of an

adult somatic cell into an enucleated human egg likely
vi

Executive Summary

has the potential of creating a human embryo. To date,

although little is known about these embryos as potential

sources of human ES cells, there is significant reason to

believe that their use may have therapeutic potential. For

example, the potential use of matched tissue for autologous cell replacement therapy from ES cells may require

the use of somatic cell nuclear transfer. The use of this

technique to create an embryo arguably is different from

all the other cases we considered—due to the asexual

origin of the source of the ES cells—although oocyte

donation is necessarily involved. The Commission

concludes that, at this time, federal funding should not

be provided to derive ES cells from this source.

Nevertheless, scientific progress and the medical utility

of this line of research should be monitored closely. 

Requirements for the Donation of Cadaveric

Fetal Tissue and Embryos for Research 

Potential donors of embryos for ES cell research must

be able to make voluntary and informed choices about

whether and how to dispose of their embryos. Because of

concerns about coercion and exploitation of potential

donors, as well as societal controversy about the moral

status of embryos, it is important, whenever possible, to

separate donors’ decisions to dispose of their embryos

from their decisions to donate them for research.

Potential donors should be asked to provide embryos for

research only if they have decided to have those embryos

discarded instead of donating them to another couple or

storing them. If the decision to discard the embryos precedes the decision to donate them for research purposes,

then the research determines only how their destruction

occurs, not whether it occurs.

Recommendation 5: Requirements for Donation to

Stem Cell Research of Embryos That Would

Otherwise Be Discarded After Infertility Treatment

Prospective donors of embryos remaining after infertility treatments should receive timely, relevant, and

appropriate information to make informed and 

voluntary choices regarding disposition of the

embryos. Prior to considering the potential

research use of the embryos, a prospective donor

should have been presented with the option of

storing the embryos, donating them to another

woman, or discarding them. If a prospective donor

chooses to discard embryos remaining after 

infertility treatment, the option of donating to

research may then be presented. (At any point, the

prospective donors’ questions—including inquiries

about possible research use of any embryos remaining after infertility treatment—should be answered

truthfully, with all information that is relevant to

the questions presented.) 

During the presentation about potential research

use of embryos that would otherwise be discarded,

the person seeking the donation should

a) disclose that the ES cell research is not

intended to provide medical benefit to embryo

donors,

b) make clear that consenting or refusing to

donate embryos to research will not affect the

quality of any future care provided to prospective donors,

c) describe the general area of the research to be

carried out with the embryos and the specific

research protocol, if known,

d) disclose the source of funding and expected

commercial benefits of the research with the

embryos, if known,

e) make clear that embryos used in research will

not be transferred to any woman’s uterus, and

f) make clear that the research will involve the

destruction of the embryos.

To assure that inappropriate incentives do not enter

into a woman’s decision to have an abortion, we recommend that directed donation of cadaveric fetal tissue for

EG cell derivation be prohibited. Although the ethical

considerations supporting a prohibition of the directed

donation of human fetal tissue are less acute for EG cell

research than for transplantation, certain concerns

remain. Potential donors of cadaveric fetal tissue for EG

cell derivation would not receive a direct therapeutic

incentive to create or abort tissue for research purposes in

the same way that such personal interest might arise in a

transplant context. However, we agree that the prohibition remains a prudent and appropriate way of assuring

that inappropriate incentives, regardless of how remote

they may be, are not introduced into a woman’s decision

to have an abortion. Any suggestion of personal benefit

to the donor or to an individual known to the donor

would be untenable and possibly coercive.
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National Bioethics Advisory Commission

Recommendation 6: No Promises to Embryo Donors

That Stem Cells Will Be Provided to Particular

Patient-Subjects 

In federally funded research involving embryos

remaining after infertility treatments, researchers

may not promise donors that ES cells derived 

from their embryos will be used to treat patientsubjects specified by the donors.

Existing rules prohibit the practice of designated

donation, the provision of monetary inducements to

women undergoing abortion, and the purchase or sale of

fetal tissue. We concur in these restrictions and in the

earlier recommendation of the 1988 Human Fetal Tissue

Transplantation Research Panel that the sale of fetal tissue

for research purposes should not be permitted under any

circumstances. The potential for coercive pressure is

greatest when financial incentives are present, and the

treatment of the developing human embryo or fetus as an

entity deserving of respect may be greatly undermined by

the introduction of any commercial motive into the

donation or solicitation of fetal or embryonic tissue for

research purposes. 

Recommendation 7: Commerce in Embryos and

Cadaveric Fetal Tissue

Embryos and cadaveric fetal tissue should not be

bought or sold.

If and when sufficient scientific evidence and societal

agreement exist that the creation of embryos specifically

for research or therapeutic purposes is justified (specifically through somatic cell nuclear transfer), prohibitions

on directed donation should be revisited. For obvious

reasons, the use of somatic cell nuclear transfer to develop

ES cells for autologous transplantation might require

that the recipient be specified.

The Need for National Oversight and Review

The need for national as well as local oversight and

review of human stem cell research is crucial. No such

system currently exists in the United States. A national

mechanism to review protocols for deriving human ES

and EG cells and to monitor research using such cells

would ensure strict adherence to guidelines and standards

across the country. Thus, federal oversight can provide

the public with the assurance that research involving

stem cells is being undertaken appropriately. Given the

ethical issues involved in human stem cell research—

an area in which heightened sensitivity about the 

very research itself led the President to request that 

the Commission study the issue—the public and 

the Congress must be assured that oversight can be

accomplished efficiently, constructively, and in a timely

fashion, with sufficient attention to the relevant

ethical considerations.

Recommendation 8: Creation and Duties of an

Oversight and Review Panel 

DHHS should establish a National Stem Cell

Oversight and Review Panel to ensure that all federally funded research involving the derivation

and/or use of human ES or EG cells is conducted

in conformance with the ethical principles and

recommendations contained in this report. The

panel should have a broad, multidisciplinary

membership, including members of the general

public, and should

a) review protocols for the derivation of ES and

EG cells and approve those that meet the

requirements described in this report,

b) certify ES and EG cells lines that result from

approved protocols,

c) maintain a public registry of approved protocols and certified ES and EG cell lines,

d) establish a database—linked to the public 

registry—consisting of information submitted

by federal research sponsors (and, on a voluntary basis, by private sponsors, whose proprietary information shall be appropriately

protected) that includes all protocols that

derive or use ES or EG cells (including any

available data on research outcomes, including

published papers),

e) use the database and other appropriate sources

to track the history and ultimate use of certified cell lines as an aid to policy assessment

and formulation,

f) establish requirements for and provide guidance to sponsoring agencies on the social and

ethical issues that should be considered in the

review of research protocols that derive or use

ES or EG cells, and
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Executive Summary

g) report at least annually to the DHHS Secretary

with an assessment of the current state of the

science for both the derivation and use of

human ES and EG cells, a review of recent

developments in the broad category of stem

cell research, a summary of any emerging ethical or social concerns associated with this

research, and an analysis of the adequacy and

continued appropriateness of the recommendations contained in this report.

The Need for Local Review 

of Derivation Protocols

For more than two decades, prospective review by an

Institutional Review Board (IRB) has been the principal

method for assuring that federally sponsored research

involving human subjects will be conducted in compliance with guidelines, policies, and regulations designed

to protect human beings from harm. This system of local

review has been subject to criticism, and, indeed, in previous analyses we have identified a number of concerns

regarding this system. In the course of preparing this

report, we considered a number of proposals that would

allow for the local review of research protocols involving

human stem cell research, bearing in mind that a decision by the Commission to recommend a role for IRBs

might be incorrectly interpreted as endorsing the view

that human ES or EG cells or human embryos are human

subjects and therefore would be under the purview of the

Common Rule.

We adopted the principle, reflected in these recommendations, that for research to derive human ES and EG

cells, a system of national oversight and review supplemented by local review would be necessary to ensure that

important research could proceed—but only under specific conditions. We recognized that for research proposals involving the derivation of human ES or EG cells,

many of the ethical issues associated with these protocols

could be considered at the local level, that is, at the institutions at which the research would be taking place. For

protocols using but not deriving ES cells (i.e., generating

the cells elsewhere), a separate set of ethical deliberations

would have occurred. In general, the IRB is an appropriate body to review protocols that aim to derive ES or EG

cells. Although few review bodies (including IRBs) have

extensive experience in reviewing protocols of this kind,

they remain the most visible and expert entities available.

It is for this reason, for example, that we make a number

of recommendations (8, 9, 10, 11, and 12) that discuss

the importance of developing additional guidance for the

review of such protocols.

For proposals involving the derivation of human ES or

EG cells, particular sensitivities require attention through

a national review process. This process should, however,

begin at the local level, because institutions that intend to

conduct research involving the derivation of human ES

cells or EG cells should continue to take responsibility for

assuring the ethical conduct of that research. More importantly, however, IRBs can play an important role, particularly by reviewing consent documents and by assuring

that collaborative research undertaken by investigators at

foreign institutions has satisfied any regulatory requirements for sharing research materials.

Recommendation 9: Institutional Review of

Protocols to Derive Stem Cells

Protocols involving the derivation of human ES

and EG cells should be reviewed and approved by

an IRB or by another appropriately constituted

and convened institutional review body prior to

consideration by the National Stem Cell Oversight

and Review Panel. (See Recommendation 8.) This

review should ensure compliance with any

requirements established by the panel, including

confirming that individuals or organizations (in

the United States or abroad) that supply embryos

or cadaveric fetal tissue have obtained them in

accordance with the requirements established by

the panel.

Responsibilities of Federal Research Agencies

Federal research agencies have in place a comprehensive system for the submission, review, and approval of

research proposals. This system includes the use of a peer

review group—sometimes called a study section or initial

review group—that is established to assess the scientific

merit of the proposals. In addition, in some agencies,

such as NIH, staff members review protocols prior to

their transmittal to a national advisory council for final

approval. These levels of review provide an opportunity

to consider ethical issues that arise in the proposals.
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National Bioethics Advisory Commission

When research proposals involve human subjects, federal

agencies rely on local IRBs to review and approve the

research in order to assure that it is ethically acceptable.

(See Recommendation 9.) A grant application should not

be funded until ethical issues that are associated with

research involving human subjects have been resolved

fully. Therefore, at every point in this continuum—from

the first discussions that a prospective applicant may

have with program staff within a particular institution to

the final decision by the relevant national advisory

council—ethical and scientific issues can be addressed

by the sponsoring agency.

Recommendation 10: Sponsoring Agency Review of

Research Use of Stem Cells

All federal agencies should ensure that their

review processes for protocols using human ES or

EG cells comply with any requirements established by the National Stem Cell Oversight and

Review Panel (see Recommendation 8), paying

particular attention to the adequacy of the justification for using such cell lines.

Research involving human ES and EG cells raises critical ethical issues, particularly when the proposals

involve the derivation of ES cells from embryos remaining after infertility treatments. We recognize that these

research proposals may not follow the paradigm usually

associated with human subjects research. Nevertheless,

research proposals being considered for funding by federal agencies must, in our view, meet the highest standards of scientific merit and ethical acceptability. To that

end, the recommendations made in this report, including

a proposed set of Points to Consider in Evaluating Basic

Research Involving Human ES Cells and EG Cells, constitute

a set of ethical and policy considerations that should be

reflected in the respective policies of federal agencies

conducting or sponsoring human ES or EG cell research. 

Attention to Issues for the Private Sector

Although this report primarily addresses the ethical

issues associated with the use of federal funds for

research to derive and use ES and EG cells, we recognize

that considerable work in both of these areas will be conducted under private sponsorship. Thus, our recommendations may have implications for those working in the

private sector. First, for cell lines to be eligible for use in

federally funded research, they must be certified by the

National Stem Cell Oversight and Review Panel

described in Recommendation 8. Therefore, if a private

company aims to make its cell lines available to publicly

funded researchers, it must submit its derivation protocol(s) to the same oversight and review process recommended for the public sector, i.e., local review (see

Recommendation 9) and for certification that the cells

have been derived from embryos remaining after infertility treatments or from cadaveric fetal tissue.

Second, we hope that nonproprietary aspects of protocols developed under private sponsorship will be made

available in the public registry, as described in

Recommendation 8. The greater the participation of the

private sector in providing information on stem cell

research, the more comprehensive the development of

the science and related public policies in this area. 

Third, and perhaps most relevant, in an ethically sensitive area of emerging biomedical research it is important that all members of the research community,

whether in the public or private sectors, conduct the

research in a manner that is open to appropriate public

scrutiny. The last two decades have witnessed an

unprecedented level of cooperation between the public

and private sectors in biomedical research, which has

resulted in the international leadership position of the

United States in this arena. Public bodies and other

authorities, such as the Recombinant DNA Advisory

Committee, have played a crucial role in enabling important medical advances in fields such as gene therapy by

providing oversight of both publicly and privately funded

research efforts. We believe that voluntary participation

by the private sector in the review and certification procedures of the proposed national panel, as well as in its

deliberations, can contribute equally to the socially

responsible development of ES and EG cell technologies

and accelerate their translation into biomedically

important therapies that will benefit patients.

Recommendation 11: Voluntary Actions by Private

Sponsors of Research That Would Be Eligible for

Federal Funding

For privately funded research projects that involve

ES or EG cells that would be eligible for federal

funding, private sponsors and researchers are
x

Executive Summary

encouraged to adopt voluntarily the applicable

recommendations of this report. This includes

submitting protocols for the derivation of ES or

EG cells to the National Stem Cell Oversight and

Review Panel for review and cell line certification.

(See Recommendations 8 and 9.)

In this report, we recommend that federally funded

research to derive ES cells be limited to those efforts that

use embryos remaining after infertility treatment. Some of

the recommendations made in this context—such as the

requirement for separating the decision by a woman to

cease such treatment when embryos still remain and her

decision to donate those embryos to research—simply do

not apply to efforts to derive ES cells from embryos created (whether by IVF or somatic cell nuclear transfer)

solely for research purposes, activities that might be pursued in the private sector. Nevertheless, other ethical

standards and safeguards embodied in the recommendations, such as provisions to prevent the coercion of

women and the commodification of human reproduction, remain vitally important, even when embryos are

created solely for research purposes.

Recommendation 12: Voluntary Actions by Private

Sponsors of Research That Would Not Be Eligible

for Federal Funding

For privately funded research projects that involve

deriving ES cells from embryos created solely for

research purposes and that are therefore not eligible for federal funding (see Recommendations 3

and 4)

a) professional societies and trade associations

should develop and promulgate ethical safeguards and standards consistent with the principles underlying this report, and

b) private sponsors and researchers involved in

such research should voluntarily comply with

these safeguards and standards.

Professional societies and trade associations dedicated

to reproductive medicine and technology play a central

role in establishing policy and standards for clinical care,

research, and education. We believe that these organizations can and should play a salutary role in ensuring that

all stem cell and embryo research conducted in the

United States, including that which is privately funded,

conforms to the ethical principles underlying this report.

Many of these organizations already have developed 

policy statements, ethics guidelines, or other directives

addressing issues in this report, and the Commission has

benefited from a careful review of these materials. These

organizations are encouraged to review their professional

standards to ensure not only that they keep pace with the

evolving science of human ES and EG cell research, but

also that their members are knowledgeable about and in

compliance with them. For those organizations that 

conduct research in this area but that lack statements 

or guidelines addressing the topics of this report, we 

recommend strongly that they develop such statements

or guidelines. No single institution or organization,

whether in the public or the private sector, can provide

all the necessary protections and safeguards.

The Need for Ongoing Review and Assessment

No system of federal oversight and review of such a

sensitive and important area of investigation should be

established without simultaneously providing an evaluation of its effectiveness, value, and ongoing need. The

pace of scientific development in human ES and EG cell

research likely will increase. Although one cannot predict

the direction of the science of human stem cell research,

in order for the American public to realize the promise of

this research and to be assured that it is being conducted

responsibly, close attention to and monitoring of all the

mechanisms established for oversight and review are

required.

Recommendation 13: Sunset Provision for 

National Panel

The National Stem Cell Oversight and Review

Panel described in Recommendation 8 should be

chartered for a fixed period of time, not to exceed

five years. Prior to the expiration of this period,

DHHS should commission an independent evaluation of the panel’s activities to determine whether

it has adequately fulfilled its functions and

whether it should be continued.

There are several reasons for allowing the national

panel to function for a fixed period of time and for evaluating its activities before continuing. First, some of the

hoped-for results will be available from research projects
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National Bioethics Advisory Commission

that are using the two sources we consider to be ethically

acceptable for federal funding. Five years is a reasonable

period of time to allow some of this information to

amass, offering the panel, researchers, members of

Congress, and the public sufficient time to determine

whether any of the knowledge or potential health benefits are being realized. The growing body of information

in the public registry and database described above (particularly if privately funded researchers and sponsors

voluntarily participate) will aid these considerations.

Second, within this period the panel may be able to

determine whether additional sources of ES cells are necessary in order for important research to continue. Two

arguments are evident for supporting research using

embryos created specifically for research purposes: one is

the concern that not enough embryos remain for this

purpose from infertility treatments, and the other is the

recognition that some research requires embryos that are

generated particularly for research and/or medical purposes. The panel should assess whether additional

sources of ES cells that we have judged to be ineligible for

federal funding at this time (i.e., embryos created solely

for research purposes) are needed.

Third, an opportunity to assess the relationship

between local review of protocols using human ES and

EG cells and the panel’s review of protocols for the derivation of ES cells will be offered. It will, of course, take

time for this national oversight and review mechanism to

develop experience with the processes of review, certification, and approval described in this report. Fourth, we

hope that the panel will contribute to the national dialogue on the ethical issues regarding research involving

human embryos. A recurring theme of our deliberations,

and in the testimony we heard, was the importance of

encouraging this ongoing national conversation.

The criteria for determining whether the panel has

adequately fulfilled its functions should be set forth by an

independent body established by DHHS. However, it

would be reasonable to expect that the evaluation would

rely generally on the seven functions described above in

Recommendation 8 and that this evaluation would be

conducted by a group with expertise in these areas. In

addition, some of the following questions might be 

considered when conducting this evaluation: Is there reason to believe that the private sector is voluntarily submitting descriptions of protocols involving the derivation

of human ES cells to the panel for review? Is the panel

reviewing projects in a timely manner? Do researchers

find that the review process is substantively helpful? Is

the public being provided with the assurance that social

and ethical issues are being considered?

Summary

Recent developments in human stem cell research have

raised hopes that new therapies will become available

that will serve to relieve human suffering. These developments also have served to remind society of the deep

moral concerns that are related to research involving

human embryos and cadaveric fetal tissue. Serious ethical discussion will (and should) continue on these issues.

However, in light of public testimony, expert advice, and

published writings, we have found substantial agreement

among individuals with diverse perspectives that

although the human embryo and fetus deserve respect as

forms of human life, the scientific and clinical benefits of

stem cell research should not be foregone. We were persuaded that carrying out human stem cell research under

federal sponsorship is important, but only if it is conducted in an ethically responsible manner. And after

extensive deliberation, the Commission believes that

acceptable public policy can be forged, in part, on widely

shared views. Through this report, we not only offer recommendations regarding federal funding and oversight

of stem cell research, but also hope to further stimulate

the important public debate about the profound ethical

issues regarding this potentially beneficial research.

Introduction

Late in 1998, three separate reports brought to the

fore the debate over the scientific and clinical

prospects as well as the ethical implications of research

using human stem cells—those cells from which the

different types of cells in a developing organism grow and

that generate new cells throughout an organism’s life (Van

Blerkom 1994). The initial two reports were published

by two independent teams of scientists that had accomplished the isolation and culture of human embryonic

stem cells (hereafter referred to as ES cells) and embryonic

germ cells (hereafter referred to as EG cells). The first

report described the successful isolation of EG cells in the

laboratory of John Gearhart and his colleagues at The

Johns Hopkins University. This team derived stem cells

from primordial gonadal tissue obtained from cadaveric

fetal tissue (Shamblott et al. 1998). The second described

the work of James Thomson and his coworkers at the

University of Wisconsin, who derived ES cells from 

the blastocyst (~100 cells) of an early human embryo

donated by a couple who had received infertility treatments (Thomson et al. 1998). Finally, an article in the

November 12, 1998, edition of the New York Times

described work funded by Advanced Cell Technology of

Worcester, Massachusetts. Although this work has not

yet been verified fully or published in a scientific journal,

the company claims that its scientists have caused human

somatic cells to revert to the primordial state by fusing

them with cow eggs to create a hybrid embryo. From this

hybrid embryo, a small clump of cells resembling human

ES cells appears to have been isolated (Wade 1998).

Human Stem Cells: An Overview

Although many kinds of stem cells exist within the

human body, scientists recognize a hierarchy of types.

Some stem cells are more committed—or differentiated—

than others. At the earliest stage of embryonic development, the cells of the blastomere are identical to each

other and are relatively undifferentiated. Each one is

individually capable of generating a whole organism,

a quality referred to as totipotency. In the next stage,

ES cells, although they no longer are capable of producing a complete organism, remain undifferentiated and

retain the ability to develop into nearly any cell type

found in the human body, representing a type of biological plasticity referred to as pluripotency. (The terms

totipotency and pluripotency will be discussed again later

in this chapter.) At this point, the ES cells branch out

into many types; from each differentiated line, all the

specialized cells (e.g., heart, muscle, nerve, skin, or

blood) that constitute the tissues and organs of the body

will develop (Weiss et al. 1996).

The potential versatility of ES and EG cells derived

from the early stage embryo or from cadaveric fetal tissue

offers unusual scientific and therapeutic promise.

Because these cells have the ability to proliferate and

renew themselves over the lifetime of the organism,

scientists have long recognized the possibility of using

such cells to generate a certain number of specialized

cells or tissues, which could permit the generation of new

cells or tissue as a treatment for injury or for damage

done by diseases such as Alzheimer’s disease, Parkinson’s

disease, heart disease, and kidney failure. Furthermore,

scientists regard these cells as an important, perhaps

essential, medium for understanding the details of

1

1

Introduction

Chapter One
2

Chapter 1: Introduction

human development and thus for developing life-saving

drugs and other therapies. At the same time, the current

source of these cells (the early stage embryo or cadaveric

fetal tissue) makes them the subject of significant ethical

considerations. Thus, the scientific reports of the successful isolation of these versatile cells simultaneously

have raised the prospect of the development of new

treatments and perhaps cures for debilitating and even

fatal illnesses, while also renewing the debate regarding

the ethics of research involving human embryos and

cadaveric fetal material.

Ethical Issues

Within days of the publication of these reports and the

New York Times article, President Clinton wrote to the

National Bioethics Advisory Commission with two

requests: that the Commission consider the implications

of the purported cow-human fusion experiment and

report back to him and that it “undertake a thorough

review of the issues associated with human stem cell

research balancing all ethical and medical considerations.” On November 20, 1998, we responded to the

President’s first request by stating that “any attempt to

create a child through the fusion of a human cell and a

nonhuman egg would raise profound ethical concerns

and should not be permitted.” (See Appendix C, which

includes these letters of request and response.) Our

response was based upon the same principles we relied

on when preparing our report to the President entitled

Cloning Human Beings (1997). We noted, however, that

insufficient scientific evidence is available at this time to

determine whether the fusing of a human cell with the

egg of a nonhuman animal would result in a human

embryo. In addition, if the resulting hybrid embryo were

to be used as a source of ES cells, it is not clear that those

cells would be the same in all respects to those obtained

from a nonhybrid human embryo.

The reports of the successful isolation and culture of

ES and EG cells have added a new dimension to the

ongoing controversy regarding the ethics of research

involving human embryos and cadaveric fetal material.

This controversy arises from sharply differing moral

views regarding elective abortion or the use of embryos

for research, and it has fueled the national and international debate over the ethical, legal, and medical issues

that arise in this arena. This debate represents both a

challenge and an opportunity: a challenge because it concerns important and morally contested questions regarding the beginning of life, and an opportunity because it

provides another occasion for serious public discussion

about important ethical issues. We are hopeful that this

report will contribute to a dialogue that will foster

increased public understanding of the ethical issues

underlying research on ES and EG cells and an appreciation of the complexity of making responsible public policy in the face of moral disagreement and in light of a

realistic appraisal of the scientific and clinical promise of

that research.

We believe that most Americans agree that human

embryos should be respected as a form of human life, but

that disagreement exists both about the form that such

respect should take and about what level of protection is

owed at different stages of embryonic development.

Therefore, embryo research, the purpose of which is not

therapeutic to the embryo itself, is bound to raise serious

concerns for some about how to resolve the tensions

between the ethical imperative to cure diseases and the

moral obligation to protect human life. For those who

believe that the embryo has the moral status of a person

from the moment of conception, research (or any other

activity) that would destroy it is considered wrong and

should not take place. For others, arriving at an ethically

acceptable policy involves a complex balancing of a

number of important ethical concerns. Although this is a

controversial area, we should not lose sight of a broad

area of consensus on which public policy could—in

part—be constructed.

In order to respond effectively and responsibly to the

President’s request to consider issues related to human

stem cell research and to “balance all medical and ethical

considerations,” we determined that it also is necessary to

consider certain aspects of the broader issues regarding

research using embryonic and/or fetal material. One

reason for this approach is that the nature of some of the

ethical issues involved depends on the source of the stem

cells. For example, ES cells can be derived from early

embryos that are destroyed in the process of ES cell
3

National Bioethics Advisory Commission

derivation, an act that some people find ethically unacceptable. The use of cadaveric fetal tissue to derive EG

cell lines is somewhat less controversial because the fetus

is deceased prior to the initiation of the research and

because a well-developed system of public oversight for

such research is already in place. In addition, the recent

demonstration of nuclear transfer techniques (somatic

cell nuclear transfer [SCNT]) suggests that transfer of 

an adult nucleus into an oocyte might under certain

conditions create an embryo. However, the use of this

technique to combine an animal oocyte with a human

diploid nucleus raises additional issues regarding both

the nature of the embryo produced and the ethical issues

involved. In addition, each source of material bears a

unique set of scientific, ethical, and legal distinctions.

We believed that it was especially important to take a

broad view of the status of the human embryo and of

fetal tissue in relation to biomedical research, because it

is likely that science will uncover additional characteristics of the early ex utero human embryo or fetal tissues

that will raise additional important and unique therapeutic possibilities, separate from those that derive from 

ES or EG cells. If these developments occur, all of the

same ethical considerations that pertain to embryo

research and fetal tissue research in general would arise

once again.1 In fact, the 1994 National Institutes of

Health Human Embryo Research Panel designated 13 areas

in which embryo research could advance scientific

knowledge or could lead to important clinical benefits.

Among these areas is “the isolation of pluripotential

embryonic stem cell lines for eventual differentiation and

clinical use in transplantation and tissue repair.”2

Recent scientific developments require the updating

and review of the important work of U.S. bodies that

have met previously to address the role of the ethical

complexities of human embryo and fetal tissue research,

particularly as they relate to the role of federally funded

research. In addition, new policy statements from other

countries (such as Canada and the United Kingdom) 

suggest well-thought-out novel approaches that must be

considered carefully. In responding to the President’s

request, therefore, we elected to take a comprehensive

approach that built on the work of these reflective efforts,

both in this country and abroad.

In our 1997 report, Cloning Human Beings, we

addressed a specific aspect of cloning, namely where

genetic material would be transferred from the nucleus of

a somatic cell of an existing human being to an enucleated

human egg with the intention of creating a child. At the

time that we were preparing this report, the issues surrounding embryo research were not revisited, although

we began our discussions recognizing that any effort 

in humans to transfer a somatic cell nucleus into an

enucleated egg likely involves the creation of an embryo,

which has the potential to be transferred to a uterus and

developed to term. We recognized that ethical concerns

surrounding issues of embryo research recently had

received extensive analysis and noted that under current

law, the use of SCNT to create an embryo solely for

research purposes is prohibited in any project involving

federal funds. The President’s request—together with

new developments concerning human ES and EG cell

research using embryos remaining after infertility treatments or fetal tissue following elective abortion—

requires that we reconsider the appropriateness of using

these sources of cells for research purposes.

In this respect it is important to note that research on

human embryos, or the creation of human embryos for

research purposes, is not only legal in the United States

but proceeds without any public oversight as long as 

1) federal funds are not involved, 2) Food and Drug

Administration regulations do not apply, and 3) the laws

of the state in which the research is to be conducted do

not forbid such activity. Consequently, most of the

public controversy surrounding such activities in the

United States has focused on whether it is appropriate for

the federal government to sponsor such research when it

has significant scientific merit and substantive clinical

promise. This question is also the focus of this report.

Framework for This Report

As noted above, President Clinton directed the

Commission to conduct a thorough review of the issues

associated with human stem cell research balancing all

ethical and medical considerations. This approach—

balancing or weighing difficult issues—often is used in

public policy discussions and has much to recommend
4

Chapter 1: Introduction

it, particularly when such balancing involves a serious

consideration of different moral points of view, the state

of scientific and medical developments, and other factors. As discussed more fully in Chapter 4, some of the

issues associated with research on human stem cells—the

moral status of the human embryo, for example—are

especially sensitive and do not lend themselves easily to

balancing. We did not, for example, deem the views of

those who consider the fetus to have the moral status of

a human person from the moment of conception to be of

less (or more) moral weight than the views of those who

consider the fetus to lack this moral status. Similarly, we

did not come to our conclusions simply by balancing

potential medical benefits against the potential harms,

because the possibility of social benefits, by itself, is not

a sufficient reason for federal support of such controversial research, particularly given the interest in stem cell

research in the private sector. Nor did we approach this

issue based simply upon an interpretation of the existing

legal environment. Instead, we combined, as thoughtfully as we could, a number of different perspectives on

and approaches to this topic.

Through ongoing discussion and dialogue—

informed by scientists, philosophers, legal and religious

scholars, members of the public, and others—we developed our moral perspectives on the appropriateness of

federal sponsorship of stem cell research involving the

derivation and/or use of ES and EG cells, principally

focusing on the ethical and scientific issues. We considered the sources of human EG and ES cells and the 

relevant moral differences that should be evaluated in

determining the acceptability of federal funding for the

derivation and/or use of cells from each of these sources.

In this regard, we were assisted by a number of commissioned papers each of which addressed different aspects

of the problem.3 We also benefited from the input of a

group of religious scholars from diverse faith traditions

whose views within and across traditions reflected the

diversity found within the public as a whole. We then

considered some associated ethical issues including

voluntary informed consent, the just distribution of

potential benefits from stem cell research, and the commodification and sale of the body and its parts. Finally,

we considered how and to what extent a mechanism of

national oversight and review would provide the necessary assurance that research, conducted responsibly and

with accountability, could go forward while protecting

and honoring a number of deeply held values. These

shared values include

■ securing the safety and efficacy of clinical and/or 

scientific procedures, especially when fundamental

ethical and social issues are involved,

■ respecting human life at all stages of development,

and

■ ensuring the responsible pursuit of medical and 

scientific knowledge.

Although this report primarily addresses the ethical

issues associated with the use of federal funds for

research to derive and use ES and EG cells, we recognize

that considerable work in both of these areas will be conducted under private sponsorship. Thus, our recommendations also may have implications for those working in

the private sector.

Definitions Used in This Report

We recognize the need to define clearly the terms that are

central to an understanding of this report. Because certain terms, such as embryo and totipotent, are not always

used consistently, it is important to explain how the

Commission uses this terminology.

It is most important that the reader understand how

the term embryo is used. The Canadian Royal

Commission on New Reproductive Technologies elucidated the confusion surrounding the term well in its

1993 report entitled Proceed with Care: Final Report of the

Royal Commission on New Reproductive Technologies:

...In the language of biologists, before implantation

the fertilized egg is termed a ‘zygote’ rather than an

‘embryo.’ The term ‘embryo’ refers to the developing

entity after implantation in the uterus until about

eight weeks after fertilisation. At the beginning of the

ninth week after fertilisation, it is referred to as a

‘fetus,’ the term used until time of birth. The terms

embryo donation, embryo transfer, and embryo

research are therefore inaccurate, since these all occur

with zygotes, not embryos. Nevertheless, because the

terms are still commonly used in the public debate,
5

National Bioethics Advisory Commission

we continue to refer to embryo research, embryo

donation, and embryo transfer (607). 

For the sake of consistency and accuracy, when referring to the details of the developmental stages of an entity,

we use the following terminology: 1) the developing

organism is a zygote during the first week after fertilization, 2) the organism is an embryo during the second

through eighth weeks of development, and 3) the organism is a fetus from the ninth week of development until

the time of birth. However, in other contexts, we will

continue to use the broad terms embryo research, embryo

donation, and embryo transfer to refer to zygotes, because

this is how the public commonly uses them.

Because there are several sources of human stem cells,

we decided that each type of stem cell should be named

in a way that clarifies its original source. Therefore, as

discussed earlier, cells derived from the inner cell mass of

a blastocyst—those cells within the conceptus that form

the embryo proper—are called ES cells, and cells that 

are derived from primordial germ cells of embryos and

fetuses are called EG cells. In addition, cells derived

from teratocarcinomas—malignant embryonic tumors—

are called embryonal carcinoma cells, and stem cells found

in the adult organism are called adult stem (AS) cells.

Two other terms that require explanation—because

the scientific community disagrees about their meaning—

are totipotent and pluripotent. Some differentiate between

the two terms by defining totipotency as the ability to

develop into a complete organism and pluripotency as

the ability to develop into all of the various cell types of

an organism without the capability of developing into an

entire organism. Others define a totipotent cell as any cell

that has the potential to differentiate into all cells of a

developing organism, but that does not necessarily have

the ability to direct the complete development of an

entire organism. These scientists would then define a

pluripotent cell as any cell that has the ability to differentiate into multiple (more than two) cell types. Rather

than engage in this debate, for the sake of clarity, we

decided to avoid using this terminology in this report,

unless it refers directly to specific work or to the statements of others in which these words were included.

Instead, this report uses descriptions of the stage of

development and the differentiation potential of cells to

make clear to the reader which types of cells are being

discussed.

Organization of This Report

This report comes at a time when the Commission has

completed deliberations regarding the use of human biological materials in research (1999). In that report, we

recognized that in research involving such materials as

DNA, hair, and skin biopsies, a number of significant ethical issues must be addressed by Institutional Review

Boards, researchers, and others; these include issues of

privacy and confidentiality, potential discrimination,

and stigmatization. As important as these issues are—and

they must be handled satisfactorily in order for research

to proceed with appropriate protections for human subjects—research on human stem cells, whether they are

obtained from fetal tissue following elective abortions

or from tissue obtained from embryos remaining after

infertility treatments, requires additional and perhaps

even deeper ethical reflection.

The Commission’s primary goal for this report was

the development of a set of recommendations that would

provide guidance on the appropriateness of permitting

the federal government to fund human ES and EG cell

research and on what sorts of constraints, if any, should

be placed on such support. This report first presents a

summary of some of the key scientific issues involved in

stem cell research (Chapter 2). To place our analysis in

context and to understand the implications of any new

recommendations regarding the oversight and regulation

of research using fetal tissue and embryos, Chapter 3

describes the historical and current status of law and

regulation governing the research use of these materials.

Chapter 4 explores the various ethical issues surrounding

the moral status of the embryo and cadaveric fetal tissue

and ethical concerns governing the acceptable use of

these materials in research. Finally, Chapter 5 offers our

conclusions and recommendations regarding federal

sponsorship of research and appropriate oversight

activities in these ethically controversial areas.
6

Chapter 1: Introduction

Notes

1 For example, it has been generally recommended by most governmental and professional bodies that have previously examined

this issue that research on the ex utero pre-implantation embryo

should not be conducted beyond the 14th day following fertilization. At 14 days, the first stages of organized development begin,

leading over the next few days to the first appearance of differentiated tissues of the body. The Commission concurs with this time

limit on research involving the ex utero human embryo.

2 The 1994 National Institutes of Health Human Embryo Research

Panel was asked to consider various areas of research involving the

ex utero pre-implantation human embryo and to provide areas that

1) are acceptable for federal funding, 2) warrant additional review,

and 3) are unacceptable for federal support. The panel did not

consider research involving in utero human embryos, or fetuses,

because guidelines for such research already exist in the form of

regulations.

3 See Appendix H for a list of the papers that were prepared for

the Commission. These papers are available in Volume II of this

report.

References

Canadian Royal Commission on New Reproductive Technologies.

1993. Proceed with Care: Final Report of the Royal Commission on

New Reproductive Technologies. 2 vols. Ottawa: Minister of

Government Services. 

National Bioethics Advisory Commission (NBAC). 1997. Cloning

Human Beings. 2 vols. Rockville, MD: U.S. Government Printing

Office.

———. 1999. Research Involving Human Biological Materials: Ethical

Issues and Policy Guidance. 2 vols. Rockville, MD: U.S. Government

Printing Office.

National Institutes of Health (NIH). Human Embryo Research

Panel. 1994. Report of the Human Embryo Research Panel. 2 vols.

Bethesda, MD: NIH. 

Shamblott, M.J., J. Axelman, S. Wang, E.M. Bugg, J.W. Littlefield,

P.J. Donovan, P.D. Blumenthal, G.R. Huggins, and J.D. Gearhart.

1998. “Derivation of Pluripotent Stem Cells from Cultured Human

Primordial Germ Cells.” Proceedings of the National Academy of

Sciences USA 95:13726–13731. 

Thomson, J.A., J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, 

J.J. Swiergiel, V.S. Marshall, and J.M. Jones. 1998. “Embryonic

Stem Cell Lines Derived from Human Blastocysts.” Science

282:1145–1147.

Van Blerkom, J. 1994. “The History, Current Status, and Future

Direction of Research Involving Human Embryos.” In NIH Human

Embryo Research Panel, Report of the Human Embryo Research

Panel, Vol. II: Papers Commissioned for the Human Embryo Research

Panel, 1–25. Bethesda, MD: NIH.

Wade, N. 1998. “Researchers Claim Embryonic Cell Mix of Human

and Cow.” New York Times 12 November, A-1.

Weiss, S., B.A. Reynolds, A.L. Vescovi, C. Morshead, C.G. Craig,

and D. van der Kooy. 1996. “Is There a Neural Stem Cell in the

Mammalian Forebrain?” Trends in Neurosciences 19(9):387–393.
Introduction

The stem cell is a unique and essential cell type found

in animals. Many kinds of stem cells are found in

the human body, with some more differentiated—or

committed—to a particular function than others. In

other words, when stem cells divide, some of the progeny

mature into cells of a specific type (e.g., heart, muscle,

blood, or brain cells), while others remain stem cells,

ready to repair some of the everyday wear and tear

undergone by our bodies. These stem cells are capable of

continually reproducing themselves and serve to renew

tissue throughout an individual’s life. For example, they

continually regenerate the lining of the gut, revitalize

skin, and produce a whole range of blood cells. Although

the term stem cell commonly is used to refer to the cells

within the adult organism that renew tissue (e.g.,

hematopoietic stem cells, a type of cell found in the

blood), the most fundamental and extraordinary of the

stem cells are found in the early stage embryo (Van

Blerkom 1994). These embryonic stem (ES) cells, unlike

the more differentiated adult stem (AS) cells or other cell

types, retain the special ability to develop into nearly any

cell type. Embryonic germ (EG) cells, which originate from

the primordial reproductive cells of the developing fetus,

have properties similar to ES cells.

Because stem cells are able to proliferate and renew

themselves over the lifetime of the organism—while at

the same time retaining all of their multilineage

potential—scientists have long recognized that such cells

could be used to generate a large number of specialized

cells or tissue through amplification, a possibility that

could allow the generation of new cells that would treat

injury or disease.1 In fact, if it were possible to control

the differentiation of human ES cells in culture, the

resulting cells could be used to repair damage caused by

such conditions as heart failure, diabetes, and certain

neurodegenerative diseases.

In late 1998, three separate reports brought to the

fore not only these scientific and clinical prospects but

also the controversies inherent in human stem cell

research. The first two reports, published by two independent teams of scientists supported by private funds

from Geron Corporation, a biotechnology company

located in Menlo Park, California, describe the first successful isolation and culture in the laboratory of human

ES and EG cells. One team, led by John Gearhart of

The Johns Hopkins University School of Medicine in

Baltimore, Maryland, derived human EG cells from primordial gonadal tissue, which was obtained from fetal

tissue following elective abortion (Shamblott et al. 1998).

The second team, led by James Thomson of the

University of Wisconsin, derived human ES cells from

the blastocyst stage of early embryos donated by couples

who had undergone infertility treatment (Thomson et al.

1998). The ES and EG cells derived by each of these

means appear to be similar in structure, function, and

potential, although additional research is needed in order

to verify this claim (Varmus 1998). Finally, an article in

the November 12, 1998, edition of the New York Times

described work funded by Advanced Cell Technology of

Worcester, Massachusetts. Although this work has not yet

been verified fully or published in a scientific journal, the

company claims that its scientists have caused human

somatic cells to revert to the primordial state by fusing

them with cow eggs to create a hybrid embryo. From this

hybrid embryo, a small clump of cells resembling human

ES cells appears to have been isolated (Wade 1998). 

7

Human Stem Cell Research 

and the Potential for Clinical

Application

Chapter Two 2
8

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

The methodologies used by these investigators for

deriving human ES and EG cells are based on techniques

that have been used in mice since the early 1980s and,

more recently, from nonhuman primates and other animals. The isolation and culturing of these cells, however,

for the first time open certain avenues of important

research and future clinical possibilities. At the most

basic level, the isolation of these cells allows scientists to

focus on how human ES and EG cells differentiate into

specific types of cells, with the goal of identifying the

genetic and environmental signals that direct their specialization into specific cell types. Such studies using

mouse stem cells are ongoing, but comparable studies

with human cells will be required in order to determine

whether the signals are the same. This research might, for

example, lead to the discovery of new ways to treat a

variety of conditions, including degenerative diseases,

birth defects, and cancer and would build on investigations conducted over the last decade, in which laboratory animals have been used to determine whether ES

cells can be used to re-establish tissue in an adult organism (Corn et al. 1991; Diukman and Golbus 1992; Hall

and Watt 1989; Hollands 1991). Through processes scientists are only beginning to understand, these primitive

stem cells can be stimulated to specialize so that they

become precursors to different cell types, which then

may be used to replace tissues such as muscle, skin,

nerves, or liver. For example, in mid-1999, scientists

used mouse ES cells to successfully generate glial

(myelin-producing) cells that when transplanted into a

rat model of human myelin disease were able to efficiently myelinate axons in the rat’s brain and spinal cord

(Brustle et al. 1999).

Stem Cell Types

Scientists often distinguish between different kinds of

stem cells depending upon their origin and their potential to differentiate. Cells derived from malignant embryonic tumors, or teratocarcinomas, are called embryonal

carcinoma (EC) cells; cells derived from the inner cell mass

of a blastocyst-stage embryo are ES cells, and cells that are

derived from precursors of germ cells from a fetus are 

EG cells. In addition, stem cells can be found in the adult

organism, for example, in bone marrow; they may possibly also be found in skin and intestine. These AS cells

serve to replenish tissues in which cells often have 

limited life spans, such as the skin, intestine, and blood.

Although interesting new data suggest that stem cells

found in the adult organism are not restricted to producing cells from the tissue in which they reside (Bjornson et

al. 1999), it is unlikely that these cells are capable of differentiating into all cell types. In contrast, because

human ES and EG cells are believed to be capable of differentiating into all cell types, they are likely to be of clinical use in treating a variety of diseases, especially those

for which organ-specific stem cells are difficult to isolate

and/or use. 

EG Cells

Primordial germ cells are the embryonic precursors of

the sperm and ova of the adult animal (Donovan 1998).

The establishment of the germline in the embryo involves

the separation of primordial germ cells from the somatic

cells, the proliferation of primordial germ cells, the

migration of these cells to the gonads, and finally their

differentiation into gametes (Donovan 1994). Primordial

germ cells are the only cells in the body that can give rise

to successive generations, while the somatic cells that

form the body of the animal lack this capability as soon

as they start to differentiate (Matsui 1998). 

In culture, primordial germ cells can give rise to EG

cells that are capable of differentiating into cells of multiple lineages (Donovan 1998). (See Figure 2-1.) Primordial

germ cells normally give rise to gametes, but sometimes

if the developmental process goes awry, they become EC

cells, the stem cells of benign teratomas and malignant

teratocarcinomas, which are tumors containing derivatives of the three primary germ layers (Donovan 1998).

EG cells form embryoid bodies in culture, give rise to

teratomas when introduced into histocompatible animals, and form germline chimeras when introduced into

a host blastocyst (Donovan 1998). The derivation of EG

cells directly from primordial germ cells provides a

mechanism to study some aspects of primordial germ cell

development, such as imprinting and differentiation

(Donovan 1994). At the same time, it may be difficult to

obtain an adequate supply of appropriate fetal tissue to
9

National Bioethics Advisory Commission

provide the relevant cell lines needed for both research

and clinical uses.

ES Cells

In mammalian embryonic development, cell division

gives rise to differentiated daughter cells that eventually

comprise the mature animal. As cells become committed

to a particular lineage or cell type, a progressive decrease

in developmental potential presumably occurs. Early in

embryonic development (until about 16 cells), each cell

of the early cleavage-stage embryo has the developmental potential to contribute to any embryonic or extra

embryonic cell type (Winkel and Pedersen 1988).

However, by the blastocyst stage, the cells of the trophectoderm are irreversibly committed to forming the

placenta and other trophectoderm lineages (Winkel and

Pedersen 1988). By six to seven days postfertilization, the

inner cell mass has divided to form two layers, which

then give rise to the embryo proper and to extra

embryonic tissues (Gardner 1982). (See Exhibit 2-A

and Figure 2-2 for a description of early human

embryonic development.)

Although the cells of the inner cell mass are precursors to all adult tissues, they can proliferate and replace

themselves in the intact embryo only for a limited time

before they become committed to specific lineages

(Thomson and Marshall 1998). ES cells are derived from

cells of the inner cell mass. Once they are placed in the

appropriate culture conditions, these cells seem to be

capable of extensive, undifferentiated proliferation in

vitro and maintain the potential to contribute to all adult

cell types (Evans and Kaufman 1981; Martin 1981). (See

Figure 2-3.)

Even though these embryonic cells are stem cells,

they differ substantially from the stem cells found within

the fully developed, or adult, organism (see below). Most

important, ES cells are highly proliferative, both in the

embryo as well as in culture, while some stem cells of the

adult can be nearly quiescent and may be more difficult

to maintain and expand in culture (Van Blerkom 1994).

Therefore, it appears that if stem cells were someday to

be used for the treatment of disease, it might be advantageous to use ES cells to treat certain disorders.

Sources of Human ES Cells

We have distinguished between three sources of 

ES cells, which are derived from early embryos in culture: 1) embryos created by in vitro fertilization (IVF) for

infertility treatments that were not implanted because

they were no longer needed, 2) embryos created by IVF

Fertilization

Blastocyst

(6–7 days) (5–9 weeks)

Primordial

Germ Cells Cultured ES Cells

Specific Cell and 

Tissue Types

Cleavage

Elective

Abortion

Figure 2-1. Isolation and Culture of Human ES Cells from Embryonic/Fetal Tissue

EMBRYO/

FETUS
10

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

expressly for research purposes, and 3) embryos resulting

from somatic cell nuclear transfer (SCNT) or other

cloning techniques. SCNT technology has, in fact, opened

the door to a possible alternative approach to creating ES

cells. (See Figure 2-4.) If the nucleus is removed from an

immature egg (oocyte) and a mature diploid nucleus is

inserted, the resulting cell will divide and develop with

many characteristics of an embryo. In animal experiments

in which a SCNT-derived embryo is transferred to a

surrogate mother, a successful pregnancy may be established. (This was the technique used to generate the nowfamous cloned sheep Dolly.) If, instead of being transferred

to a surrogate, the SCNT-derived embryo is kept in culture,

is allowed to divide, and is then dissociated, ES cells can

Exhibit 2-A: Early Development of the Human Embryo 

In humans, fertilization (the union of an oocyte [egg] and sperm) occurs in the fallopian tubes and results in the 

formation of the zygote. In the three to four days it takes for the zygote to travel down the fallopian tube to the uterus,

several cell divisions (cleavages) occur.

The first division occurs approximately 36 hours after fertilization, when the zygote begins to cleave into two cells

called blastomeres. At about 60 hours following fertilization, the two blastomeres divide again to form four blastomeres. At three days postfertilization, the four blastomeres divide to form eight cells. Each blastomere becomes

smaller with each subsequent division. In this early stage of development, all of the blastomeres are of equal size.

These cells are unspecialized and have the capacity to differentiate into any of the cell types of the embryo as well

as into the essential membranes and tissue that will support the development of the embryo.Therefore, one or more

of the blastomeres can be removed without affecting the ability of the other blastomeres to develop into a fetus. In

fact, if an embryo separates in half during this early stage of development, identical twins—two genetically identical

individuals—will develop.

When the cell division reaches approximately 16 cells, the zygote is called a morula. The morula leaves the 

fallopian tube and enters the uterine cavity three to four days following fertilization. After reaching the uterus,

the developing zygote usually remains in the uterine cavity an additional four to five days before it implants in the

endometrium (uterine wall), which means that implantation ordinarily occurs on the seventh or eighth day following

fertilization.

Cell division continues, creating a cavity known as a blastocele in the center of the morula. With the appearance

of the cavity in the center, the entire structure is now called a blastocyst. This first specialization event occurs just

before the zygote attaches to the uterus, approximately six to seven days after fertilization, when approximately 100

cells have developed. This specialization involves the formation of an outer layer of trophoblast cells, which will give

rise to part of the placenta, surrounding a group of about 20 to 30 inner cells (the inner cell mass) that remain 

undifferentiated. At this stage, these cells no longer can give rise to all of the cells necessary to form an entire

organism and therefore are incapable of developing into an entire human being. In general, as cells further

differentiate, they lose the capacity to enter developmental pathways that were previously open to them.

As the blastocyst attaches to the uterus, the outer layer of cells secretes an enzyme, which erodes the epithelial

uterine lining and creates an implantation site for the blastocyst. Once implantation has taken place, the zygote

becomes an embryo. The trophoblast and underlying cells proliferate rapidly to form the placenta and the various

membranes that surround and nourish the developing embryonic cells.

In the week following implantation, the inner cells of the blastocyst divide rapidly to form the embryonic disc,

which will give rise to the three germ layers—the ectoderm, the mesoderm, and the endoderm. These three layers

will eventually develop into the embryo. By 14 days, the embryonic disc is approximately 0.5 mm in diameter and

consists of approximately 2,000 cells. It is at this time that the first stage of organized development, known as 

gastrulation, is initiated, leading over the next few days to the first appearance of differentiated tissues of the 

body, including primitive neural cells. Gastrulation is the process by which the bilaminar (two-layered) embryonic disc

is converted into a trilaminar (three-layered) embryonic disc, and its onset at day 14 in vivo is marked by the appearance of the primitive streak, a region in which cells move from one layer to another in an organized way.

During the third week, the embryo grows to 2.3 mm long, and the precursors of most of the major organ systems

begin to form. At the beginning of the third month, the embryo becomes a fetus. During the third to ninth months,

the organ systems and tissues of the fetus continue to develop, until birth.
11

National Bioethics Advisory Commission

be derived. The potential advantage of using SCNT technology to create ES cells is that a somatic cell from an

individual can be used to create ES cells that are completely compatible with that individual’s tissue type. If

cells or tissues are generated from these ES cells for transplant into a person, this tissue type compatibility may

avoid many of the problems associated with tissue graft

rejection that are currently encountered in the treatment

of a variety of diseases.

The use of SCNT into an oocyte has been criticized as

an asexual or “unnatural” way of creating a human

embryo. However, it is important to distinguish the technique of SCNT from the type of cell that is created; in

other words, SCNT techniques also might be used with

recipient cells other than oocytes. For example, ES cells with

matched tissue types for transplant might be generated

by SCNT into an enucleated ES cell.2 This possibility

has not yet been explored, but it may be less morally

Sperm

Egg

In Utero

Fertilization

Day 6–7

Blastocyst

Day 1– 6

Cell Division

(Cleavage)

Zygote

(week 1)

Embryo

(weeks 2–8)

Fetus

(months 3–9)

Figure 2-2. Stages of Development of the Human Embryo and Fetus

Embryo Fetus

In Vitro

Fertilization

Blastocyst

(6–7 days)

Cells from

Inner Cell Mass Cultured ES Cells

Specific Cell and Tissue Types

Cleavage

Inner Cell Mass

Figure 2-3. Isolation and Culture of Human ES Cells from Blastocysts
12

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

problematic to many citizens, because the cell created

would not be an embryo with the potential to continue

developing. 

Stem Cells Found in the Postnatal 

and Adult Organism

In the adult mammal, cell division occurs in order to

maintain a constant number of terminally differentiated

cells in tissues in which cells have been lost due to injury,

disease, or natural cell death. Cells with a high turnover

rate are replaced through a highly regulated process of

proliferation, differentiation, and apoptosis (programmed

cell death) from relatively undifferentiated stem cells, or

precursor cells (Thomson and Marshall 1998). The best

known example of an AS cell is the hematopoietic stem

cell, which is found in bone marrow and which is

responsible for the production of all types of blood cells

(Iscove 1990). Other examples of stem cells include the

skin epithelium and the epithelium of the small intestine

(Hall and Watt 1989). In the human small intestine, for

example, approximately 100 billion cells are shed and

must be replaced daily (Potten and Loeffler 1990). These

tissues contain subpopulations of dividing stem cells that

generate replacements for the relatively short-lived, terminally differentiated cells. Much of the debate in the

stem cell field revolves around determining the breadth

of the potential of these cells: Can they generate only the

cells of that organ or are they capable of differentiating

into several types of cells when given the proper stimuli?

The successful cloning of Dolly demonstrated that

even somatic cells are capable of forming every cell of an

organism after nuclear transfer into an oocyte (Wilmut et

al. 1997). Preliminary studies of stem cells obtained from

various systems of the adult organism suggest that in

some cases the reactivation of dormant genetic programs

may not require nuclear transfer or experimental modification of the genome. Although research in this area is

preliminary, this particular class of stem cells (i.e., AS

cells) might be able to differentiate along several cell

lineages in response to an appropriate pattern of

stimulation.

Neural Stem Cells

For a number of years, scientists have recognized

that transplantation of fresh fetal neural tissue into the

diseased adult brain may be a promising therapy for

neurodegenerative disorders. This type of transplantation

recently has been shown to be effective in younger

patients with Parkinson’s disease (Freed et al. 1999). This

technique has several disadvantages, however, such as

the need to time the surgery according to the availability

of large amounts of fresh fetal tissue, the need to quickly

Enucleated

Egg

Somatic

Cell

Blastocyst

(6–7 days)

Cells from

Inner Cell Mass Cultured ES Cells

Specific Cell and 

Tissue Types

Somatic Cleavage

Cell Nuclear

Transfer

Figure 2-4. Isolation and Culture of Human ES Cells from SCNT
13

National Bioethics Advisory Commission

screen for infectious diseases, and the limited amount of

donor fetal tissue available (Bjorklund 1993; Cattaneo

and McKay 1991). By developing techniques to culture

and expand primary fetal neural cells before transplantation, some of the problems of using fresh tissue may be

eliminated. In addition, it might be possible to direct cultured cells to develop along certain lineages or to express

specific genes before they are transplanted, so that, for

example, dopamine-producing cells could be selectively

grown to treat Parkinson’s disease (Cattaneo and McKay

1991; Snyder 1994).

Indeed, it has already been demonstrated that neural

stem cells are capable of gene (Snyder, Taylor, and Wolfe

1995) and cellular (Rosario et al. 1997; Snyder et al.

1997; Yandava, Billinghurst, and Snyder 1999) replacement in models of neural disease. In many of these experiments, one stable clone of mouse neural stem cells could

be used from individual to individual, strain to strain,

and disease to disease, regardless of recipient age within

the species, without immunorejection or the need for

immunosuppression. This suggests that unique immune

qualities may exist within stem cells that might allow

them to be universal donors. Moreover, the possibility

exists that many of the instructive cues for differentiation

actually might originate from interaction with damaged

central nervous system tissue itself.

The embryonic nervous system arises from the

ectoderm. The first cell type to differentiate from the

uncommitted precursor cells is the neuron, followed by

the oligodendrocyte, and then the astrocyte (Frederiksen

and McKay 1988). Recently, Angelo Vescovi, a neurobiologist at the National Neurological Institute Carlo Besta in

Milan, Italy, and his colleagues reported that neural stem

cells, which give rise to the three main types of brain

cells, also can become blood cells when transplanted

into mice in which the blood-forming tissue—the bone

marrow—has been mostly destroyed (Bjornson et al.

1999). Although the study did not explain what caused

the neural cells to turn into blood cells, the investigators

speculate that the neural cells might be responding to the

same signals that normally stimulate the few remaining

blood stem cells to reproduce and mature after irradiation destroys most of the bone marrow (Strauss 1999).

Although this research is preliminary and has not yet

been conducted using human cells, it raises the possibility of using neural stem cell transplants to treat human

blood cell disorders such as aplastic anemia and severe

combined immunodeficiency. This is an appealing

prospect, because bone marrow stem cells do not replenish themselves well in laboratory cultures. The problem

of access to such cells in humans remains, as they must

be obtained from the brain—an invasive and risky procedure. This research also opens up the possibility that

other apparently restricted AS cells may retain the ability

to differentiate into several different types of cells if

exposed to a conducive external environment. It is clear

that further research is required in this area.

Mesenchymal Stem Cells

Human mesenchymal stem cells, which are present in

adult bone marrow, can replicate as undifferentiated cells

and have the potential to differentiate into lineages of

mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma (Pittenger et al. 1999).

In a recent experiment, cells that have the characteristics

of human mesenchymal stem cells were isolated from

marrow aspirates of volunteer donors. Individual stem

cells were identified that, when expanded to colonies,

retained their multilineage potential. These results

demonstrate that isolated expanded human mesenchymal stem cells in culture will differentiate, in a controlled

manner, to multiple but limited lineages. One might

speculate that these particular AS cells could be induced

to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages, which then might be used to

treat various bone diseases.

The specific environmental cues needed to initiate the

proliferation and differentiation of these cells are not

understood (Pittenger et al. 1999). The ability to isolate,

expand, and direct the differentiation of such cells in

culture to particular lineages, however, offers the opportunity to study events associated with cell commitment

and differentiation. The human mesenchymal stem cells

isolated by Pittenger and colleagues appear to have the

ability to proliferate extensively and to maintain the ability to differentiate into certain cell types in culture. Their

cultivation and selective differentiation should provide

further information about this important progenitor of
14

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

multiple tissue types and the potential of new therapeutic approaches for the restoration of damaged or diseased

tissue (Pittenger et al. 1999). 

Animal Models

ES cells were first derived from mouse embryos, and the

mouse has become the principal model for the study of

these cells (Evans and Kaufman 1981; Martin 1981). If

mouse ES cells are injected into the developing blastocyst, they have the ability to contribute to all three germ

layers of the mouse, including the germline, to form a

chimeric animal. This is one of the unique properties of

the mouse ES cell. More recently, cells with some properties of ES cells have been derived from cows, pigs, rats,

sheep, hamsters, rabbits, and primates (Pedersen 1994).

(See Table 2-1.) However, only in cows, pigs, and rats

did these ES cells contribute to a chimeric animal, and in

none of these cases was there contribution to the

germline by ES cells, one of the most stringent criteria for

defining ES cells.

Mouse ES Cells

ES cells were first isolated from mouse blastocysts in

1981 (Evans and Kaufman 1981; Martin 1981). These

blastocysts were placed in culture and allowed to attach

to the culture dish so that trophoblast cells spread out,

while the undifferentiated inner cells (the inner cell mass)

continued to grow as a tight but disorganized cluster.

Before the inner cell mass developed into the equivalent

of the embryonic disc, it was drawn up into a fine

pipette, dissociated into single cells, and dispersed into

another dish with a rich culture medium. Under these

circumstances, the dissociated cells continued to grow

rapidly for an extended period.

Mouse ES cells cannot become organized into an

embryo by themselves or implant into the uterus if

placed there. However, if the cells are injected back into

a new blastocyst, they can intermingle with the host

inner cell mass to make a chimera and participate in normal development, eventually contributing to all of the

tissues of the adult mouse, including nerve, blood, skin,

bone, and germ cells (Robertson and Bradley 1986). This

Table 2-1. Stem Cells Isolated from

Mammals

Species References

Mouse Evans and Kaufman 1981

Martin 1981

Rat Iannaccone et al. 1994

Hamster Doetschman, Williams, and

Maeda 1988

Mink Sukoyan et al. 1992

Sukoyan et al. 1993

Rabbit Moreadith and Graves 1992

Giles et al. 1993

Graves and Moreadith 1993

Sheep Handyside et al. 1987

Piedrahita, Anderson, and

Bondurant 1990

Notarianni et al. 1991

Pig Piedrahita et al. 1988

Evans et al. 1990

Notarianni et al. 1990 

Piedrahita et al. 1990

Hochereau-de Reiviers and

Perreau 1993

Talbot et al. 1993

Wheeler 1994

Shim et al. 1997

Cow Evans et al. 1990

Saito, Strelchenko, and 

Niemann 1992

Strelchenko and Stice 1994

Cibelli et al. 1998

Common Marmoset Thomson et al. 1996

Rhesus Monkey Thomson et al. 1995

Human Bongso et al. 1994

Shamblott et al. 1998 

Thomson et al. 1998
15

National Bioethics Advisory Commission

indicates that mouse ES cells have not lost the capacity to

give rise to specialized tissues, but they will not do so

unless placed in a conducive environment.

The ability of mouse ES cells to enter the germline in

chimeras allows the introduction of specific genetic

changes into the mouse genome and offers a direct

approach to understanding gene function in the intact

animal (Rossant, Bernelot-Moens, and Nagy 1993).

Using the technique of homologous recombination in

which a gene is either modified or disabled (“knocked

out”), mouse ES cells that contain specific gene alterations may be derived. These genetically altered cells can

then be used to form chimeras with normal embryos,

subsequently generating a mouse lacking one specific

gene or containing an extra or altered gene.

Mouse ES cells also have been extremely useful as

models of the early differentiation events that occur during the development of mammalian embryos (Pedersen

1994), as shown in the following examples:

■ When mouse ES cells were allowed to differentiate in

culture, beating heart cells formed spontaneously,

providing a model for cardiac-specific gene expression and the development of cardiac muscle and

blood vessels (Chen and Kosco 1993; Doetschman et

al. 1993; Miller-Hance et al. 1993; Muthuchamy et al.

1993; Robbins et al. 1990; Wobus, Wallukat, and

Heschler 1991).

■ Blood formation will occur spontaneously in ES cellderived embryoid bodies and can be augmented by

modifying the culture conditions (Snodgrass,

Schmitt, and Bruyns 1992). Therefore, hematopoietic

stem cells have been studied extensively in an effort

to determine the conditions for differentiation, survival, and proliferation of blood cells.

■ Several studies have highlighted the importance of

growth and differentiation factors in the regulation of

mammalian development. For example, the maintenance of mouse ES cells in an undifferentiated state

was found to require the presence of leukemia

inhibitory factor, a differentiation-inhibiting factor

(Fry 1992). Other studies have found several growth

and differentiation factors to be important in ES cell

development and differentiation, including activins,

colony-stimulating factor, erythropoietin, basic

fibroblast growth factor, insulin-like growth factor 2,

interleukins, parathryoid hormone-related peptide,

platelet-derived growth factor, steel factor, and transforming growth factor ß (Pedersen 1994).

■ In midgestation embryos and the adult mouse, only

one parental allele of imprinted genes is expressed.

However, studies have suggested that there is

limited relaxation of imprinting in ES cells so that

both maternal and paternal alleles are expressed

(Pedersen 1994).

By understanding the mechanisms responsible for

growth and differentiation in embryonic development, it

may then be possible to attempt to regulate the differentiation of ES cells along specific pathways. The knowledge gained from these types of studies could someday

lead to the effective treatment of certain important

human diseases.

Historically, because of its well-defined genetics, short

gestational time, ease of cultivation, and large litters, the

mouse has been one of the primary models for the study

of mammalian embryonic development. However, there

are several differences between early mouse development

and early human development, including 

■ the timing of embryonic genome expression (Braude,

Bolton, and Moore 1988),

■ the formation, structure, and function of the fetal

membranes and placenta (Benirschke and Kaufmann

1990; Luckett 1975, 1978), and

■ the formation of an egg cylinder (mouse) as opposed

to an embryonic disc (human) (Kaufmann 1992;

O’Rahilly 1987).

Thus, other animal models as well as new models that

would allow the direct study of human embryonic development are crucial in order to comprehend early human

development and to understand the growth requirements

of human stem cells of specific lineages.

Bovine ES Cells

The first bovine ES-like cells were reported by Saito,

Strelchenko, and Niemann in 1992. More recently, transgenic bovine ES-like cells were derived by using nuclear

transfer of fetal fibroblasts to enucleated bovine oocytes

(Cibelli et al. 1998). This technique involved introducing

a marker gene into bovine fibroblasts from a 55-day-old

fetus and then fusing the transgenic fibroblasts to

enucleated oocytes to produce blastocyst-stage nuclear
16

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

transplant embryos (Cibelli et al. 1998). ES-like cells

then were derived from these embryos and were used 

to create chimeric embryos. When reintroduced into 

pre-implantation embryos, these transgenic ES-like cells

differentiated into derivatives from the three EG layers—ectoderm, mesoderm, and endoderm (Cibelli et al.

1998). Bovine ES cells would be useful in agricultural

production of transgenic cows and also may have the

potential for generating tissues and organs for use in

cross-species transplantation (xenotransplantation) in

order to treat human diseases.

Primate ES Cells

Primate ES-like cells have been derived from both the

rhesus monkey (Thomson et al. 1995) and the common

marmoset (Thomson et al. 1996). When allowed to grow,

both marmoset and rhesus ES cells spontaneously differentiate into more complex structures, including cardiac

muscle, neurons, endoderm, trophoblast, and numerous

unidentified cell types (Thomson and Marshall 1998).

Essential characteristics of these primate ES-like cells

include 1) derivation from the pre-implantation or periimplantation embryo, 2) prolonged undifferentiated proliferation, and 3) stable developmental potential to form

derivatives of all three EG layers even after prolonged

maintenance in culture (Thomson and Marshall 1998).

In addition, although mouse ES cells rarely contribute to

trophoblast in chimeras (Beddington and Robertson

1989), primate ES cells differentiate into all three germ

layers and trophoblast-like cells (Thomson and Marshall

1998). Furthermore, some primate ES cell lines have

maintained a normal karyotype through undifferentiated

culture for at least two years, sustained a stable developmental potential throughout this culture period, and

maintained the potential to form trophoblast in vitro

(Thomson et al. 1995, 1996).

Although there is some variation between species,

nonhuman primate ES cell lines appear to provide a

useful in vitro model for understanding the differentiation

of human tissues (Thomson and Marshall 1998), and

primate ES cells provide a powerful model for understanding human development and disease. Furthermore,

because of the similarities between human and primate

ES cells, primate ES cells provide a model for developing

strategies to prevent immune rejection of transplanted

cells and for demonstrating the safety and efficacy of ES

cell-based therapies (Thomson et al. 1995).

Human Models

Human ES Cell Lines Derived from Blastocysts

The first successful isolation of cells from the human

inner cell mass of blastocysts and their culture in vitro for

at least two series of cell divisions was reported by

Bongso and colleagues in 1994. Starting with 21 spare

embryos donated by nine patients in an IVF program,3

this group isolated cells with typical stem cell characteristics from 17 five-day-old blastocysts (approximately

100 cells) (Bongso et al. 1994). These cells were like ES

cells. They were small and round with high nuclear to

cytoplasmic ratios, they stained positively for alkaline

phosphatase (a biochemical marker for stem cells), and

they maintained a normal diploid karyotype. However,

after the second subculture, the cells differentiated into

fibroblasts or died (Bongso et al. 1994).

In later work, Thomson and his colleagues were able

to isolate human ES-like cell lines and grow them continuously in culture for at least five to six months.

Although these cells have not passed the most stringent

test—as have mouse ES cells—to determine whether

they can contribute to the germline, we will continue to

use the term ES cell throughout this report because both

scientists and nonscientists alike have widely applied this

term to refer to these cells. This renewable tissue culture

source of human cells—capable of differentiating into a

wide variety of cell types—is believed to have broad

applications in basic research and transplantation therapies

(Gearhart 1998).

In Thomson’s work, human ES cells were isolated

from embryos that were originally produced by IVF 

for clinical reproductive purposes. (See Exhibit 2-B.)

Individuals donated the embryos, following an informed

consent process. The consent forms and the entire

research protocol were reviewed and approved by an

appropriately constituted Institutional Review Board

(IRB) (Thomson et al. 1998). Thirty-six embryos were

cultured for approximately five days. The inner cell mass

was isolated from 14 of the 20 blastocysts that developed,
17

National Bioethics Advisory Commission

and five ES cell lines, originating from five separate

embryos, were derived (Thomson et al. 1998). The technique used to derive these human ES cells is essentially

the same as that used to isolate nonhuman primate ES

cell lines (Thomson et al. 1995).

The resulting human ES cell lines had normal karyotypes (two male and three female) and were grown in

culture continuously for at least five to six months

(Thomson et al. 1998). In addition, the cell lines

expressed cell surface markers that also are found on

nonhuman primate ES cells (Thomson et al. 1998). Most

important, the cell lines maintained the potential to form

derivatives of all three EG layers—endoderm, mesoderm,

and ectoderm (Thomson et al. 1998).

Many believe that research using human ES cells

might offer insights into developmental events that cannot be studied directly in the intact human embryo but

that have important consequences in clinical areas such

as birth defects, infertility, and miscarriage. Some speculate that the origins of many human diseases (e.g., juvenileonset diabetes) are due to events that occur early in

embryonic development. Such cells also will be particularly valuable for the study of the development and function of tissues that differ between mice and humans.

These cells allow for studies that focus on the differentiation of cells into specific tissues and the factors that

bring about differentiation, so that cells can be manipulated to generate specific cell types for therapeutic transplantation. Moreover, it may be possible to identify gene

targets for new drugs, to manipulate genes that could be

used for tissue regeneration therapies, and to understand

the teratogenic or toxic effects of certain compounds

(Thomson et al. 1998). 

Human EG Cells from Fetal Primordial 

Germ Cells

Primordial germ cells also can give rise to cells with

characteristics of ES cells, and, as discussed previously,

Exhibit 2-B: In Vitro Fertilization (IVF)

The procedure of IVF today is widely available in many countries throughout the world, including the United

States. Originally developed for the treatment of infertility due to blocked fallopian tubes, IVF has been extended

to assist patients with premature depletion of oocytes, recurrent failure of embryos to implant, and low production

of functional sperm. More recently, the technique has been used in conjunction with pre-implantation genetic

diagnosis to enable fertile couples at risk for transmitting severe or fatal inherited diseases to have healthy 

children.

Although details of the IVF procedures vary from center to center, the basic approach is to treat oocyte donors

over several days with a regimen of hormones designed to stimulate the final maturation of several follicles 

within the ovary. This is known as hyperstimulation, a procedure that carries the risk of an adverse reaction of less

than 1 percent. Following completion of the hormone treatment, mature follicles are detected by sonography and

an average of ten are collected by transvaginal aspiration while the patient is sedated. The oocytes are then fertilized by sperm collected from a male donor and cultured in sterile fluid for about two days. When the zygote has

reached the four- to eight-cell stage, between three and six zygotes are transferred to the uterus, and the untransferred embryos, if they are developing normally, are usually frozen. Nonviable embryos are discarded. (See also

Figure 2-5.) More recently, IVF specialists have begun culturing embryos to the blastocyst stage before transfer

to the uterus.

The efficiency of the IVF procedure is relatively low, with approximately 20 percent of fertilized eggs resulting

in successful pregnancies, depending on factors such as age of the recipient and the reason for infertility. In 

comparison, approximately 30 percent of normally conceived human embryos result in successful pregnancies.

Embryos that are not transferred can be cryopreserved and stored indefinitely.

Sources:

National Institutes of Health (NIH). Human Embryo Research Panel. 1994. Report of the Human Embryo Research Panel. 2 vols. 

Bethesda, MD: NIH.

New York State Task Force on Life and the Law. 1998. Assisted Reproductive Technologies: Analysis and Recommendations for Public Policy.

New York: New York State Task Force on Life and the Law.
18

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

Figure 2-5. 1996 Assisted Reproductive Technology (ART) Success Ratesa

9,005 (62%) of live

births resulted in 

single births

5,519 (38%) of live

births resulted in 

multiple births

993 (18%) of 

multiple births were

triplets or greater

4,526 (82%) of 

multiple births 

were twins

aSource: Centers for Disease Control and Prevention (CDC), American Society for Reproductive Medicine, Society for Assisted

Reproductive Technology, and RESOLVE. 1998. 1996 Assisted Reproductive Technology Success Rates, National Summary and

Fertility Clinic Reports. Atlanta, GA: CDC. 

bData are from 300 U.S. fertility clinics that provided and verified information about the outcomes of all ART cycles started in

their clinics in 1996.

cFresh, nondonor cycles were canceled, most commonly because too few (egg) follicles developed. Illness unrelated to the 

ART procedure also may lead to cancelation. In general, cycles are canceled when chances of success are poor or risks are 

unacceptably high. 

dAdverse outcomes included spontaneous abortion (83%), induced abortion (10%), stillbirth (4%), and ectopic pregnancy (3%).

eA total of 20,659 babies were born as a result of the 64,036 ART cycles carried out in 1996.

64,036 

ART cyclesb

7,044 (11%) 

of ART cycles 

were canceledc

2,766 (16%) of 

pregnancies resulted

in adverse outcomesd

14,524 (84%) of 

pregnancies resulted

in live birthse

17,290 (27%) of ART

cycles resulted in

pregnancies
19

National Bioethics Advisory Commission

have been designated as EG cells in order to distinguish

their tissue of origin (Gearhart 1998). A 1998 report from

John D. Gearhart and his colleagues describes the establishment of human EG cell lines from human primordial

germ cells (Shamblott et al. 1998). Using an IRBapproved protocol, the human EG cells were isolated

from the developing gonads of five- to nine-week-old

embryos and fetuses that were obtained following elective abortion (Shamblott et al. 1998). These human EG

cell lines have morphological, immunohistochemical,

and karyotypic features consistent with those of previously described ES cells and have a demonstrated ability

to differentiate in vitro into derivatives of the three germ

layers (Shamblott et al. 1998).

Fusion of Human Somatic Cells with Cow Eggs

to Create Hybrid Embryonic Cells

Advanced Cell Technology of Worcester, Massachusetts,

announced in November 1998 that its scientists had

made human somatic cells revert to the primordial state

by fusing them with cow eggs to create a hybrid embryo

(Wade 1998). This work with human cells was performed in 1996 by Jose Cibelli. Using 52 of his own

cells—some of them white blood cells and others scraped

from the inside of his cheek—Cibelli used a pulse of electricity to fuse each cell with a cow egg from which the

nucleus containing the DNA had been removed.4 Out of

these 52 attempts, only one embryo, derived from a

cheek epithelial cell, developed into a blastocyst.

Approximately 12 days after the fusion of cheek cell and

cow egg, sufficient cells existed to allow harvesting of the

inner cell mass to produce cells resembling human ES

cells. The researchers observed that the hybrid cell quickly

became more human-like as the human nucleus took

control and displaced bovine proteins with human proteins. However, it is difficult to judge the validity of this

work and the nature of the “embryo-like” material produced because the work is extremely preliminary and has

not been submitted for peer review or for publication in

a scientific journal.

The stated purpose of these experiments was to create an embryo solely for the purpose of establishing an

ES cell line that might be used to treat any disease caused

by the loss or malfunction of cells, such as Parkinson’s

disease, diabetes, and heart disease. The researchers

emphasized that they had no intention of transferring the

resulting hybrid embryos to a uterus, as they considered

this to be both unethical and unsafe (Wade 1998).

Growth and Derivation of ES Cells

Human ES cells are different from many adult cells

because they have the ability to divide extensively in culture. Although this property has been interpreted by

nonscientists as an indication that investigators simply

can use existing human ES and EG cell lines (which can

be extensively reproduced for a limited time) to study

their properties, this is not the case and is a reflection of

a misunderstanding of the science that is involved.

Evidence from mouse ES cell research suggests that it is

essential to derive new ES cell lines repeatedly in order to

further our understanding of how to differentiate these

cells and grow them extensively in culture.

There are several reasons why it is necessary to

repeatedly derive new ES cell lines. First, the properties

of ES cells differ depending on the methods used to

derive them.5 Cells derived under some conditions may

be limited in their potential to differentiate into a particular tissue type. Second, ES cells are not stable cell types

that can simply be mass produced and supplied to an

unlimited number of researchers. As these cells grow in

culture they accumulate irreversible changes, and the

conditions used to grow them can influence the speed at

which these changes accumulate. Typically, researchers

look only at the ability of ES cells to contribute to some

tissues. In one study, however, the ability of ES cells to

generate all tissue in a mouse was tested (Nagy et al.

1993). This research has shown dramatically that existing

cell lines commonly in use by many researchers have lost

the ability to generate all mouse tissues and thus to completely generate live mice. When new ES cells were

derived and grown for only a short time in culture, they

did allow all tissues to be generated. However, after about

14 doublings in culture, even these cells lost their ability

to contribute to all tissues. The researchers conclude...

“[P]rolonged passage in culture reduces the potential of

the ES cell population as a whole. The proportion of

cells that retain full potential diminishes with extended
20

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

passage” (Nagy et al. 1993). Exactly what changes occur

during culture are not yet clear. The chromosome complement remains normal, indicating that this criterion,

although frequently used to characterize ES cells, is not a

very stringent assay. It could be an accumulation of mutations, changes in gene expression, or epigenetic changes

(Nagy et al. 1993). Thus, if one scientist were to obtain

cells from a colleague’s laboratory, the properties of the

cells would depend greatly on the history of how those

cells were grown. For this reason, many people who

work with mouse ES cells re-derive the cells periodically

to be sure the cells have the potential to differentiate into

or contribute to many different tissues.

Finally, perhaps the most important reason for deriving new ES cell lines rather than simply working with

existing cell lines is that a tremendous amount remains to

be learned during the process of derivation itself. It took

many laboratories more than ten years to ascertain

appropriate conditions for the derivation and growth of

mouse ES cells. Research on the growth and derivation of

ES cells from other mammalian species is only in its early

stages. In fact, only mouse ES cells have the property of

contributing to the germline cell lineage—the most stringent criterion for ES cells. Thus, cells from other species

are referred to as ES-like cells (Pedersen 1994). Further

basic research into the proper conditions to maintain

ES cells from many species is ongoing in an attempt to

understand the factors necessary to generate stable ES

cells. Given that only two successes have been reported

on the derivation of human ES and EG cells, it is likely

that significant basic research into the appropriate conditions to generate stable stem cells will be needed.

Potential Medical Applications of

Human ES Cell and EG Cell Research

Although research into the use of ES and EG cells is still

at an early stage, researchers hope to make a contribution

to disease treatment in a variety of areas. The ability to

elucidate the mechanisms that control cell differentiation

is, at the most elemental level, the promise of human ES

and EG cell research. This knowledge will facilitate the

efficient, directed differentiation of stem cells to specific

cell types. The standardized production of large, purified

populations of human cells such as cardiomyocytes and

neurons, for example, could provide a substantial source

of cells for drug discovery and transplantation therapies

(Thomson et al. 1998). Many diseases, such as

Parkinson’s disease and juvenile-onset diabetes mellitus,

result from the death or dysfunction of just one or a few

cell types, and the replacement of those cells could offer

effective treatment and even cures. 

Substantial advances in basic cell and developmental

biology are required before it will be possible to direct

human ES cells to lineages of human clinical importance.

However, progress has already been made in the differentiation of mouse ES cells to neurons, hematopoietic

cells, and cardiac muscle (Brustle et al. 1997; Deacon et

al. 1998; Shamblott et al. 1998). Human ES and EG cells

could be put to use in targeting neurodegenerative disorders, diabetes, spinal cord injury, and hematopoietic

repopulation, the current treatments for which are either

incomplete or create additional complications for those

who suffer from them.

Use of Human ES Cells and EG Cells in

Transplantation

One of the major causes of organ transplantation and

graft failure is immune rejection, and a likely application

of human ES and EG cell research is in the area of transplantation. Although much research remains to be done,

ES cells derived through SCNT offer the possibility that

therapies could be developed from a patient’s own cells.

In other words, a patient’s somatic cells could be fused

with an enucleated oocyte and developed to the blastocyst

stage, at which point ES cells could be derived for the

development of cell-based therapy. This essentially is an

autologous transfer. Thus, issues of tissue rejection due to

the recognition of foreign proteins by the immune system

are avoided entirely. In addition, research to establish

xenotransplantation (i.e., interspecies transplantation) as

a safe and effective alternative to human organ transplantation is still in its infancy. Alternately, other techniques

that would be immunologically compatible for transplantation purposes could be used to generate stem cells,

such as

1) banking of multiple cell lines representing a spectrum

of major histocompatibility complex (MHC) alleles to

serve as a source for MHC matching, and/or
21

National Bioethics Advisory Commission

2) creating universal donor lines, in which the MHC

genes could be genetically altered so rejection would

not occur, an approach that has been tried in the

mouse with moderate success (NIAID 1999). 

Autologous transplants would obviate the need for

immunosuppressive agents in transplantation as it

would decrease a central danger to transplant patients—

susceptibility to other diseases. Autologous transplants

might address problems ranging from the supply of

donor organs to the difficulty of finding matches

between donors and recipients. Research on ES cells

could lead to cures for diseases that require treatment

through transplantation, including autoimmune diseases such as multiple sclerosis, rheumatoid arthritis,

and systemic lupus erythematosus. These cells also

might hold promise for treating type-I diabetes (Melton

1999; Varmus 1998), which would involve the transplantation of pancreatic islet cells or beta cells produced

from autologous ES cells. These cells would enter the

pancreas and provide normal insulin production by

replacing the failing resident islet cells.

Studies of Human Reproduction and

Developmental Biology

Research using human ES and EG cells could offer

insights into developmental events that cannot be studied directly in the intact human embryo but that have

important consequences in clinical areas, including birth

defects, infertility, and pregnancy loss (Thomson et al.

1998). ES and EG cells provide large quantities of homogeneous material that can be used for biochemical analysis of the patterns of gene expression and the molecular

mechanisms of embryonic differentiation. 

Cancer Therapy

Human ES and EG cells may be used to reduce the

tissue toxicity brought on by cancer therapy (NCI 1999).

Already, bone marrow stem cells, representing a more

committed stem cell, are used to treat patients after highdose chemotherapy. However, the recovered blood cells

appear limited in their ability to recognize abnormal

cells, such as cancer cells. It is possible that injections of

ES and EG cells would revive the complete immune

response to patients undergoing bone marrow transplantation. Current approaches aimed at manipulating the

immune system after high-dose chemotherapy so that 

it recognizes cancer cells specifically have not yet been

successful.

Diseases of the Nervous System

Some believe that in no other area of medicine are the

potential benefits of ES and EG cell research greater than

in diseases of the nervous system (Gearhart 1998;

Varmus 1998). The most obvious reason is that so many

of these diseases result from the loss of nerve cells, and

mature nerve cells cannot divide to replace those that are

lost. For example, in Parkinson’s disease, nerve cells that

make the chemical dopamine die; in Alzheimer’s disease,

it is the cells that make acetylcholine that die; in

Huntington’s disease the cells that make gamma

aminobutyric acid die; in multiple sclerosis, cells that

make myelin die; and in amyotrophic lateral sclerosis, the

motor nerve cells that activate muscles die. In stroke, brain

trauma, spinal cord injury, and cerebral palsy and mental

retardation, numerous types of cells are lost with no builtin mechanism for replacing them.

Preliminary results from fetal tissue transplantation

trials for Parkinson’s disease suggest that supplying new

cells to a structure as intricate as the brain can slow or

stop disease progression (Freed et al. 1999). Yet the difficulty of obtaining enough cells of the right type—that is,

dopamine-producing nerve cells—limits the application

of this therapy. In 1999, scientists developed methods in

animal models to isolate dopamine precursor cells from

the dopamine-producing region of the brain and coax

them to proliferate for several generations in cell culture.

When these cells were implanted into the brains of

rodents with experimental Parkinson’s disease, the animals showed improvements in their movement control

(NINDS 1999). Scientists also have learned to instruct a

stem cell from even a nondopamine region to make

dopamine (Wagner et al. 1999). A large supply of

“dopamine-competent” stem cells, such as ES cell lines,

could remove the barrier of limited amounts of tissue.

(See Exhibit 2-C.) 

Another recent development eventually may provide

treatments for multiple sclerosis and other diseases that

attack the myelin coating of nerves. Scientists have successfully generated glial cells that produce myelin from
22

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

mouse ES cells (Brustle et al. 1999). When these ES cellderived glial cells were transplanted in a rat model of

human myelin disease, they were able to interact with

host neurons and efficiently myelinate axons in the rat’s

brain and spinal cord (Brustle et al. 1999). 

Other diseases that might benefit from similar types

of approaches include spinal cord injury, epilepsy, stroke,

Tay-Sachs disease, and pediatric causes of cerebral palsy

and mental retardation. In mice, neural stem cells already

have been shown to be effective in replacing cells

throughout the brain and in some cases are capable of

correcting neurological defects (Lacorazza et al. 1996;

Rosario et al. 1997; Snyder et al. 1997; Snyder, Taylor,

and Woolfe 1995; Yandava, Billinghurst, and Snyder

1999). Human neural stem cells also have recently been

isolated and have been shown to be responsive to developmental signals and to be willing to replace neurons

when transplanted into mice (Flax et al. 1998). These

recent discoveries of ways to generate specific types of

neural cells from ES cells hold much promise for the

treatment of severe neurological disorders that today

have no known cure.

Diseases of the Bone and Cartilage

Because ES and EG cells constitute a relatively selfrenewing population of cells, they can be cultured to generate greater numbers of bone or cartilage cells than could

be obtained from a tissue sample. If a self-renewing, but

controlled, population of stem cells can be established

in a transplant recipient, it could effect long-term correction of many diseases and degenerative conditions in

which bone or cartilage cells are deficient in numbers or

defective in function. This could be done either by

transplanting ES and EG cells to a recipient or by genetically modifying a person’s own stem cells and returning

them to the marrow. Such approaches hold promise for

the treatment of genetic disorders of bone and cartilage,

such as osteogenesis imperfecta and the various

chondrodysplasias. In a somewhat different potential

application, stem cells perhaps could be stimulated

in culture to develop into either bone- or cartilageproducing cells. These cells could then be introduced

into the damaged areas of joint cartilage in cases of

osteoarthritis or into large gaps in bone that can arise

from fractures or surgery. This sort of repair would have

a number of advantages over the current practice of 

tissue grafting (NIAMS 1999).

Blood Disorders

The globin proteins are essential for transport of oxygen in the blood, with different globins expressed at different developmental stages. The epsilon globin gene is

expressed only in embryonic red blood cells. When this

gene—which is not normally expressed in the adult—is

artificially turned on in sickle cell patients, it blocks the

sickling of the cells that contain sickle cell hemoglobin.

Research involving ES cells could help answer questions

about how to turn on the epsilon globin gene in adult

blood cells and thereby halt the disease process. Stem cell

Exhibit 2-C: Potential Treatment for

Parkinson’s Disease

Parkinson’s disease is a degenerative brain disease

that affects 2 percent of the population over age 70.

Symptoms include slow and stiff movements, problems with balance and walking, and tremor. In more

advanced cases, the patient has a fixed, staring

expression, walks with a stooped posture and short,

shuffling pace, and has difficulty initiating voluntary

movements. Falls, difficulty swallowing, incontinence,

and dementia may occur in the late stages. Patients

often lose the ability to care for themselves and may

become bedridden.

The cause of this illness is a deficiency of the neurotransmitter dopamine in specific areas of the brain.

Treatment with drugs such as levodopa often is

effective in relieving the symptoms. However, as the

disease progresses, treatment often becomes more

problematic, with irregular responses, difficulty

adjusting doses, and the development of side effects

such as involuntary writhing movements. Brain surgery with transplantation of human fetal tissue has

shown promise as therapy.

Stem cell transplantation also may be a promising

therapy for Parkinson’s disease. The injection of

stem cells that can differentiate into brain cells may

offer a means of replenishing neurons that are capable of synthesizing the deficient neurotransmitter. It 

is possible that stem cell transplantation may be 

simpler and more readily available than fetal tissue

transplantation.
23

National Bioethics Advisory Commission

research also may help produce transplantable cells that

would not contain the sickle cell mutation.

Toxicity and Drug Testing

Human stem cell research offers promise for use in

testing the beneficial and toxic effects of biologicals,

chemicals, and drugs in the most relevant species for

clinical validity—humans. Such studies could lead to

fewer, less costly, and better designed human clinical trials yielding more specific diagnostic procedures and

more effective systemic therapies. Beyond the drug development screening of pharmacological agents for toxicity

and/or efficacy, human stem cell research could define

new research approaches for clarifying the complex association of environmental agents with human disease

processes (NIEHS 1999). It also makes possible a new

means of conducting detailed investigations of the underlying mechanisms of the effects of environmental toxins

or mixtures of toxins, including their subtle effects on the

developing embryonic and fetal development tissue

systems.

Transplantable Organs

Several researchers are investigating ways to isolate

AS cells and create transplantable organs that may be

used to treat a multitude of diseases that do not rely upon

the use of embryonic or fetal tissue. Moreover, if it is

found to be possible to differentiate ES cells into specific

cell types, such stem cells could be an important source

of cells for organ growth. For example, recent developments in animals have shown that it may be possible to

create entire transplantable organs from a tissue base in a

manner that would overcome such problems as the limited supply of organs and tissue rejection. Such a development—producing this tissue base by directing the

growth of human embryonic cells—could be a major

breakthrough in the field of whole organ transplantation. 

For example, using tissue engineering methods,

researchers have successfully grown bladders in the laboratory, implanted them into dogs, and shown them to

be functional (Oberpenning et al. 1999). To create the

bladders, small biopsies of tissue were taken from dog

bladders. The biopsied tissue was then teased apart to

isolate the urothelial tissue and muscle tissue, which

were then grown separately in culture (Tanne 1999). The

tissue was then applied to a mold of biodegradable material with the urothelial tissue on the inside and the muscle tissue on the outside. The new organs were

transplanted within five weeks (Tanne 1999).

Dogs that received the tissue-engineered organs

regained 95 percent of their original bladder capacity,

were continent, and voided normally. When the new

organs were examined 11 months later, they were completely covered with urothelial and muscle tissue and had

both nerve and blood vessel growth. Dogs that did not

undergo reconstructive procedures or only received

implants of the biodegradable molds did not regain 

normal bladder function (Oberpenning et al. 1999). This

accomplishment marks the first time a mammalian organ

has been grown in a laboratory. The ability to create new

organs by seeding molds with cells of specific tissue

types would be extremely useful in treating children

with congenital malformations of organs and people who

have lost organs due to trauma or disease (Tanne 1999).

Summary

Currently, human ES cells can be derived from the inner

cell mass of a blastocyst (those cells within the conceptus

that form the embryo proper), and EG cells can be

derived from the primordial germ cells of fetuses. These

cells, present in the earliest stages of embryo and fetal

development, can generate all of the human cell types

and are capable, at least for some time, of self-renewal. A

relatively renewable tissue culture source of human cells

that can be used to generate a wide variety of cell types

would have broad applications in basic research, transplantation, and other important therapies, and a major

step in realizing this goal was taken in 1998 with the

demonstration that human ES and EG cells can be grown

in culture. The clinical potential for these stem cells is

vast—they will be important for in vitro studies of normal

human embryogenesis, human gene discovery, and drug

and teratogen testing and as a renewable source of cells

for tissue transplantation, cell replacement, and gene

therapies.
24

Chapter 2: Human Stem Cell Research and the Potential for Clinical Application

Notes

1 For a summary of scientific progress in this field see Eiseman, E.,

“Human Stem Cell Research,” RAND DRU-2171-NBAC, September

1999, a background paper prepared for the National Bioethics

Advisory Commission.

2 Thomson, J.A., Testimony before NBAC. January 19, 1999.

Washington, DC.

3 Consent to carry out this study was approved by the hospital

ethical committee based on the guidelines on Assisted

Reproductive Technology of the Ministry of Health, Singapore, 

that experimentation of human embryos up to day 14 of 

embryonic growth may be allowed (Bongso et al. 1994).

4 The details of this process are described in a European patent

application (PCT/U397/12919 1997) and in testimony before the

Commission by ACT President Michael West. November 17, 1998.

Miami, FL.

5 Hogan, B., Testimony before NBAC. February 3, 1999.

Princeton, NJ.

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Introduction

I

n the course of attempting to realize the promise of

human embryonic stem (ES) cell and embryonic germ

(EG) cell research to advance basic and applied science as

well as to develop new, life-saving therapies, biomedical

researchers encounter uncertainties in the law as well as

explicit restrictions (including bans on federal research

funding) that were created in response to earlier developments in biomedical science and public policy. At the

same time, provisions also exist in state and federal law

designed to facilitate this field of research and to

establish—or offer models for establishing—appropriate

safeguards to ensure that all efforts to obtain or use stem

cells are carried out in an ethically acceptable way. To

date, three sources of ES or EG cells—cadaveric fetal tissue, embryos remaining after infertility treatments, and

embryos created solely for research purposes using either

in vitro fertilization (IVF) or, potentially, somatic cell

nuclear transfer (SCNT) techniques—have been identified. The goal of this chapter is to examine separately the

legal issues raised by research involving each source of

EG or ES cells, noting as appropriate when common

issues arise.

The Law Relating to Aborted Fetuses 

as Sources of EG Cells

Federal law permits funding of some research with cells

and tissues from the products of elective as well as spontaneous abortions, and state law facilitates the donation

and use of fetal tissue for research. Both state and federal

law set forth several requirements for the process of

retrieving and using material from this source, although

amendments may be needed to federal law in order to

make existing safeguards applicable to stem cell research.

Federal Law Regarding Research Using Cells

and Tissues from Aborted Fetuses

Since as early as the 1930s, American biomedical

research has utilized ex utero fetal tissue both as a medium

and, increasingly, as an object for experimentation

(Gelfand and Levin 1993; Zion 1996). “For many years,

the production and testing of vaccines, the study of viral

reagents, the propagation of human viruses, and the testing of biological products have been dependent on the

unique growth properties of fetal tissue” (Duke 1988,

D112, D114). For example, the 1954 Nobel Prize for

Medicine was awarded to American immunologists who

used cell lines obtained from human fetal kidney cells to

grow polio virus in cell cultures, a key advance in the

development of polio vaccines (Driscoll 1985; Gelfand

and Levin 1993).

In 1972, allegations (some of them quite shocking)

about experiments with fetuses both in and ex utero created an air of controversy (fueled by the greater societal

debate about elective abortion) over the use of fetal tissue

in research.1 When Congress established the National

Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research in 1974, it placed

the topic of research using the human fetus at the top of

the commission’s agenda. Within four months of assuming office, the commissioners were mandated to report

on the subject, with the proviso that the presentation of

their report to the Secretary of the Department of Health,

Education, and Welfare (DHEW)—now the Department

of Health and Human Services (DHHS)—would lift the

moratorium that Congress had imposed on federal

29

The Legal Framework for Federal

Support of Research to Obtain

and Use Human Stem Cells

Chapter Three 3
30

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

funding of research using live fetuses.2 On July 25, 1975,

the National Commission submitted its conclusions and

recommendations, which formed the basis for regulations that the Department issued later that year on

research involving fetuses, pregnant women, and human

IVF (1975). 

General Regulation of Research with Human Beings

Including Fetuses

The 1975 provisions remain as elements of the current federal regulations that aim to protect human subjects participating in research conducted with federal

funds—rules that also are followed on a voluntary basis

by many institutions in the case of research performed

without federal support. The core regulations are set

forth in the Federal Policy for the Protection of Human

Subjects, known as the Common Rule, because the same

regulatory provisions have been adopted by most federal

agencies and departments that conduct or sponsor

research in which human subjects are used. The DHHS

regulations appear in Volume 45, Part 46 of the Code of

Federal Regulations—45 CFR 46. The Common Rule makes

up Subpart A of the DHHS regulations, and additional

protections for special populations of research subjects

appear in three further subparts of 45 CFR 46.

The special provisions applicable to fetal material

appear in Subpart B, which covers research on “1) the

fetus, 2) pregnant women, and 3) human in vitro fertilization” and applies to all DHHS “grants and contracts

supporting research, development, and related activities”

involving those subjects.3 The regulations primarily

address research that could affect living fetuses adversely.

They provide for stringent Institutional Review Board

(IRB) consideration, which is based upon the results of

preliminary studies on animals and nonpregnant women

and on assurances that living fetuses will be exposed only

to minimal risk except when the research is intended to

meet the health needs of the fetus or its mother.4 Specific

restrictions also are imposed on the inclusion of pregnant

women in research activities.

Section 46.210 of Subpart B states that the sole

explicit requirement for research involving “cells, tissues,

or organs excised from a dead fetus” is that such research

“shall be conducted only in accordance with any applicable State or local laws regarding such activities.” 5 Some

analysts have argued that this is the only component of

Subpart B applicable to research in which cells or tissues

from dead abortuses are used in research (Areen 1988).

It appears, however, that even prior to the adoption in

1993 of legislation establishing special rules for using

fetal tissue for transplantation, National Institutes of

Health (NIH) officials had regarded other, general

requirements of Subpart B as applicable to research with

tissue from dead fetuses.6 Specifically, these other provisions exclude researchers from any involvement in the

decision to terminate a pregnancy or in an assessment of

fetal viability and forbid the payment of any inducements

to terminate a pregnancy.7 This dispute over the scope of

Subpart B produces one of the points of uncertainty that

may need to be resolved either through legislation or

official commentary from NIH’s Office for Protection

from Research Risks (OPRR), if investigators using cadaveric fetal tissue to generate human EG cells are to proceed

with confidence and in an ethical fashion.

The Conditions for Federal Support of 

Fetal Tissue Transplantation

In the 1980s, medical scientists began experimenting

with implanting brain tissue from aborted fetuses into

patients with Parkinson’s disease as well as patients with

other neurological disorders. NIH investigators were

among those working in this field, and their protocol to

use fetal tissue for transplantation was approved by an

internal NIH review body. Although the research complied

with Subpart B, then-NIH Director James B. Wyngaarden

decided to seek approval from Assistant Secretary for

Health Robert E. Windom before proceeding.8 In March

1988, Windom responded by declaring a temporary

moratorium on federally funded transplantation research

involving fetal tissue from induced abortions. He also

asked NIH to establish an advisory body to consider

whether such research should be conducted and under

what conditions (Windom 1988). The Human Fetal

Tissue Transplantation Research Panel—composed of

biomedical investigators, lawyers, ethicists, clergy, and

politicians—deliberated until the fall of 1988. Panel

members then voted 19-2 to recommend continued

funding for fetal tissue transplantation research under

guidelines designed to ensure the ethical integrity of any

experimental procedures (Adams 1988; Duguay 1992;
31

National Bioethics Advisory Commission

Silva-Ruiz 1998). In November 1989, after the transition

had been made from the Reagan to the Bush administration, DHHS Secretary Louis Sullivan extended the moratorium indefinitely, based upon the position taken by

the minority-voting panel members that fetal tissue

transplantation research would increase the incidence

of elective abortion (Goddard 1996; Robertson 1993).9

Attempts by Congress to override the Secretary’s decision

were not enacted or were vetoed by President Bush.10

On January 22, 1993, immediately after President

Clinton took office, he instructed the incoming Secretary

of DHHS to lift the ban on federal funding for human

fetal tissue transplantation research.11 On February 5,

1993, DHHS Secretary Donna Shalala officially rescinded

the moratorium, and, in March 1993, NIH published

interim guidelines for research involving human fetal tissue transplantation (OPRR 1994). Provisions to legislate

these safeguards were promptly proposed in Congress and

included in the NIH Revitalization Act of 1993, which

President Clinton signed into law on June 10, 1993.12

The 1993 act mirrors most prior statutory and regulatory provisions on research involving tissue from dead

fetuses.13 In general, the Revitalization Act states that any

tissue from any type or category of abortion may be used

for research on transplantation, but only for “therapeutic

purposes.” Most agree that this means that research on

transplantation that has as its goal the treatment of disease is covered by the act, but that basic laboratory

research—which only tangentially can be described as

having a therapeutic purpose—would not be covered.

Under all conditions, the investigator’s research scope is

not, however, unfettered. First, research activities in this

area must be conducted in accordance with applicable

state and local law. The investigator also must obtain a

written statement from the donor verifying that a) she is

donating fetal tissue for therapeutic purposes, b) no

restrictions have been placed on who the recipient will

be, and c) the donor has not been informed of the identity of the recipient. Further, the attending physician

must sign a statement affirming five additional conditions

of the abortion, aimed at insulating a woman’s decision to

abort from her decision to provide tissue for fetal

research. Finally, the person principally responsible for

the experiment must also affirm his or her own knowledge

of the sources of tissue, that others involved in the research

are aware of the tissue status, and that the researcher had

no part in the abortion decision or its timing.

The statute provides significant criminal penalties for

violation of four prohibited acts: 1) purchase or sale of

fetal tissue “for valuable consideration” beyond “reasonable payments [for] transportation, implantation, processing, preservation, quality control, or storage...,” 

2) soliciting or acquiring fetal tissue through the promise

that a donor can designate a recipient, 3) soliciting or

acquiring fetal tissue through the promise that the recipient will be a relative of the donor, or 4) soliciting or

acquiring fetal tissue after providing “valuable consideration” for the costs associated with the abortion itself.14

Research of the type conducted by Gearhart and his

colleagues at The Johns Hopkins University, in which primordial germ cells were obtained from the gonadal ridge

of human fetuses that had been aborted five to nine

weeks after fertilization, arguably is not covered by the

fetal tissue transplantation provisions of the 1993 NIH

Revitalization Act, because these fetal cells are intended

to be cultured and used in laboratory experiments, not

transplanted. Nevertheless, if such research were federally

supported, it could be subject to the requirements of

Subpart B of 45 CFR 46—both the general limitations of

§ 46.206 (separating the investigators from the abortion

process and forbidding payments for pregnancy termination) and the special requirements of § 46.210 for activities involving cells and tissues from dead fetuses.

Someday, with the advancement of knowledge about cell

differentiation and the like, EG cells derived from dead

fetuses may be linked more directly or indirectly with

transplantation, at which point the 1993 Act would

arguably become applicable.15 In anticipation of that day,

and in order to achieve simplicity in the meantime by

applying the same rules to all federally supported

research with fetal remains, whether or not for transplantation, it would appear desirable to amend the law to

clarify that the safeguards of the 1993 Act apply to

research in which EG cells are obtained from dead

fetuses after a spontaneous or elective abortion.
32

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

State Law Regarding Using Aborted Fetuses 

as Sources of Stem Cells

As recognized by federal statutes and regulations,

state law governs the manner in which cells and tissues

from dead fetuses become available for research, principally by statutes, regulations, and case law on organ

transplantation. The most basic legal provisions lie in the

Uniform Anatomical Gift Act (UAGA), which was first

proposed in 1968 and rapidly became the most widely

adopted uniform statute. While the UAGA is largely consistent with relevant federal statutes and regulations and

should facilitate researchers obtaining cadaveric fetal

tissue, a number of states have adopted other statutes

that limit or prohibit certain types of research with fetal

remains.

Laws Facilitating Donation of Fetal Material 

for EG Cell Research: The UAGA 

The UAGA is relevant not only because federal

statutes and regulations explicitly condition funding for

research with fetal tissue on compliance with state and

local laws, but also because the act applies when EG cell

research using fetal tissue does not receive federal funding. The original version of the UAGA was approved by

all 50 states and the District of Columbia; a 1987 revision

has been enacted by 22 states (Zion 1996).16 The act

establishes a system of voluntary donation of “anatomical

gifts” for transplantation, education, and research. It was

intended to make it easier for people to authorize gifts of

their own body (or parts thereof) through a simple

“donor card” executed before the occasion arose, as well

as to allow donations to be made with the permission of

the next-of-kin, following an order established by the

statute. The revised UAGA includes “a stillborn infant or

fetus” in the definition of “decedents,”17 for whom

parental consent is determinative.18 The UAGA also provides that “neither the physician or surgeon who attends

the donor at death nor the physician or surgeon who

determines the time of death” may be involved in the

team that will use the organs removed from the decedent.19

This section, although it may be waived, seems comparable to the separation that the 1993 NIH Revitalization

Act and Subpart B of the DHHS regulations required

between the research team and any physicians involved

in terminating a pregnancy, determining fetal viability, or

assisting in the clinical procedure during which fetal

tissue is derived for research purposes.20

However, federal law restricts the procedures authorized by the UAGA in one area.21 The UAGA permits

donors to designate recipients—including individual

patients—of anatomical gifts. The stricter provisions of

the NIH Revitalization Act (which prohibits a donor from

having knowledge of an individual transplant recipient)

could override this state law in the case of federally supported fetal tissue transplantation, but the issue might

not arise regarding stem cell research for two reasons.

First, such research does not involve transplantation

(and hence at this time is not relevant to the NIH

Revitalization Act). Second, according to the Revitalization Act, the only recipient who may be designated by

the parents of a dead fetus would be a stem cell

researcher or research institution.

Laws Restricting Use of Donated Fetal Material 

for EG Cell Research

At present, 24 states do not have on their books any

statutes “specifically addressing research on embryos or

fetuses,” 22 and the restrictions in most of the remaining

states principally involve embryos remaining after infertility treatments and limitations aimed at discouraging

therapeutic abortions. For example, in 12 states, the law

applies only to research with fetuses prior or subsequent

to an elective abortion.23 Six states ban research that

involves aborted fetuses or their organs, tissues, or

remains,24 which could cause difficulties for researchers

using stem cell lines derived from aborted fetuses “if cell

lines are considered ‘tissue.’”25 Six other states permit

fetal research when the fetus is deceased, but mandate

that the donor must provide consent,26 although none

“specifically address[es] the type of information that

must be provided to the progenitors before they are

asked for consent.”27 In Pennsylvania, investigators using

fetal tissue and recipients of the tissue are required to be

informed if the tissue was procured as a result of stillbirth, miscarriage, ectopic pregnancy, abortion, or some

other means.28

In order to diminish the impact that the potential use

of a fetus in research might have on the decision to abort,

states have enacted many restrictions on payment for
33

National Bioethics Advisory Commission

fetal remains. The broadest prohibitions appear as part of

state statutes regulating or prohibiting fetal research.

Bans on sale vary in their terminology—an “aborted

product of conception,”29 an “aborted unborn child or the

remains thereof,”30 an “aborted fetus or any tissue or

organ thereof,”31 or an “unborn child”32 —and exist both

in states that permit research on a dead fetus with the

mother’s consent33 and in those where it is illegal to conduct research upon any aborted product of conception.34

The bans on commercialization have a number of

interesting twists. Rhode Island outlaws the selling of an

embryo or fetus for purposes that violate the statute

(such as research on living embryos or fetuses), but

apparently allows payment to the mother for allowing a

dead fetus to be used in research, because such research

is permissible.35 Minnesota prohibits the sale of living

fetuses or nonrenewable organs but explicitly permits

“the buying and selling of a cell culture line or lines taken

from a [dead fetus].”36

The most widely adopted prohibitions on commercialization of fetal remains are those in Sections 10(a) and

(b) of the 1987 revision of the UAGA, which prohibit the

sale or purchase of any human body parts for any consideration beyond that necessary to pay for expenses

incurred in the removal, processing, and transportation

of the tissue.37 On the federal level, what is in essence the

same proscription is included both in the 1993 NIH

Revitalization Act, which bars the acquisition or transfer

of fetal tissue for “valuable consideration” with the same

exceptions,38 and in the National Organ Transplant Act of

1984 (NOTA), which prohibits the sale of any human

organ for “valuable consideration for use in human transplantation”39 if the sale involves interstate commerce.40

(In 1988, Congress amended NOTA to include fetal

organs within the definition of “human organ,” in order

to foreclose the sale of fetal tissue as well.41) Yet both federal statutes could be interpreted to apply only to sales

for transplant or therapeutic purposes, not laboratory

research. Moreover, the definition of reasonable processing fees in the federal law (and by extension, the UAGA)42

is arguably too vague, “leav[ing]...room for unscrupulous

tissue processors to abuse the law” (Goddard 1996, 394).

If special provisions are adopted to govern federal

support of research with fetal material to create human

EG cell lines, it would seem advisable to ensure that the

provisions lay out more clearly what payments may be

made to whom and on what basis for fetal cells and tissues.

The state statutes regulating fetal research have been

challenged in several court cases. Generally, limitations

have been approved as they relate to live fetuses or to the

disposal of aborted fetuses.43 A few cases have dealt with

restrictions on research with dead fetuses or fetal

remains. In 1978, Louisiana adopted a statute forbidding

virtually all experimentation involving a living fetus (“a

live child or unborn child”) that was not “therapeutic” to

that child, a ban it expanded in 1981 to encompass

research with aborted fetal tissue as well.44 Plaintiffs who

argued that the prohibition on research burdened their

right of privacy challenged the law.45 Agreeing, the federal district court concluded that the ban on research did

not further the state’s compelling interest in protecting

the health of the woman, nor did the state’s interest in the

potential life of the unborn continue past the death of the

fetus.46 Finally, the district court addressed the statute’s

vagueness, noting that it was not possible, ex utero, to

distinguish between fetal and maternal tissue and the

products of spontaneous and induced abortions.47 On

appeal, the Fifth Circuit ignored the district court’s

analysis entirely, finding instead that the term “experiment” as used in the statute’s prohibition against fetal

experimentation was unconstitutionally vague.48

The Law Relating to Embryos 

as Sources of ES Cells

Turning to the second source of human ES cells—

embryos created through IVF—one finds that in contrast

to the regulatory complexity of the federal and state laws

governing research using fetal tissue, the legal framework

for research using human embryos is relatively straightforward. With the exception of a few state statutes, no

viable regulatory system exists to guide or control the

practice of human embryo research in the United States.49

Regarding federally supported scientists, law prohibits

such experimentation, while research conducted in the

private sector takes place without any federal medical or

bioethical oversight specific to the human embryo.50 The

central issue raised by existing law is whether the recent
34

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

scientific developments are important enough to justify

modifying, in part, the current blanket ban on federal

support by creating a limited exception for certain types

of human stem cell research.

Federal Law Regarding Research Using Cells

and Tissues from Human Embryos

Federal law regarding research using human embryos

by investigators employed or funded by the federal government may best be understood by reviewing Subpart B

of the DHHS policy on the protection of human subjects

and the rider that has been attached for several years to

the DHHS appropriation, most recently in the Omnibus

Consolidated and Emergency Supplemental Appropriations

Act for Fiscal Year 1999 (OCESAA).51

The former, which continues to provide a basic

framework for research, even though reasons exist to

question its applicability, originated in concerns about

research on the human fetus, but it also applies to “grants

and contracts supporting research, development, and

related activities involving...human in vitro fertilization.”52

At the time these provisions were first promulgated, IVF

was still an experimental technique: The birth in England

of Louise Brown, the first so-called test tube baby, did not

occur until 1978. Recognizing that NIH scientists and

others would wish to pursue research on IVF and the earliest stages of human development, the regulations provided that “no application or proposal involving human

in vitro fertilization may be funded by the Department

[until it] has been reviewed by the Ethical Advisory

Board and the Board has rendered advice as to its acceptability from an ethical standpoint.”53 In 1977, NIH

received an application from an academic researcher for

support of a study involving IVF. After the application

had undergone scientific review within NIH, it was forwarded to the Ethics Advisory Board (EAB) appointed by

Joseph Califano, then Secretary of DHEW. At its May

1978 meeting, the EAB agreed to review the research proposal. With the increased public interest that followed

the birth of Louise Brown that summer, Secretary

Califano asked the EAB to study the broader social, legal,

and ethical issues raised by human IVF. On May 4, 1979,

in its report to the Secretary, the EAB concluded that

federal support for IVF research was “acceptable from an

ethical standpoint” provided that certain conditions were

met, such as informed consent for the use of gametes, an

important scientific goal “not reasonably attainable by

other means,” and not maintaining an embryo “in vitro

beyond the stage normally associated with the completion of implantation (14 days after fertilization)” (DHEW

EAB 1979, 106, 107). No action was ever taken by the

Secretary with respect to the board’s report; for other reasons, the Department dissolved the EAB in 1980.

Because it failed to appoint another EAB to consider

additional research proposals, DHEW effectively forestalled any attempts to support IVF, and no experimentation involving human embryos was ever funded pursuant

to the conditions set forth in the May 1979 report or

through any further EAB review.

Because the Revitalization Act of 1993 effectively

ended the de facto moratorium on IVF and other types of

research involving human embryos54 by nullifying the

regulatory provision that mandated EAB review,55 NIH

Director Harold Varmus convened the Human Embryo

Research Panel to set forth standards for determining

which projects could be funded ethically and which

should be considered “unacceptable for federal funding.”56 The panel identified several areas of potential

research activity that it considered ethically appropriate

for federal support, including studies involving the

development of ES cells, though only with embryos

resulting from IVF or clinical research that have been

donated with the consent of the progenitors. The most

controversial aspect of the report was its conclusion that

it might be ethical to allow researchers to create human

embryos for certain research purposes.57

In September 1994, the panel submitted its report to

the Advisory Committee to the Director (ACD) of NIH,

which formally approved the recommendations and

transmitted them to Varmus on December 1, 1994. The

following day, pre-empting NIH’s response, the President

declared that federal funds should not be used to support

the creation of human embryos for research purposes

and directed that NIH not allocate any resources for

such requests.58 Thereafter, Varmus decided to implement the panel’s recommendations not proscribed by the

President’s directive, concluding that NIH could begin to

fund research activities involving “surplus” embryos
35

National Bioethics Advisory Commission

(Feiler 1998). Before any funding decisions could be

made, however, Congress attached a rider to that year’s

DHHS appropriations bill that stipulated that none of the

funds appropriated could be used to support any activity involving “1) the creation of a human embryo or

embryos for research purposes; or 2) research in which a

human embryo or embryos are destroyed, discarded, or

knowingly subjected to risk of injury or death greater

than that allowed for research on fetuses in utero under

45 CFR 46.208(a)(2) and section 498(b) of the Public

Health Service Act (42 USC 289g(b)).”59

When the question arose of whether to provide federal funding for human ES cell research using IVF

embryos remaining from infertility treatments, Varmus

sought the opinion of Harriet Rabb, DHHS General

Counsel, regarding the effect of the prohibition in the

current appropriations rider. Rabb reported to Varmus

that the OCESAA does not prevent NIH from supporting

research that uses ES cells derived from this source

because the cells themselves do not meet the statutory,

medical, or biological definition of a human embryo

(NIH OD 1999).60

Having concluded that NIH may fund internal and

external research that utilizes but does not create human

ES cells, NIH has delayed actual funding until an Ad Hoc

Working Group of the ACD develops guidelines for the

ethical research in this area.61 The working group began

its deliberations in early 1999 and completed draft guidelines on April 8, 1999, which are still undergoing internal review and public comment.62

In addition to these guidelines, ES cell research that

was supported by federal funds and directly involved

human embryos might arguably be subject to the

requirements of both Subpart A (the Common Rule)

and Subpart B of 45 CFR 46—that is, the research would

be required to meet general and specific substantive

requirements, would have to be approved by the IRB of

the investigator’s institution, and might have to undergo

further review at the national level. We use the word

“arguably” because OPRR has provided no definitive

guidance regarding such an interpretation. Indeed, in

response to the Commission’s inquiry of May 18, 1999,

OPRR acknowledged that “although Subpart B does not

apply to research involving a human embryo, per se, it

does apply to research that involves the process of in vitro

fertilization. An embryo formed by a means that does not

involve in vitro fertilization would not be subject to

Subpart B.”63 Because no other guidance is provided, we

are left to interpret whether embryos (which are not

defined in regulation) are human subjects and therefore

protected by Subpart B.

Subpart A, which contains the basic requirements for

IRB review, informed consent, privacy protection, and

the like, aims to protect a “human subject,” defined as “a

living individual about whom an investigator...obtains

(1) data through intervention or interaction....”64 This

definition creates uncertainties about whether the

Common Rule applies to embryo research, the derivation

of ES cells, and research involving successor stem cells

from embryonic sources that require resolution. This is

another point upon which a clearer, more accessible

interpretation is needed from OPRR if investigators and

IRBs are to proceed with confidence regarding a range of

stem cell research activities involving human embryos.

Assuming that the DHHS regulations apply, the special

requirements of Subpart B also would be applicable,

because (as previously described) NIH has long taken the

position that human IVF research, which is clearly

encompassed in Subpart B, encompasses any DHHSfunded research involving human embryos not 

in utero. This would mean not only that another EAB

could be impaneled by the Secretary pursuant to 45 CFR

§ 46.204, but also that special responsibility would fall

on investigators and IRBs under 45 CFR § 46.205.65 In

addition, special standards would have to be met under

45 CFR § 46.206, including mandates for prior studies

involving animals and ensuring the least possible risk.

The newly revised 45 CFR 46, Subpart B (not yet finalized) makes no substantive changes that would affect

these requirements.66

State Law Regarding Research Using Cells 

and Tissues from Human Embryos 

State legislatures have apparently been more concerned about regulating and restricting research using

human fetuses or their remains instead of addressing

research involving laboratory manipulation of human

gametes and early stage embryos. Nonetheless, although
36

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

the statutes usually ignore issues (other than commercialization) specific to IVF (Robertson 1990), some

could be construed broadly enough to encompass a

range of experimental activities involving IVF, including

cryopreservation, pre-implantation screening, gene therapy, twinning, cell line development, and basic research

(Coleman 1996). The latter two are of obvious relevance

to creating stem cell cultures from embryonic sources.

States that regulate cell line development from human

embryos either prohibit the practice entirely or restrict it

substantially (Coleman 1996). “All ten states that prohibit

embryological research have vaguely worded statutes

which could encompass cell line development if the

statutes were interpreted broadly...[although] some

[activity] could be characterized as non-experimental,

thus removing it from the scope of experimentation

bans” (Coleman 1996, 1358). Issues inherent in cell line

development will include the potential for restrictions on

downstream commercialization and uncertainty over the

extent to which gamete donors must be informed about

the nature of and potential commercial uses of the biological materials they donate (Coleman 1996).

Basic research typically involves precommercial scientific activity designed to explore biological processes or to

understand genetic and cellular control mechanisms. As

noted previously, 24 states and the District of Columbia

do not restrict research involving fetuses or embryos.67 Of

the remaining 26 states that regulate embryo or fetal

research in one form or another, basic embryological

research is prohibited or restricted in 10 (Feiler 1998).

Although the degree of regulation of experimental use of

embryos under the New Hampshire statute is unlikely to

impair ES cell research in that state,68 the remaining nine

states have legislated more broadly, effectively banning 

all research involving in vitro embryos, with penalties

mandated in some states, including civil fines and

imprisonment.69

The subject of commercialization is a potentially

important one, affecting both researchers who must

acquire embryos from for-profit IVF clinics or other

sources and downstream users who may develop derivative, commercial applications from basic embryological

and stem cell research. Currently, five states prohibit payment for IVF embryos for research purposes.70 Eight

additional states prohibit payment for human embryos

for any purpose.71 Five states apply ambiguous restrictions that may or may not prohibit sale of embryos,

depending upon interpretation or, in some cases, action

by state officials.72 More troubling, some statutes could be

interpreted to prevent payment for ES cell lines derived

from human embryos (Coleman 1996), although “it is

possible that because a cell line is new tissue produced

from the genetic material of, but not originally a part of,

the embryo, laws proscribing the sale of embryonic

tissue may not apply.”73 In line with NOTA and the

1987 revisions of the UAGA, state statutes on organ

transplantation now typically prohibit sale of human

organs or parts, but none include language likely to

impede research involving human embryos.

The Law Relating to Deriving 

Stem Cells from Organisms Created

Through Cloning

The third potential source of human ES cells would

involve the use of cloning—that is, SCNT. One possible

use of SCNT would be to derive ES cells themselves, thus

avoiding the need for embryos. If such a transfer directly into an enucleated stem cell were to be successful,

the therapeutic potential of creating cells and tissues

for autologous transplantation might be realized without any of the ethical and regulatory problems associated with the creation of embryos.

At present, however, the method for creating human

ES cells through SCNT, which has been announced by

one scientific team (although not yet published in a scientific journal), involves inserting a somatic cell nucleus

into an enucleated oocyte, which, if it then developed,

would become a blastocyst from which ES cells would be

derived. This approach creates two problems. First, if the

blastocyst were characterized as a human embryo (albeit

one created asexually rather than by uniting egg and

sperm in vitro), then the prohibition on federal funding

(as well as the restrictions on embryo research in several

states) would come into play. Second, the process of carrying out SCNT using human cells has been outlawed by

at least two states and may or may not be eligible for

federal funding. On March 4, 1997, shortly after the 
37

National Bioethics Advisory Commission

initial announcement that the Roslin Institute had 

succeeded in creating Dolly, the cloned sheep, the Office

of the White House Press Secretary released a

“Memorandum for the Heads of Executive Departments

and Agencies,” in which the President stated that

Federal funds should not be used for cloning of

human beings. The current restrictions on the use of

Federal funds for research involving human embryos

do not fully assure this result. In December 1994, I

directed the National Institutes of Health not to fund

the creation of human embryos for research purposes. The Congress extended this prohibition in FY

1996 and FY 1997 appropriations bills, barring the

Department of Health and Human Services from supporting certain human embryo research. However,

these restrictions do not explicitly cover human

embryos created for implantation and do not cover all

Federal agencies. I want to make it absolutely clear

that no Federal funds will be used for human cloning.

Therefore, I hereby direct that no Federal funds shall

be allocated for cloning of human beings.74

On June 9, 1997, the President received NBAC’s

report entitled Cloning Human Beings and announced his

acceptance of its recommendations, which included a

moratorium on publicly or privately funded research to

create a child through SCNT but not on laboratory

research using the technique. A number of bills have

been introduced in Congress to achieve this result—as

have other bills that would enact a broader prohibition—

but no federal legislation has been adopted. On February

9, 1998, responding to one of those bills (S. 1601, The

Human Cloning Prohibition Act), the Executive Office of

the President released a Statement of Administration

Policy, which provides in part that

the Administration supports amendments to S. 1601

that would...permit somatic cell nuclear transfer

using human cells for the purpose of developing stem

cell (unspecified cells capable of giving rise to specific cells and tissues) technology to prevent and

treat serious and life-threatening diseases and other

medical conditions, including the treatment of cancer, diabetes, genetic disorders, and spinal cord

injuries and for basic research that could lead to

such treatments.75

This statement does not, however, have the force or

effect of a Presidential Directive or Executive Order and

does not modify the March 1997 Presidential Directive

prohibiting funding for human cloning by federal agencies. The resulting uncertainty must be resolved, taking

into account the ethical analysis presented in the next

chapter.

Summary

As described in Chapter 2, the development of human 

ES and EG cell lines represents an important advance in

biomedicine that promises not only to expand basic scientific understanding but also to improve health and

extend life for millions of patients. Even the greatest supporters of this new field recognize, however, that current

methods of deriving EG and ES cells from cadaveric fetal

tissue and embryos remaining after infertility treatments

raise significant ethical issues. Further ethical analysis,

which appears in the next chapter of this report, is needed

before conclusions can be reached about the goals and

principles that should guide policymaking in this field.

Federal law permits the funding of some research that

uses tissue from dead fetuses following spontaneous or

elective abortion, provided the researchers follow safeguards that aim to separate the decision to abort from the

decision to donate material for research, to ensure appropriate consent, and to avoid commercialization of fetal

material. The UAGA, which in every state facilitates the

process of donating bodies and organs for research as

well as transplantation, treats fetuses like other cadavers;

the latest version of the statute imposes special conditions on the donation of fetal remains and reinforces the

prohibition in federal law against paying for organ

donation. The legal framework identified by these

statutes is thus favorable to research in which EG cells

would be derived from fetal tissue. Some questions

remain, however, about the applicability of some of the

statutes—for example, the principal set of federal safeguards appears in a statute dealing with fetal tissue transplantation, and EG cell research does not now, and may

never, involve directly the transplantation of tissue or

cells from a fetus to a patient. Therefore, to overcome the

uncertainties and ensure that ethical safeguards are
38

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

understood to be applicable to fetal stem cell research,

statutory modification and regulatory clarification are

desirable. 

Confusion also is caused by restrictions and bans in

several states on research use of the products of induced

abortions; although these statutes seem aimed principally at research with living fetuses, some have—or may

be read to have—broader reach. The common theme of

these statutes—as in the law on federally funded

research—is to erect a significant barrier between a

woman’s decision to abort a fetus and the separate question of whether fetal remains will be donated for

research. To support that barrier, many states employ

consent requirements and prohibit payment for fetal

remains, so that such material does not become commercialized and thus inappropriately influence the abortion

decision. 

The picture is clearer but less favorable to research in

the area of embryos remaining after infertility treatments.

In addition to restrictions and even outright prohibitions

in the law of a number of states, riders to DHHS appropriation statutes in recent years rule out the use of these

funds in any process in which human embryos are

created for research or are destroyed or subject to a risk

of injury. Once it has developed special guidelines to

ensure that investigators will safeguard the ethics of the

process, NIH will fund suitable research projects using

human ES cells derived from IVF embryos, although it

will not fund the derivation process itself. This position

has been denounced by many members of Congress who

supported the ban on federal funding of research with

embryos and who believe that however the statutory

language may be read, its intent clearly is to prohibit

research that depends upon the prohibited acts.

The questions raised by this disagreement go beyond

interpretation of the language and intent of the DHHS

appropriations rider. First, is the justification for research

using human ES cells compelling enough to permit an

exception to the ban on federal funding for embryo

research? Second, can an exception be crafted in a way

that continues to give appropriate weight to the values

that underlie the ban in the first place? And third, is the

justification for using ES cells strong enough to permit

funding of the process of deriving these cells from IVF

embryos remaining after infertility treatments? Answers

to these questions will require evaluation of the scientific

and medical aspects of human ES cell research that are

described in Chapter 2 in the context of the ethical considerations that are discussed in Chapter 4. 

Notes

1 Proposed guidelines for fetal tissue research were released by

NIH and DHEW in 38 Fed. Reg. 31,738 (1973) (Gelfand and 

Levin 1993).

2 See National Research Act, Public Law 93-348, Section 201(a),

88 Stat. 348 (1974).

3 45 CFR § 46.201(a) (1997). “The purpose of this subpart [is]

to...assure that [applicable research] conform[s] to appropriate 

ethical standards and relate[s] to important societal needs” 

(Ibid. at § 46.202).

4 The portions of Subpart B dealing with research on living fetuses

were re-enforced by the Human Research Extension Act of 1985.

The act directs that no federally supported research may be conducted on a nonviable living human fetus ex utero or on a living

human fetus ex utero for whom viability has not been determined,

unless a) the research or experimentation may enhance the health,

well-being, or probability of survival of the fetus itself; or b) will

pose no added risk of suffering, injury, or death to the fetus where

the research or experimentation is for “the development of important biomedical knowledge which cannot be obtained by other

means.” In either instance, the degree of risk must be the same for

fetuses carried to term as for those intended to be aborted (42 USC

§ 289g 1998).

5 On May 20, 1998, DHHS released for public comment proposed

revisions of Subpart B, most of which relate to research with living

fetuses. In these revisions, § 46.210 would become § 46.206,

which would retain the requirement that research with material

from a dead fetus would have to conform to state law. The revised

regulation would add that any living individual who becomes personally identified as a result of research on dead fetal or placental

material must be treated as a research subject and accorded the

protections of the federal Common Rule.

6 During the period of 1987–92, the NIH Office of Science Policy

repeatedly stated that NIH applies Subpart B broadly to a range of

fetal research activities. For example, in a 1988 memorandum,

NIH Director James B. Wyngaarden informed Assistant Secretary

for Health Robert E. Windom that “[a]s you know, the NIH conducts all human fetal tissue research in accordance with Federal

Guidelines (45 CFR 46),” and provided a 1987 summary of fetal

tissue research at NIH that stated that “NIH-supported human fetal

tissue research is conducted in compliance with all Federal...

regulations regarding the use of human fetal tissue. These regulations include restrictions on tissue procurement [Subpart B] that

are intended to prevent possible ethical abuses” (NIH 1987;

Memorandum from James B. Wyngaarden to Robert E. Windom,

February 2, 1988).
39

National Bioethics Advisory Commission

7 45 CFR §§ 46.206 (a)(3) and 46.206(b)(1997).

8 “Although such approval was not required, the Assistant

Secretary was consulted because of the scientific and ethical 

implications of the study” (Ryan 1991, 687).

9 Letter from Louis Sullivan to William Raub, November 2, 1999.

10 See H.R. 2507, 102d Cong., 1st Sess. (1991) (amending Part G

of Title IV of the Public Health Service Act). See also H.R. 5495,

102d Cong., 2nd Sess. (1992) (amending Part G of Title IV of the

Public Health Service Act and incorporating the establishment of a

federally operated national tissue bank as provided by Exec. Order

No. 12,806 [1992]). During this period, in an apparent attempt to

find an alternative to fetal tissue derived from elective abortion, 

the administration established (without success) a tissue bank to

collect fetal tissue for research from ectopic pregnancies and 

miscarriages. Exec. Order No. 12,806, 57 Fed. Reg. 21,589 (1992).

Because spontaneously aborted tissue may contain viral infections

or pathological defects, the use of ectopic and miscarried abortuses

is disfavored for transplantation and most other research. In

October 1992, a consortium of disease advocacy organizations 

filed suit against DHHS Secretary Sullivan, alleging that the 

Hyde Amendment, which bars federal funding for abortions,

Departments of Labor, Health, Education, and Welfare

Appropriations Act of 1977, Public Law 94-439, did not apply 

to research on and transplantation of fetal tissue. The plaintiffs

argued, moreover, that the fetal tissue transplantation research 

ban was beyond the Department’s statutory authority under the

law (Bell 1994). 

11 See 58 Fed. Reg. 7457 (1993).

12 The administration’s policies on fetal tissue transplantation did

not entirely quell public controversy or congressional interest

(GAO 1997). 

13 The policy initiated by President Clinton in 1993 and formalized in the 1993 NIH Revitalization Act is in line with the position

taken in many other countries that the use of fetal tissue from 

elective abortions in therapy for people with conditions such as

Parkinson’s disease is acceptable. As with U.S. laws and regulations, international guidelines emphasize the need to separate the

decision to terminate pregnancy from the decision to donate fetal

tissue and the need for informed consent for the donation. See

Knowles, L.P., 1999, “International Perspectives on Human

Embryo and Fetal Tissue Research.” This background paper was

prepared for NBAC and is available in Volume II of this report.

14 42 USC § 289g-2(a)-(c) (1997). But see Goddard (1996).

15 DHHS General Counsel Harriet Rabb apparently believes that

research of the type conducted by Gearhart is already sufficiently

connected to transplantation to be subject to the NIH

Revitalization Act, though she does not explain how she reached

that conclusion. In a January 15, 1999, memorandum to NIH

Director Varmus, Rabb concluded that “[t]o the extent human

pluripotent stem cells are considered human fetal tissue by law,

they are subject to...the restrictions on fetal tissue transplantation

research that is conducted or funded by DHHS, as well as to 

the federal criminal prohibition on the directed donation of fetal

tissue.” Rabb examined the definition of “fetal tissue” at 42 USC

289g-1(g) which defines it as “tissue or cells obtained from a dead

human embryo or fetus after a spontaneous or induced abortion,

or after a stillbirth” and observed that “some stem cells, for example those derived from the primordial germ cells of non-living

fetuses, would be considered human fetal tissue for purposes of

[federal law].” Having concluded that primordial germ cells

extracted from nonliving fetuses are a type of fetal tissue, the

General Counsel went on, without further explanation, to apply

the prohibition on sale of fetal tissue, the firewall restrictions, and

the donative limitations stipulated in the NIH Revitalization Act, 

as well as the requirements of 45 CFR § 46.210.

16 National Conference of Commissioners on Uniform State Laws

(NCCUSL), A Few Facts About the Revised Uniform Anatomical Gift

Act, 1987.

17 Uniform Anatomical Gift Act (UAGA) § 1(3). But see Zion

(1996): “UAGA...does not differentiate between a fetus donated

from a miscarriage or one given through an elective abortion.

Presumably, either type of donation is included, but a certain

determination is difficult” (1293).

18 Under § 3 of the UAGA, the first two categories of individuals

who may consent to donate are a spouse or adult child of the 

decedent, which would be irrelevant in the case of a fetus, thus

giving priority to the next class, the parents. Usually, permission

from any member of a class is adequate, unless a majority of the

class objects, though as revised, the “UAGA makes the mother’s

consent determinative unless the father objects, and...does not 

provide for notice to the father” (Gelfand and Levin 1993, 679).

Gelfand and Levin contrast this UAGA provision with 45 CFR 

§ 46.209(d), which requires the father’s consent unless his identity

or whereabouts “cannot reasonably be ascertained” or he is “unavailable” to consent; however, these provisions apply only “until it has

been ascertained whether or not a fetus ex utero is viable,” and do 

not apply to donation of a dead fetus or fetal remains.

19 UAGA § 8(b).

20 See, for example, 45 CFR § 46.206(a)(3) (“Individuals engaged

in the activity [of research] will have no part in: (i) Any decisions

as to the timing, method, and procedures used to terminate the

pregnancy, and (ii) determining the viability of the fetus at the 

termination of the pregnancy”); see also Zion (1996): “These provisions create a ‘Chinese Wall’ between the individuals effecting the

abortion and those conducting fetal tissue research and transplantation....While this language standing alone would likely preclude

most undue influence, the UAGA also provides for the waiver of

the ‘Chinese Wall’....[R]evision may be necessary” (1294).

21 There are also state laws whose restrictions regarding choosing

tissue recipients are broader, and may have implications for stem

cell research. In Pennsylvania, for example, “No person who consents to the procurement or use of any fetal tissue or organ may

designate the recipient of that tissue or organ, nor shall any other

person or organization act to fulfill that designation” (18 Pa. Cons.

Stat. Ann. § 3216(b)(5)). This law unintentionally would create the
40

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

situation where an IVF patient could donate her excess embryo 

for stem cell research, but she could specify that it be used by a

particular medical center. She would have to blindly turn it over,

and risk it going to a researcher or entity (such as a for-profit 

company) that she might not approve of. See Andrews, L.B., 1999,

“State Regulation of Embryo Stem Cell Research.” This background

paper was prepared for NBAC and is available in Volume II of this

report.

22 Andrews 1999. 

23 See Ariz. Rev. Stat. Ann. § 36-2302(A) (subsequent); Ark. Stat.

Ann. § 20-17-802 (subsequent); Cal. Health and Safety Code 

§ 123440 (subsequent); Fla. Stat. Ann. § 390.0111(6) (prior or

subsequent); Ind. Code Ann. § 16-34-2-6 (subsequent); Ky. Rev.

Stat. § 436.026 (subsequent); Mo. Ann. Stat. § 188.037 (prior or

subsequent); Neb. Rev. Stat. § 28-346 (subsequent); Ohio Rev.

Code Ann. § 2919.14(A) (subsequent); Okla. Stat. Ann. tit. 63, 

§ 1-735(A) (prior or subsequent); Tenn. Code Ann. § 39-15-208

(subsequent); Wyo. Stat. Ann. § 35-6-115 (subsequent).

24 Ariz. Rev. Stat. Ann. § 36-2302, -2303; Ind. Code Ann. 

§ 1 6.34-2-6; N.D. Cent. Code § 14-02.2-01 to -02; Ohio Rev.

Code Ann. § 2919.14; Okla. Stat. Ann. tit. 63, § 1-735; S.D.

Codified Laws Ann. § 34-23A-17.

25 Andrews 1999. Similarly, Arizona’s statute provides that a 

“person shall not knowingly use any human fetus or embryo, 

living or dead, or any parts, organs or fluids of any such fetus 

or embryo resulting from an induced abortion in any manner”

(Ariz. Rev. Stat. § 36-2302(A)). 

26 Ark. Stat. Ann. § 20-17-802(2); Mass. Ann. Laws ch. 112 

§ 12J(a)(II); Mich. Comp. Laws Ann. § 333.2687 (must also 

comply with state’s version of the UAGA, Mich. Comp. Laws Ann.

§ 333.10101 et seq.); 18 Pa. Cons. Stat. Ann. § 3216(b)(1) 

(mother’s consent valid only after decision to abort has been 

made; no compensation allowed); R.I. Gen. Laws § 11-54-1(d);

Tenn. Code Ann. § 39-15-208(a).

27 Even in the context of research on live fetuses, only New

Mexico’s statute describes the information that must be provided

before consent to research involving a fetus is valid. Under the

New Mexico law, a woman who is asked to participate in research

must be “fully informed regarding possible impact on the fetus”

(Andrews 1999, citing N.M. Stat. Ann. § 24-9A-2(b)). 

28 18 Pa. Cons. Stat. Ann. § 3216(b)(4).

29 Ohio Rev. Code Ann. § 2919.14.

30 Okla. Stat. Ann. § 1-735.

31 N.D. Cent. Code § 14-02.2-01(2); Mo. Stat. Ann. § 188.036(5).

32 Tenn. Code Ann. § 39-15-208 (also prohibits sale of an aborted

fetus); Utah Code Ann. § 76-7-311.

33 Ark. Stat. Ann. § 20-17-802(c); also a crime to possess such

material, § 20-17-802(d).

34 See, for example, Ind. Stat. § 35-46-5-1 (applies both to 

aborted and stillborn fetuses); Ohio Rev. Code Ann. § 2919.14(A);

Okla. Stat. Ann. § 1-735(A).

35 R.I. Geb. Laws § 11-54-1(f).

36 Minn. Stat. Ann. § 145.422(3).

37 Of the 23 states in which organ transplant laws forbid payment,

two appear inapplicable to using fetal remains in stem cell

research: Arizona’s statute defines a decedent to include a stillborn

infant but not a fetus (Ariz. Rev. Stat. § 36-849(1)), and Kentucky

excludes “fetal parts or...any products of the birth or conception”

from its definition of “transplantable organs” that may not be sold

(Ky. Rev. Stat. Ann. § 311.165(5)(b)).

38 42 USC § 289g-2(a) (1997).

39 National Organ Transplant Act (NOTA) 42 USC § 274e(a)

(1997). “Valuable consideration” is defined at 42 USC § 274e(c)(2)

(1997) negatively: “‘valuable consideration’ does not include the

reasonable payments associated with the removal, transportation,

implantation, processing, preservation, quality control, and storage

of a human organ or the expenses of travel, housing, and lost wages

incurred by the donor of a human organ in connection with the

donation of the organ.” A similar definition (excluding donor costs)

is provided in the NIH Revitalization Act at 42 USC § 289g-2(d)(3)

(1997).

40 Because the definition of “interstate commerce” in NOTA is

based upon the Federal Food, Drug and Cosmetic Act, which

defines it as “commerce between any State or Territory and any

place outside thereof,” 21 USC § 321(b), NOTA’s prohibitions

extend to purchasing organs abroad for importation into the United

States. Most countries explicitly prohibit the commercialization of

human fetal tissue. The Canadian Royal Commission on New

Reproductive Technologies stated that the noncommercialization of

reproduction should be considered a guiding principle. The commission recommended that no for-profit trade be permitted in fetal

tissue and that the “prohibition on commercial exchange of fetuses

and fetal tissue extend to tissues imported from other countries”

(1993). This prohibition was intended to prevent the exploitation

of poor women, especially in developing countries, who might be

persuaded to begin and end pregnancies for compensation.

41 Organ Transplants Amendment Act of 1988, 42 USC 

§ 274(e)(c)(1) (1997). The amendment was specifically intended

to prevent the “sale or exchange for any valuable consideration” of

fetal organs and tissue. 134 Cong. Rec. S10, 131 (27 July 1988).

42 As enacted in six states, the statutes prohibit the sale of human

organs but fail to include a definition of “valuable consideration”

that stipulates an exemption for miscellaneous overhead expenses;

sixteen states provide such an exemption (Andrews 1999).

43 See for example, Doe v. Rampton, 366 F. Supp. 189, 194 (D.

Utah 1973) (suggesting in dicta that statute provision prohibiting

research on live fetus may not be otherwise unconstitutional),

vacated and remanded, 410 U.S. 950 (1973) (directing further

consideration in light of Roe); Wolfe v. Schroering, 388 F. Supp. 631,

638 (W.D. Ky. 1974), aff’d in part, rev’d in part on other grounds,

541 F.2d 523 (6th Cir. 1976) (upholding prohibition on experimentation on a viable fetus due to state’s interest in the fetus after

viability); Planned Parenthood Association v. Fitzpatrick, 401 F. Supp.
41

National Bioethics Advisory Commission

554 (E.D. Penn. 1975), aff’d without opin sub nom.; Franklin v.

Fitzpatrick, 428 U.S. 901 (1976) (affirming legitimate state interest

in disposal of fetal remains); Wynn v. Scott, 449 F. Supp. 1302, 1322

(N.D. Ill. 1978) (medical researchers have no fundamental rights

under the Constitution to perform fetal experiments), aff’d on other

grounds sub nom.; Wynn v. Carey, 599 F.2d 193 (7th Cir. 1979)

(upholding state’s rational interest in regulating medicine as to viable

fetus); Leigh v. Olson, 497 F. Supp. 1340 (D.N.D. 1980) (striking fetal

disposal statute as vague where it left “humane disposal” undefined

and required mother to determine method of disposal); Akron v.

Akron Center for Reproductive Health, Inc., 462 U.S. 416 (1983)

(struck down local ordinance that, inter alia, mandated humane and

sanitary disposal of fetal remains, finding the provision impermissibly

vague because it was unclear whether it mandated a decent burial of

the embryo at the earliest stages of formation); Planned Parenthood

Association v. City of Cincinnati, 822 F.2d 1390, 1391 (6th Cir. 1987)

(struck down on other grounds, the court noted in dicta that the

wording used by the municipal code regulating disposal of aborted

fetal tissue might be precise enough to survive scrutiny); Planned

Parenthood of Minnesota v. Minnesota, 910 F.2d 479 (8th Cir. 1990)

(upholding Minnesota’s fetal disposal statute against challenge of

vagueness and infringement of privacy).

44 La. Rev. Stat. Ann. § 40:1299.35.13. See Clapp (1988): “The

Louisiana statute effectively prohibits any research, experimentation, or even observational study on any embryo, fetus, or aborted

fetal tissue. The ban encompasses a range of activities, including

studies of the safety of ultrasound and pathological study of fetal

tissues removed from a woman for the purpose of monitoring her

health. Research on IVF is likewise barred. Since the aborted previable fetus is not living or cannot survive for long, no procedure

performed upon it could be considered ‘therapeutic,’ and therefore

use of this tissue is likewise prohibited. If performed on tissues

from a miscarriage, such experimentation would be acceptable

under the statutory scheme” [footnote omitted] (1076–1077).

45 Margaret S. v. Treen, 597 F. Supp. 636 (E.D. La. 1984), aff’d 

sub nom.; Margaret S. v. Edwards, 794 F.2d 994 (5th Cir. 1986).

See Clapp (1988): The court “specifically note[d] that reproductive

choice was ‘not limited to abortion decisions...but extends to both

childbirth and contraception.’ Prohibiting experimentation on fetal

tissues could deny a woman knowledge that would influence her

own future pregnancies, as well as prohibit procedures of immediate

medical benefit such as pathological examination of tissues. The

court also found that the prohibition curtailed the development and

use of prediagnostic techniques, including amniocentesis. This result

constituted a ‘denial of health care’ and a ‘significant burden’ on

choice made during the first trimester” [footnote omitted]

(1078–1079).

46 Margaret S. v. Treen, 597 F. Supp. 636, 674-75 (E.D. La. 1984).

See Clapp (1988): “The court further suggested the statute would

fail even a rational relation test because it failed to serve its own

stated purpose of treating the fetus like a human being, since it

treated fetal tissue differently from other human tissue” (1079).

47 Margaret S. v. Treen, 597 F. Supp. 636, 675-76 (E.D. La. 1984).

48 Margaret S. v. Edwards, 794 F.2d 994, 999 (5th Cir. 1986). “The

whole distinction between experimentation and testing, or between

research and practice, is...almost meaningless, [such that] ‘experiment’ is not adequately distinguishable from ‘test’...every medical

test that is now ‘standard’ began as an ‘experiment.’” But see Clapp

(1988): “[T]he court hypothesized that the statute was intended ‘to

remove some of the incentives for research-minded physicians...to

promote abortion’ and was therefore ‘rationally related to an

important state interest.’ This language suggests that if the statute

had not been vague, the court would have applied less than strict

scrutiny to a ban on fetal research. The court also implied, in dicta,

that the rationale was based on the ‘peculiar nature of abortion and

the state’s legitimate interest in discouraging’ it, relying on H.L. v.

Matheson, 450 U.S. 398, 411–413 (1981)” (1080). A concurring

opinion “criticized the majority for avoiding the real constitutional

issue raised—that any statutory ban on experimentation would

inevitably limit the kinds of tests available to women and their

physicians and thus could not help but infringe on fundamental

rights” Ibid. at 999–1002 (Williams, J., concurring) (Clapp 1988,

1080). See also Jane L. v. Bangerter, 61 F.3d 1493 (10th Cir. 1995)

(striking down as vague Utah’s criminal prohibition on fetal

research which permitted experimentation aimed at acquiring

genetic information about the embryo or fetus).

49 Members of Congress who have opposed stem cell funding 

maintain that “current law...also specifically covers cells and tissue

obtained from embryos,” citing as applicable 42 USC § 289g1(b)(2)(ii) (“no alternation of the timing, method, or procedures used

to terminate the pregnancy...made solely for the purposes of obtaining the [fetal] tissue”) (Members of the House of Representatives

1999). The apparent basis for this assertion is the definition of

“human fetal tissue” at 42 USC § 289g-1(g) (“for purposes of this

section, the term ‘human fetal tissue’ means tissue or cells obtained

from a dead human embryo or fetus after a spontaneous or induced

abortion”). Two elements render the congressional arguments unpersuasive: 1) neither 42 USC § 289g-1 nor 289g-2 is directed at

embryo or IVF research; rather, both sections are exclusively centered

in a conventional understanding of aborted fetal tissue and the issues

arising from fetal tissue research; and 2) biological embryology, IVF,

and ES cell research typically include only “live” embryos that are

maintained in a living state for research purposes until they are either

implanted, disaggregated for living unicellular components, or terminated upon the experiment’s completion. A “dead human embryo”

would, by definition, comprise a multicellular tissue mass in which

all cellular functions associated with life activity had previously

ceased (clinical cell death), and would be more in the nature of a

stored pathology specimen. The draft guidelines of the NIH Ad Hoc

Working Group of the Advisory Committee to the Director support

this interpretation (NIH Ad Hoc Working Group 1999, 5).

50 Some private sector biotechnology companies have voluntarily

undertaken to self-regulate their research activities using IVF

embryos through the use of advisory boards and ethical protocols

(Geron Ethics Advisory Board 1998).

51 Public Law No. 105-277, 112 Stat. 2681 (1998).

52 45 CFR § 46.201(a).
42

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

53 45 CFR § 46.204(d), nullified by section 121(c) of the NIH

Revitalization Act of 1993, Public Law 103-43, June 10, 1993; 

see 59 Fed. Reg. 28276 (June 1, 1994).

54 DHHS has considered human embryo research only under the

category of IVF research, as defined in Subpart B (“any fertilization

of human ova which occurs outside the body of a female, either

through admixture of donor human sperm and ova or by any other

means,” 45 CFR § 46.203(g)) and hence it had been subject to the

requirement of EAB review prior to funding.

55 The 1993 Act deleted the requirement that IVF research be

reviewed by an EAB before it could be funded, but it did not remove

the remaining subsections of 45 CFR § 46.204, which prescribe the

basic structure and functions of the “one or more Ethical Advisory

Boards” that “shall be established by the Secretary” to provide advice

as needed on individual applications or “general policies, guidelines,

and procedures” covered by Subpart B, including the setting of

“class of applications or proposals which: (1) must be submitted 

to the Board, or (2) need not be submitted to the Board” 45 CFR 

§ 46.204 (a)-(c).

56 59 Fed. Reg. 28874, 28875 (June 3, 1994) (notice of meeting);

(NIH 1994, vol. 1, ix).

57 “[It] would not be wise to prohibit altogether the fertilization

and study of oocytes for research purposes....[H]owever, the embryo

merits respect as a developing form of human life and should be

used in research only for the most serious and compelling 

reasons....The Panel believes that the use of oocytes fertilized

expressly for research should be allowed only under two conditions.

The first condition is when the research by its very nature cannot

otherwise be validly conducted. The second condition...is when a

compelling case can be made that this is necessary for the validity 

of a study that is potentially of outstanding scientific and therapeutic

value” (NIH 1994, vol. 1, xi–xii).

58 “The Director of the National Institutes of Health has received a

recommendation regarding federal funding of research on human

embryos. The subject raises profound ethical and moral questions

as well as issues concerning the appropriate allocation of federal

funds. I appreciate the work of the committees that have considered this complex issue and I understand that advances in in vitro

fertilization research and other areas could derive from such work.

However, I do not believe that federal funds should be used to

support the creation of human embryos for research purposes, and

I have directed that NIH not allocate any resources for such

research. In order to ensure that advice on complex bioethical

issues that affect our society can continue to be developed, we are

planning to move forward with the establishment of a National

Bioethics Advisory Commission over the next year” (Office of the

White House Press Secretary, Statement by the President,

December 2, 1994). Although technically superseded in its effect

by the congressional appropriations rider governing DHHS, the

Directive remains effective throughout other Executive agencies.

This has not been formally inscribed as an Executive Order.

59 Public Law No. 104-99, Title I, § 128, 110 Stat. 26, 34 (1996).

The rider defines “human embryo” as “any organism, not protected

as a human subject under 45 CFR 46 as of the date of the enactment of this Act, that is derived by fertilization, parthenogenesis,

cloning, or any other means from one or more human gametes or

human diploid cells.” NIH has described the effect of the ban as

prohibiting “in vitro fertilization of a human egg for research 

purposes where there is no direct therapeutic intent...as well

as...research with embryos resulting from clinical treatment and

research on parthenogenesis.” The rider has been attached to the

subsequent DHHS appropriations, through the current Fiscal Year.

See Public Law No. 104-208, Div. A, § 101(e), Title V, § 512, 110

Stat. 3009, 3009-270 (1996); Public Law No. 105-78, Title V, 

§ 513, 111 Stat. 1467, 1517 (1997); Public Law No. 105-277, 

112 Stat. 2461 (1998).

60 Memorandum from Harriet Rabb to Harold Varmus, 

January 15, 1999. 

61 “NIH funds (including equipment, facilities, and supplies purchased on currently funded grants) should not be used to conduct

research using human pluripotent stem cells derived from human

fetal tissue or human embryos until further notice....While the NIH

proposes to support research utilizing these human pluripotent

stem cells, it will not do so until public consultation has occurred,

guidelines are issued, and an oversight committee has ensured that

each project is in accord with these guidelines. Research on human

stem cells derived from sources other than human embryos or fetal

tissue will not be subject to these guidelines and oversight: this

research will continue to be funded under existing policies and

procedures” (NIH 1999). The NIH Director’s caution has not

avoided public controversy, however (Members of the House of

Representatives 1999; Lanza, Arrow, Axelrod, et al. 1999).

62 “Opening Statement of Co-Chair Ezra C. Davidson, Jr., M.D.,”

Meeting of the NIH Ad Hoc Working Group of the Advisory

Committee to the Director, April 8, 1999 (NIH Ad Hoc Working

Group 1999). 

63 Letter from Gary B. Ellis, Director of the Office for Protection

from Research Risks, to Eric M. Meslin, Executive Director of the

National Bioethics Advisory Commission (NBAC), June 3, 1999.

64 45 CFR § 46.102(f).

65 In addition to their other duties, IRBs reviewing research subject to Subpart B must “1) Determine that all aspects of the activity

meet the requirements of this subpart; 2) Determine that adequate

consideration has been given to the manner in which potential

subjects will be selected, and adequate provision has been made by

the applicant or offeror for monitoring the actual informed consent

process (e.g., through such mechanisms, when appropriate, as participation by the Institutional Review Board or subject advocates

in: i) Overseeing the actual process by which individual consents

required by this subpart are secured either by approving induction

of each individual into the activity or verifying, perhaps through

sampling, that approved procedures for induction of individuals

into the activity are being followed, and ii) monitoring the progress

of the activity and intervening as necessary through such steps as
43

National Bioethics Advisory Commission

visits to the activity site and continuing evaluation to determine 

if any unanticipated risks have arisen); 3) Carry out such other

responsibilities as may be assigned by the Secretary” (45 CFR 

§ 46.205(a) (1997)). See also 45 CFR § 46.205(c) (1997)

(“Applicants or offerors seeking support for activities covered by

this subpart must provide for the designation of an Institutional

Review Board, subject to approval by the Secretary, where no such

Board has been established under Subpart A of this part.”).

66 See 45 CFR §§ 46.201-210, Subpart B, “Additional DHHS

Protections for Pregnant Women, Human Fetuses, and Newborns

Involved as Subjects in Research, and Pertaining to Human In Vitro

Fertilization,” Fed. Reg. 27794–27804 (May 20, 1998).

67 “In those states...embryo stem cell research is not banned,” but

see D.C. Code § 6-2601 (1998) prohibiting sale of any part of

human body (even cells), a restriction that may extend to human

embryos (Andrews 1999).

68 N.H. Rev. Stat. Ann. § 168-B:15 (limiting the maintenance of 

ex utero pre-implantation embryo in a noncryopreserved state to

under 15 days and prohibiting the transfer of research embryo to

the uterine cavity).

69 Louisiana broadly prohibits research involving IVF embryos. 

La. Rev. Stat. Ann. §§ 9:121–122 (West 1991). Eight other states

restrict embryo research indirectly, banning all research on “live”

embryos or fetuses. Fla. Stat. Ann. § 390.0111(6); Me. Rev. Stat.

Ann. tit. 22, § 1593 (West 1992); Mass. Ann. Laws ch. 112, 

§ 12j(a)(I) (Law. Co-op. 1996); Mich. Comp. Laws Ann. 

§§ 333.2685, 333.2686, 333.2692 (West 1992); Minn. Stat. Ann.

§ 145.422 Subd. 1,2 (West 1989); N.D. Cent. Code §§ 14-02.2-

01, 14-02.2-02 (1991); 18 Pa. Cons. Stat. Ann. § 3216(a) (Supp.

1995); R.I. Gen. Laws § 11-54-1(a)-(c) (1994) (Andrews 1999).

70 Me. Rev. Stat. Ann. tit. 22 § 1593; Mass. Ann. Laws ch. 112 

§ 12(j)(A)(Iv); Mich. Comp. Laws § 333.2609; N.D. Cent. Code 

§ 14-02.2-02(4); and R.I. Gen. Laws § 11-54-1(f).

71 Fla. Stat. Ann. § 873.05; Georgia Code Ann. § 16-12-160 (A)

(Except for Health Services Education); Ill. Stat. Ann. Ch 1101

/2

Para. 308.1; La. Rev. Stat. Ann. § 9:122; Minn. Stat. Ann. § 145.422(3)

(Live); 18 Pa. Cons. Stat. Ann. § 3216(b)(3) (forbids payment for

the procurement of fetal tissue or organs); Texas Penal Code 

§ 48.02; Utah Code Ann. § 76-7-311. But see Feiler (1998):

“Although some state laws prohibit the sale of fertilized embryos,

they do nothing to prevent the sale of gametes (sperm and eggs),

which can easily be converted into research embryos through

deliberate fertilization. Payment for sperm and eggs is widespread

among American infertility clinics” [citations omitted] (2455).

72 nn. 66; 75; 76; 80. Tenn. Code Ann. § 39-15-208 (199_) and

Utah Code Ann. § 76-7-311 (199_) prohibit sale of an “unborn

child”; D.C. Code § 6-2601 (199_) and Va. Code § 32.1-289.1

(199_) prohibit sale of all or a portion of the “human body” (D.C.)

or a “natural body part” (Va.); two state statutes prohibit sale of

specified organs (not including embryos), but permit state health

officials to expand the list under prescribed conditions. N.Y. Public

Health Law § 4307 (199_); W. Va. Code § 68.50.610(2) (199_)

(Andrews 1999). 

73 At least one state “prohibits the sale of living [embryos] or nonrenewable organs but does allow ‘the buying and selling of a cell

culture line or lines taken from a non-living human [embryo],’”

ibid., citing Minn. Stat. Ann. § 145.422(3) (Andrews 1999, citing

Minn. Stat. Ann. § 145.422(3)).

74 Office of the White House Press Secretary, “Memorandum for

the Heads of Executive Departments and Agencies,” March 4,

1997.

75 Executive Office of the President of the United States, 1998,

Statement of Administration Policy [on] S.1601 (Human Cloning

Prohibition Act) (Washington, DC: Executive Office of the

President).

References

Adams, A.M. 1988. “Background Leading to Meeting of the

Human Fetal Tissue Transplantation Research Panel Consultants.”

Report of the Human Fetal Tissue Transplantation Research Panel. 

Vol. 2, A3–A5. Bethesda, MD: National Institutes of Health (NIH).

Areen, J.C. 1988. “Statement on Legal Regulation of Fetal Tissue

Transplantation for the Human Fetal Tissue Transplantation

Research Panel.” Report of the Human Fetal Tissue Transplantation

Research Panel. Vol. 2, D21–D26. Bethesda, MD: NIH.

Bell, N.M.C. 1994. “Regulating Transfer and Use of Fetal Tissue in

Transplantation Procedures: The Ethical Dimensions.” American

Journal of Law and Medicine 20:277–294.

Canadian Royal Commission on New Reproductive Technologies.

1993. Proceed with Care: Final Report of the Royal Commission on

New Reproductive Technologies. 2 vols. Ottawa: Minister of

Government Services.

Clapp, M. 1988. “State Prohibition of Fetal Experimentation 

and the Fundamental Right of Privacy.” Columbia Law Review

88:1073–1097.

Coleman, J. 1996. “Playing God or Playing Scientist: A

Constitutional Analysis of State Laws Banning Embryological

Procedures.” Pacific Law Journal 27:1331–1399.

Department of Health, Education, and Welfare (DHEW). Ethics

Advisory Board (EAB). 1979. Report and Conclusions: HEW Support

of Research Involving Human In Vitro Fertilization and Embryo

Transfer. Washington, DC: U.S. Government Printing Office.

Driscoll, Jr., E. 1985. “Nobel Recipient John Enders, 88; Virus

Work Led to Polio Vaccine.” Obituary. Boston Globe, 10 September, 85.

Duguay, K.F. 1992. “Fetal Tissue Transplantation: Ethical and Legal

Considerations.” CIRCLES: Buffalo Women’s Journal of Law and Social

Policy 1:36. 

Duke, R.C. 1988. “Statement of the Population Crisis Committee.”

In Report of the Human Fetal Tissue Transplantation Research Panel.

Vol. 2. D112–D121. Bethesda, MD: NIH. 
44

Chapter 3: The Legal Framework for Federal Support of Research to Obtain and Use Human Stem Cells

Feiler, C.L. 1998. “Human Embryo Experimentation: Regulation

and Relative Rights.” Fordham Law Review 66:2435–2469.

General Accounting Office (GAO). 1997. Report to the Chairmen

and Ranking Minority Members, Committee on Labor and Human

Resources, U.S. Senate, and Committee on Commerce, House of

Representatives: National Institutes of Health-Funded Research:

Therapeutic Human Fetal Tissue Transplantation Projects Meet Federal

Requirements. Washington, DC: U.S. Government Printing Office.

Gelfand, G., and T.R. Levin. 1993. “Fetal Tissue Research: Legal

Regulation of Human Fetal Tissue Transplantation.” Washington and

Lee Law Review 50:647–694.

Geron Ethics Advisory Board. Geron Corporation. 1998. 

A Statement on Human Embryonic Stem Cells. 

Goddard, J.E. 1996. “The National Institutes of Health

Revitalization Act of 1993 Washed Away Many Legal Problems

with Fetal Tissue Transplantation Research But a Stain Remains.”

Southern Methodist University Law Review 49:375–399.

Lanza, R.P., K.J. Arrow, J. Axelrod, et al. 1999. “Science over

Politics.” Science 284:1849–1850.

Members of the House of Representatives. 1999. Statement of the

Members of the House of Representatives to the Working Group of the

Advisory Committee to the Director of the National Institutes of Health.

April 8.

National Commission for the Protection of Human Subjects of

Biomedical and Behavioral Research. 1975. Research on the Fetus:

Report and Recommendations. Washington, DC: U.S. Government

Printing Office.

NIH. 1987. “Human Fetal Tissue Research Supported by the

National Institutes of Health.” Summary Highlights of FY 1987.

Bethesda, MD: NIH. 

———. 1999. “National Institutes of Health Position on Human

Pluripotent Stem Cell Research.” Bethesda, MD: NIH. April 19,

www.nih.gov/grants/policy/stemcells.htm.

NIH. Ad Hoc Working Group of the Advisory Committee to the

Director. 1999. “Draft Guidelines for Research Involving

Pluripotent Stem Cell Research.” Bethesda, MD: NIH.

NIH. Human Embryo Research Panel. 1994. Report of the Human

Embryo Research Panel. 2 vols. Bethesda, MD: NIH.

NIH. Office of the Director (OD). 1999. “Fact Sheet on Stem Cell

Research.” Bethesda, MD: NIH, www.nih.gov/news/pr/apr99/od21.htm. 

Office for Protection from Research Risks (OPRR). 1994. Human

Subjects Protections: Fetal Tissue Transplantation—Ban on Research

Replaced by New Statutory Requirements. 29 April. 

Robertson, J.A. 1990. “Reproductive Technology and Reproductive

Rights. In the Beginning: The Legal Status of Early Embryos.”

Virginia Law Review 76:437–517.

———. 1993. “Abortion to Obtain Fetal Tissue for Transplant.”

Suffolk University Law Review 27:1359–1389.

Ryan, K.J. 1991. “Tissue Transplantation from Aborted Fetuses,

Organ Transplantation from Anencephalic Infants and Keeping

Brain-Dead Pregnant Women Alive Until Fetal Viability.” Southern

California Law Review 65:683–696.

Silva-Ruiz, P.F. 1998. “Section II: The Protection of Persons in

Medical Research and Cloning of Human Beings.” American Journal

of Comparative Law 46:151–163.

Windom, R.E. 1988. “Memorandum to James B. Wyngaarden,

March 22, 1988.” Report of the Human Fetal Tissue Transplantation

Research Panel. Vol. 2, A3. Bethesda, MD: NIH.

Zion, C. 1996. “The Legal and Ethical Issues of Fetal Tissue

Research and Transplantation.” Oregon Law Review 75:1281–1296.
Ethical Issues Relating to the 

Sources of Human Embryonic Stem 

or Embryonic Germ Cells

Research involving human embryonic stem (ES) cells

and embryonic germ (EG) cells raises several

important ethical issues, principally related to the current

sources and/or methods of deriving these cells. If, for

example, ES and EG cells could be derived from sources

other than human embryos or cadaveric fetal material,

fewer ethical concerns would be involved in determining

a policy for their use for scientific research or clinical

therapies. At present, however, the only methods available to isolate and culture human ES and EG cells involve

the use of human embryos or cadaveric fetal tissue.

Therefore, careful consideration of the ethical issues

involved in the use of these sources is an unavoidable

component of the advancement of this type of research.

This chapter first considers the ethical issues arising

from research involving the derivation and/or use of ES

or EG cells from three potential sources: cadaveric fetal

tissue, embryos resulting from and remaining after infertility treatments, and embryos created solely for research

purposes either by in vitro fertilization (IVF) or somatic

cell nuclear transfer (SCNT) techniques. The chapter

then reviews separately the specific arguments for and

against federal funding of this research. Finally, the chapter discusses relevant ethical issues in federal oversight

and review of research involving the derivation and/or

use of ES or EG cells.1

Research with EG Cells Derived from

Cadaveric Fetal Tissue

Many of the ethical questions regarding research

involving the use of cadaveric fetal tissue were analyzed

in depth by the 1988 National Institutes of Health (NIH)

Human Fetal Tissue Transplantation Research Panel.

What is new in the present context is that, in the near

term at least, the materials derived from this tissue would

not be transplanted; rather, gonadal tissue (both male

and female) would be used as a source for human EG

cells. Initially, these cell lines would be used in basic

research to determine their nature, to understand their

relationship to human development, and to identify differentiation factors that enable such cells to develop into

particular tissue types. Later, such cell lines also might be

used for the development of transplantation for particular tissue types. The value of cadaveric fetal tissue already

has been demonstrated; a broad variety of research materials and reagents derived from cadaveric fetal tissue currently are used in federally funded research.2

The ethical acceptability of deriving EG cells from the

tissue of aborted fetuses is, for some, closely connected to

the ethical acceptability of abortion. Those who believe

that elective abortions are morally acceptable are less

likely to identify insurmountable ethical barriers to

research that involves the derivation and use of EG cells

derived from cadaveric fetal tissue. This group might

agree that it is necessary to restrict such research by

requiring that the decision to donate fetal tissue be separate from the decision to terminate the pregnancy. The

purpose of such a requirement would be to protect the

pregnant woman against coercion and exploitation rather

than to protect the fetus. In addition, even those who

find it acceptable to use cadaveric fetal tissue in research

might hold that certain uses of such tissue—for example,

uses that treat it as nothing more than any other bodily

tissue—should be ruled out as disrespectful.

45

Ethical Issues in 

Human Stem Cell Research

Chapter Four 4
Chapter 4: Ethical Issues in Human Stem Cell Research

46

Those who view elective abortions as morally unjustified often—but not always—oppose the research use of

tissue derived from aborted fetuses. They usually have no

moral difficulty with the use of tissue from spontaneously

aborted fetuses or—if they recognize exceptions to the

moral prohibition on abortion—from fetuses in cases

that they believe are morally justifiable abortions (e.g., to

save the pregnant woman’s life). However, in general they

do not believe that it is possible to derive and use tissue

from what they believe are unjustifiably aborted fetuses

without inevitable and unacceptable association with

those abortions. This association, they believe, usually

taints the actions of all those involved in using these

materials or in financing research protocols that rely on

such tissue. Nevertheless, some opponents of elective

abortions believe that it is still possible to support such

research as long as effective safeguards are in place to separate abortion decisions from the procurement and use 

of fetal tissue in research. For them, when appropriate

safeguards are in place, using cadaveric fetal tissue from

elective abortions for research is relevantly similar to

using nonfetal cadavers donated for scientific and 

medical purposes.

Association with Abortion

Opponents of the research use of fetal materials

obtained from elective abortions dispute the claim that it

is possible to separate the moral issues surrounding the

abortion from those involved in obtaining and using fetal

material. They argue that those who obtain and use fetal

material from elective abortion inevitably become associated, in ethically unacceptable ways, with the abortions

that are the source of the material.3 They identify two

major types of unacceptable association or cooperation

with abortion: 1) causal responsibility for abortions and

2) symbolic association with abortions.

1. Causal Responsibility

Some believe that those who provide cadaveric fetal tissue in research are indirectly, if not directly, responsible

for the choice of some women to have an abortion. Direct

causal responsibility exists where, in this case, someone’s

actions directly lead a pregnant woman to have an

abortion—for example, the researcher offers financial

compensation for cadaveric fetal tissue and this compensation leads the pregnant woman to have an abortion

she would not otherwise have had. In part because of

concerns about direct causal responsibility, the Human

Fetal Tissue Transplantation Research Panel (1988) recommended the following safeguards to separate the

pregnant woman’s decision to abort from her decision to

donate fetal tissue:

■ The consent of women for abortions must be

obtained prior to requesting or obtaining consent for

the donation of fetal tissue.

■ Those who seek a woman’s consent to donate should

not discuss fetal tissue donation prior to her decision to abort, unless she specifically requests such

information. 

■ Women should not be paid for providing fetal tissue.

■ A separation must be maintained between abortion

clinic personnel and those involved in using fetal

tissue.

■ There should be a prohibition against any alteration

of the timing of or procedures used in an abortion

solely for the purpose of obtaining tissue. 

■ Donors of cadaveric fetal tissue should not be allowed

to designate a specific recipient of transplanted tissue.

As noted in Chapter 3, several of these safeguards

were later adopted in federal legislation regarding the use

of aborted fetal tissue in transplantation research, and

they appear to be sufficient to avoid direct causal responsibility for abortions in human EG research as well as in

transplantation research.

Those involved in research uses of EG cells derived

from fetal tissue could be indirectly responsible for abortions if the perceived potential benefits of the research

contributed to an increase in the number of abortions.

Opponents of fetal tissue research argue that it is unrealistic to suppose that a woman’s decision to abort can be

kept separate from considerations of donating fetal tissue, as many women facing the abortion decision are

likely to have gained knowledge about fetal tissue

research through the media or other sources. The knowledge that having an elective abortion might have benefits

for future patients through the donation of fetal tissue for

research may tip the balance in favor of going through

with an abortion for some women who are ambivalent

about it. Some argue that the benefits achieved through

the routine use of fetal tissue will further legitimize abortion and result in more permissive societal attitudes and

policies concerning elective abortion.
47

National Bioethics Advisory Commission

It is impossible to eliminate the possibility completely,

however slight it may be, that knowledge of the promise

of research on EG cells derived from fetal tissue will play

a role in some elective abortion decisions, even if only

rarely. However, it is not clear how much moral weight

ultimately attaches to this possibility. One might be justified in some instances in asserting that if it were not for

the research use of fetal tissue following an abortion, a

woman might not have chosen to terminate her pregnancy.

But one could assign this kind of causal responsibility to a number of factors that figure into abortion decisions without making ascriptions of indirect causal

responsibility, or what is sometimes called moral complicity. For example, a woman might choose to have an

abortion principally because she does not want to slow

the advancement of her education and career. She might

not have had an abortion in the absence of expectations

that encourage women to develop their careers. Yet, we

would not think it appropriate to charge those who promote such expectations and/or policies as complicit in

her abortion. In both this case and that of research, the

opportunity to choose abortion is a consequence of a

legitimate social policy. The burden on those seeking to

end such policies is to show that the risks of harm—both

the probability and the magnitude of harm—resulting

from the policies outweigh the expected benefits

(Childress 1991). This criterion minimally requires evidence of a high probability of a large number of elective

abortions that would not have occurred in the absence of

those policies. There is, however, no such evidence at

present. If compelling evidence did emerge that elective

abortions did, or probably would, increase as a result of

the research use of cadaveric fetal tissue, this would

require a re-examination of the balance of benefits and

harms as well as the safeguards that had been put into

place to eliminate the potential for direct causal responsibility and reduce the likelihood of indirect causal

responsibility for abortions.

2. Symbolic Association

People can become inappropriately associated with what

they believe are wrongful acts for which they are not

causally responsible. Particularly problematic for many is

an association that appears to symbolize approval of the

wrongdoing. For example, James Burtchaell maintains

that those involved in research on fetal tissue enter a

symbolic alliance with the practice of abortion in producing or deriving benefits from it (1988).

A common response is that persons can benefit from

what they might consider immoral acts without tacitly

approving of those acts. For example, transplant surgeons and transplant recipients may benefit (the latter

more directly than the former) from donated organs from

victims of murder or drunken driving but nevertheless

condemn those wrongful acts (Robertson 1988; Vawter et

al. 1991). A researcher who uses cadaveric fetal material

in studies to answer important research questions or to

study its potential therapeutic effects or the patient who

receives the donated tissue need not sanction the act of

abortion any more than the transplant surgeon who uses

the organs of a murder victim approves of the homicidal act.

Some opponents of fetal tissue research maintain that

it implicates those involved in a kind of wrongdoing that

cannot be attributed to the transplant surgeon in the

example above. Unlike drunken driving and murder,

abortion is an institutionalized practice in which certain

categories of human life (the members of which are considered by some to have the same moral status as human

adults) are allowed to be killed. In this respect, some

opponents of abortion go so far as to suggest that fetal tissue research is more analogous to research that benefits

from experiments conducted by Nazi doctors during

World War II (Bopp 1994).

But whatever one thinks of comparisons between the

victims of Nazi crimes and aborted fetuses—and many

are outraged by these comparisons—it is possible to concede the comparisons without concluding that human

stem cell research involving cadaveric fetal tissue is

morally problematic. Of course, some believe that those

who use data derived from Nazi experiments are morally

complicit with those crimes. For example, William

Seidelman writes: 

By giving value to (Nazi) research we are, by implication, supporting Himmler’s philosophy that the

subjects’ lives were ‘useless.’ This is to argue that, by

accepting data derived from their misery we are,

post mortem, deriving utility from otherwise ‘useless’ life. Science could thus stand accused of giving

greater value to knowledge than to human life itself

(1988, 232). 
48

Chapter 4: Ethical Issues in Human Stem Cell Research

But one need not adopt this stance. Instead, one can

reasonably believe that a scientist’s actions must be

understood and judged not by their consequences or

uses but rather by several other factors, including the

scientist’s intentions, the social practices of which his

or her actions are a part, and the social context in

which those practices are embedded. As philosopher

Benjamin Freedman wrote:

A moral universe such as our own must, I think, rely

on the authors of their own actions to be primarily

responsible for attaching symbolic significance to

those actions...[I]n using the Nazi data, physicians

and scientists are acting pursuant to their own moral

commitment to aid patients and to advance science in

the interest of humankind. The use of data is predicated upon that duty, and it is in seeking to fulfill that

duty that the symbolic significance of the action must

be found (1992, 151).

It is likewise reasonable to maintain that the symbolic

significance of support for research using EG cells

derived from aborted fetal tissue lies in the commitment

and desire to gain knowledge, promote health, and save

lives. This research is allied with a worthy cause, and any

taint that might attach from the source of the cells

appears to be outweighed by the potential good that the

research may yield.

Consent and Donation 

In previous debates about the use of fetal tissue in

research, questions have been raised about who has the

moral authority to donate the material. Some assert that,

from an ethical standpoint, a woman who chooses abortion forfeits her rights to determine the disposition of the

dead fetus. Burtchaell, for instance, argues that “the decision to abort, made by the mother, is an act of such violent abandonment of the maternal trusteeship that no

further exercise of such responsibility is admissible”

(1988, 9). By contrast, John Robertson argues that this

position mistakenly assumes that the persons disposing

of cadaveric remains act only as the guardians or proxies

of the deceased. Instead, “a more accurate account of

their role is to guard their own feelings and interests in

assuring that the remains of kin are treated respectfully”

(1988, 6).

In our view, obtaining consent to donate fetal tissue is

an ethical prerequisite for using such material to derive

EG cells, even though the woman or couple are not

research subjects per se, and even though the cadaveric

fetus is not a human subject. This view is consistent with

the conclusion of the Human Fetal Tissue Transplantation Research Panel, which held that “[e]xpress donation by the pregnant woman after the abortion decision

is the most appropriate mode of transfer of fetal tissues

because it is the most congruent with our society’s traditions, laws, policies, and practices, including the

Uniform Anatomical Gift Act and current Federal

research regulations” (1988, 6). According to this panel,

a woman’s choice of a legal abortion does not disqualify

her legally and should not disqualify her morally from

serving “as the primary decisionmaker about the disposition of fetal remains, including the donation of fetal tissue for research.” She “has a special connection with the

fetus and she has a legitimate interest in its disposition

and use.” In addition, her decision to donate fetal tissue

would not violate the dead fetus’s interests. The panel

concluded that “in the final analysis, any mode of

transfer other than maternal donation appears to raise

more serious ethical problems” (6). Fetal tissue should

not be used without the woman’s consent. Not only should

her consent be necessary, it should also be sufficient to

donate the tissue, except where the father’s objection 

is known.

We concur with the Human Fetal Tissue Transplantation Research Panel that a woman undergoing an elective abortion should be authorized to donate fetal tissue,

unless the father is known to object. We further agree

with the panel and with subsequent federal legislation

that it is important to establish safeguards to separate the

pregnant woman’s decision to abort from the decision to

donate cadaveric fetal tissue. The guidelines already in

place for fetal tissue transplantation research generally

are appropriate and appear to be sufficient if they also

apply to research involving human EG cells.

As already noted, some opponents of elective abortion can support fetal tissue research as long as there are

safeguards to avoid direct causal responsibility and to

reduce the likelihood of indirect causal responsibility.

Many who view elective abortion as morally problematic,

even if not always morally unjustified, also may endorse
49

National Bioethics Advisory Commission

these safeguards as a way to avoid certain forms of association with morally problematic actions and at the same

time as a way to prevent the exploitation and coercion of

pregnant women. Even those who do not find elective

abortions morally problematic may accept these safeguards in order to protect pregnant women from

exploitation and coercion as well as to sustain social practices that reflect important social and cultural values and

to respect the moral concerns of opponents of elective

abortion. We believe, therefore, that there can be wide

agreement on appropriate safeguards for the process of

donating cadaveric fetal tissue.

At a minimum, these safeguards should separate the

decision to have an abortion from the decision to donate

by ensuring, as much as possible, that the former occurs

before the latter by not providing before the abortion

decision is made information about the possibility of

using fetal materials in research and by prohibiting the

provision of financial compensation for the fetal tissue to

the woman (or to the couple) having the abortion. If

these and other requirements that already have been

adopted in regulations governing federally funded

human fetal tissue transplantation research do not clearly extend to research to generate EG cells from cadaveric

fetal tissue, the regulations should be modified to do so.

Research with ES Cells Derived from Embryos

Remaining After Infertility Treatments

Ethical issues arising from research involving the use

of human embryos have generated a sustained public

policy discussion and a valuable body of literature that

spans at least 20 years. Some of these issues were considered in depth by the Department of Health, Education

and Welfare (DHEW) Ethics Advisory Board (EAB) in

1978 and in 1979 (DHEW Ethics Advisory Board 1979).

The ethical debate was continued here and abroad by

other national advisory bodies, including the British

Warnock Committee (Committee of Inquiry 1984) and

the Canadian Royal Commission on New Reproductive

Technologies (1993). In 1994, the NIH Human Embryo

Research Panel considered multiple types of present and

future human embryo research and discussed both ethical and public policy issues (NIH 1994). In contrast, for

example, SCNT has been seriously debated in the United

States and elsewhere only for about two years, and the

research use of SCNT has been debated for an even

shorter period.

One source of embryos for ES cells is those remaining

after infertility treatments. Couples who provide such

embryos have decided that they no longer need them to

achieve their reproductive goals. If the couple prefers to

discontinue storing the remaining embryos and does not

wish to donate them to other couples, the only alternatives are to direct that the embryos be discarded (that is,

to destroy them through the thawing process) or to

donate them for research. When only these latter two

alternatives remain, the situation is somewhat similar to

that in which a woman is deciding whether to donate

fetal tissue for research following elective abortion and

the situation in which families are deciding whether to

donate the organs or tissues of a loved one who has

recently died. However, whether this similarity is decisive

depends upon one’s perception of the moral status of

embryos. Derivation of ES cells involves destroying the

embryos, whereas abortion precedes the donation of the

fetal tissue and death precedes the donation of whole

organs for transplantation.

The Moral Status of Embryos

To say that an entity has “moral status” is to say something both about how one should act towards that thing

or person and about whether that thing or person can

expect certain treatment from others. The debate about

the moral status of embryos traditionally has revolved

around the question of whether the embryo has the same

moral status as children and adult humans do—with a

right to life that may not be sacrificed by others for the

benefit of society. At one end of the spectrum of attitudes

is the view that the embryo is a mere cluster of cells that

has no more moral status than any other collection of

human cells. From this perspective, one might conclude

that there are few, if any, ethical limitations on the

research uses of embryos.

At the other end of the spectrum is the view that

embryos should be considered in the same moral category

as children or adults. According to this view, research

involving the destruction of embryos is absolutely prohibited. Edmund D. Pellegrino, a professor of bioethics 

at Georgetown University, described this perspective

in testimony given before the Commission:
50

Chapter 4: Ethical Issues in Human Stem Cell Research

The Roman Catholic perspective...rejects the idea

that full moral status is conferred by degrees or at

some arbitrary point in development. Such arbitrariness is liable to definition more in accord with experimental need than ontological or biological reality.4

In contrast, scholars representing other religious traditions testified that moral status varies according to the

stage of development.5 For example, Margaret Farley, a

professor of Christian ethics at Yale University, pointed

out that

There are clear disagreements among Catholics—

whether moral theologians, church leaders, ordinary

members of the Catholic community—on particular

issues of fetal and embryo research....A growing

number of Catholic moral theologians, for example,

do not consider the human embryo in its earliest

stages...to constitute an individualized human entity.6

Other scholars from Protestant, Jewish, and Islamic 

traditions noted that major strands of those traditions

support a view of fetal development that does not assign

full moral status to the early embryo.7 For example,

Jewish scholars testified that the issue of the moral status

of extra-corporeal embryos is not central to an assessment of the ethical acceptability of research involving 

ES cells. Rabbi Elliot Dorff noted that

Genetic materials outside the uterus have no legal status in Jewish law, for they are not even a part of a

human being until implanted in a woman’s womb

and even then, during the first 40 days of gestation,

their status is ‘as if they were water.’ As a result, frozen

embryos may be discarded or used for reasonable

purposes, and so may stem cells be procured from

them.8

As a result, for some Jewish thinkers, the derivation and

use of ES cells from embryos remaining after infertility

treatments may be less problematic than the use of

aborted fetal tissue, at least following morally unjustified

abortions.

On this issue, the Commission adopted what some

have described as an intermediate position, one with

which many likely would agree: that the embryo merits

respect as a form of human life, but not the same level of

respect accorded persons. We recognize that, on such a

morally contested issue, there will be strong differences

of opinion. Moreover, it is unlikely that, by sheer force of

argument, those with particularly strong beliefs on either

side will be persuaded to change their opinions (Murray

1996). However, there is, in our judgment, considerable

value in describing some of these positions, not only to

reveal some of the difficulties of resolving the issue, but

to seek an appropriate set of recommendations that can

reflect the many values we share as well as the moral

views of those with diverse ethical commitments.

A standard approach taken by those who deny that

embryos are persons with the same moral status as children and adults is to identify one or more psychological

or cognitive capacities that are considered essential to

personhood (and a concomitant right to life) but that

embryos lack. Most commonly cited are consciousness,

self-consciousness, and the ability to reason (Feinberg

1986; Tooley 1983; Warren 1973). The problem with

such accounts is that they appear to be either under- or

over-inclusive, depending on which capacities are

invoked. For example, if one requires self-consciousness

or the ability to reason as an essential condition for

personhood, most very young infants will not be able

to satisfy this condition. On the other hand, if sentience

is regarded as the touchstone of the right to life, then

nonhuman animals also possess this right. 

Those who deny that embryos have the same moral

status as persons might maintain that the embryo is simply too nascent a form of human life to merit the kind of

respect accorded more developed humans. However,

some would argue that, in the absence of an event that

decisively (i.e., to everyone’s satisfaction) identifies the

first stage of human development—a stage at which

destroying human life is morally wrong—it is not permissible to destroy embryos.

The fundamental argument of those who oppose the

destruction of human embryos is that these embryos are

human beings and, as such, have a right to life. The very

humanness of the embryo is thus thought to confer the

moral status of a person. The problem is that, for some,

the premise that all human lives at any stage of their

development are persons in the moral sense is not selfevident. Indeed, some believe that the premise conflates

two categories of human beings: namely, beings that

belong to the species homo sapiens, and beings that
51

National Bioethics Advisory Commission

belong to a particular moral community (Warren 1973).

According to this view, the fact that an individual is a

member of the species homo sapiens is not sufficient to

confer upon it membership in the moral community of

persons. Although it is not clear that those who advance

this view are able to establish the point at which, if ever,

embryos first acquire the moral status of persons, those

who oppose the destruction of embryos likewise fail to

establish, in a convincing manner, why society should

ascribe the status of persons to human embryos.

It is not surprising that these different views on the

moral status of the embryo appear difficult to resolve,

given their relationship to the issues surrounding the

abortion debate, a debate the philosopher Alastair

MacIntyre describes as interminable: “I do not mean by

this just that such debates go on and on and on—

although they do—but also that they can apparently find

no terminus. There seems to be no rational way of securing moral agreement in our culture” (1984, 6). This

difficulty has led most concerned observers to search for

a position that respects the moral integrity of different

perspectives, but to the extent possible, focuses public

policy on ethical values that may be broadly shared.

The Importance of Shared Views

Once again, we are aware that the issue of the moral

status of the embryo has occupied the thoughtful attention of previous bodies deliberating about fetal tissue and

embryo research.9 Further, as already noted, we do not

presume to be in a position to settle this debate, but

instead have aimed to develop public policy recommendations regarding research involving the derivation and

use of ES cells that are formulated in terms that people

who hold differing views on the status of the embryo can

accept. As Thomas Nagel argues, “In a democracy, the

aim of procedures of decision should be to secure results

that can be acknowledged as legitimate by as wide a portion of the citizenry as possible” (1995, 212). In this vein,

Amy Gutmann and Dennis Thompson argue that the

construction of public policy on morally controversial

matters should involve a “search for significant points of

convergence between one’s own understandings and

those of citizens whose positions, taken in their more

comprehensive forms, one must reject” (1996, 85).

R. Alta Charo suggests an approach for informing policy in this area that seeks to accommodate the interests of

individuals who hold conflicting views on the status of

the embryo. Charo argues that the issue of moral status

can be avoided altogether by addressing the proper limits of embryo research in terms of political philosophy

rather than moral philosophy:

The political analysis entails a change in focus, away

from the embryo and the research and toward an

ethical balance between the interests of those who

oppose destroying embryos in research and those

who stand to benefit from the research findings.

Thus, the deeper the degree of offense to opponents

and the weaker the opportunity for resorting to the

political system to impose their vision, the more

compelling the benefits must be to justify the funding

(1995, 20).

In Charo’s view, once one recognizes that the substantive

conflict among fundamental values surrounding embryo

research cannot be resolved in a manner that will satisfy

all sides, the most promising approach is to seek to

balance all the relevant considerations in determining

whether to proceed with the research. Thus, although it

is clear that embryo research would offend some people

deeply, she would argue that the potential health benefits for this and future generations outweigh the pain

experienced by opponents of the research.

It is, however, questionable whether Charo’s analysis

successfully avoids the issue of moral status. It might be

argued, for example, that placing the lives of embryos in

this kind of utilitarian calculus will seem appropriate

only to those who presuppose that embryos do not have

the status of persons. Those who believe—or who genuinely allow for the possibility—that embryos have the

status of persons will regard such consequentialist

grounds for destroying embryos as extremely problematic. 

In our view, an appropriate approach to public policy

in this arena is to develop policies that demonstrate

respect for all reasonable alternative points of view and

that focus, when possible, on the shared fundamental

values that these divergent opinions, in their own ways,

seek to affirm. This particular perspective was recommended by Patricia King in her testimony before the

Commission and elsewhere (1997).10 As long as the
52

Chapter 4: Ethical Issues in Human Stem Cell Research

disagreement is cast strictly as one between those who

think the embryo is a person with a right to life and those

who think it has little or no moral status, the quest for

convergence will be an elusive one. But there are grounds

for supposing that this may be a misleading depiction of

the conflict. Indeed, there may be a sufficiently broad

consensus regarding the respect to be accorded to

embryos to justify, under certain conditions, not only the

research use of stem cells but also the use of embryos

remaining after infertility treatments to generate ES cells.

The abortion debate offers an illustration of the complex middle ground that might be found in ethically and

politically contentious areas of public policy. Philosopher

Ronald Dworkin maintains that, despite their rhetoric,

many who oppose abortion do not actually believe that

the fetus is a person with a right to life. This is revealed,

he claims, through a consideration of the exceptions

that they often permit to their proposed prohibitions

on abortion.

For example, some hold that abortion is morally permissible when a pregnancy is the result of rape or incest.

Yet, as Dworkin comments, “[i]t would be contradictory

to insist that a fetus has a right to live that is strong

enough to justify prohibiting abortion even when childbirth would ruin a mother’s or a family’s life, but that

ceases to exist when the pregnancy is the result of a

sexual crime of which the fetus is, of course, wholly

innocent” (1994, 32).

The importance of reflecting on the meaning of such

exceptions in the context of the research uses of embryos

is that they suggest that even in an area of great moral

controversy it may be possible to identify some common

ground. If it is possible to find common ground in the

case of elective abortions, we might be able to identify

when it would be permissible in the case of destroying

embryos. For example, conservatives allow such exceptions implicitly hold with liberals that very early forms of

human life may sometimes be sacrificed to promote the

interests of other humans.11 Although liberals and conservatives disagree about the range of ends for which

embryonic or fetal life may ethically be sacrificed, they

may be able to reach some consensus. Conservatives who

accept that destroying a fetus is permissible when necessary to save a pregnant woman or spare a rape victim

additional trauma might agree with liberals that it also is

permissible to destroy embryos when it is necessary to

save lives or prevent extreme suffering. We recognize, of

course, that these cases are different, as the existence of

the fetus may directly conflict with the pregnant

woman’s interests, while a particular ex utero embryo

does not threaten anyone’s interests. But this distinction

obscures the fact that these two cases share an implicit

attribution of greater value to the interests of children

and adults.

We believe that the following would seem to be a

reasonable statement of the kind of agreement that could

be possible on this issue:

Research that involves the destruction of embryos

remaining after infertility treatments is permissible

when there is good reason to believe that this destruction is necessary to develop cures for life-threatening

or severely debilitating diseases and when appropriate

protections and oversight are in place in order to

prevent abuse.

Given the great promise of ES cell research for saving

lives and alleviating suffering, such a statement would

appear to be sufficient to permit, at least in certain cases,

not only the use of ES cells in research, but also the use

of certain embryos to generate ES cells. Some might

object, however, that the benefits of the research are too

uncertain to justify a comparison with the conditions

under which one might make an exception to permit

abortion. But the lower probability of benefits from

research uses of embryos is balanced by a much higher

ratio of potential lives saved relative to embryonic lives

lost and by two other characteristics of the embryos used

to derive ES cells: first, that they are at a much earlier

stage of development than is usually true of aborted

fetuses, and second, that they are about to be discarded

after infertility treatment and thus have no prospect for

survival even if they are not used in deriving ES cells. In

our view, the potential benefits of the research outweigh

the harms to embryos that are destroyed in the research

process.

Another objection is that the availability of alternative

means of obtaining (and sources of) stem cells makes it

unnecessary to use embryos to obtain ES cells for

research. Richard Doerflinger of the National Conference
53

National Bioethics Advisory Commission

of Catholic Bishops testified before the Commission that

“it is now clearer than ever that new research involving

adult stem cells...offers the promise that embryonic stem

cells may simply be irrelevant to future medical

progress.”12 In our judgment, the derivation of stem cells

from embryos remaining following infertility treatments

is justifiable only if no less morally problematic alternatives are available for advancing the research. But as we

have noted, ES cells from embryos appear to be different

in scientifically important ways from AS cells and also

appear to offer greater promise of therapeutic breakthroughs. The claim that there are alternatives to using

stem cells derived from embryos is not, at the present

time, supported scientifically. We recognize, however,

that this is a matter that must be revisited continually as

science advances.

Nevertheless, if research is to proceed with the

derivation and use of ES cells from embryos that remain

following infertility treatments, we must consider what

kinds of conditions and constraints should apply to this

work. Many of these conditions, discussed below, also are

reflected in our recommendations that are provided in

the next chapter.

First, ideally, those who have the authority to decide

about the disposition of the remaining embryos should

make the decision about whether to donate them to

another couple, to continue to store them, or to destroy

them before they are asked about donating them for

research. This will reduce the likelihood that a desire to

benefit research will lead to a choice to destroy the

embryos. If the decision to destroy the embryos precedes

the decision to donate them for research purposes, then

the research use of such embryos affects only how, not

whether, the destruction occurs. Obviously, this separation may not be possible, particularly because the couple

may be given several options simultaneously, either at the

outset of treatment for infertility or after its completion.

Indeed, some infertility programs provide patients with

multiple consent forms at the outset of treatment, forms

that include options to donate to research, discard, or

transfer any embryos that remain. But even then, it may

be appropriate to view the options as consisting of donation of the embryos to another couple, their continued

storage, or their destruction, with destruction of the

embryos taking one of two forms—discarding them

through thawing or through the process of research. If

embryo destruction is permissible, then it certainly

should be permissible to destroy them in a way that

would generate stem cells for bona fide research.

Second, the couple’s or the individual’s decision to

donate any remaining embryos for research should be a

voluntary one, free from coercion and undue pressure.

Third, donors of embryos for research should not be

allowed to designate or restrict the recipients of derivative tissues or cell lines for research or therapy. Fourth,

even though it is legal to sell sperm and ova, it should

remain illegal to sell embryos; the demonstration of

respect for embryos requires this prohibition. Fifth, only

the minimum number of embryos that are needed to

derive sufficient stem cells for important research should

be used in this way.

Sixth, it is important to develop and widely disseminate additional professional standards of practice in

reproductive medicine that will reduce the likelihood

that infertility clinics will increase the numbers of

embryos remaining after infertility treatments in order to

increase the supply for possible research purposes. These

standards could address issues such as the production of

embryos, the number of embryos implanted and allowed

to develop to term, and the care and handling of gametes

and embryos.

Seventh, any research use of embryos or embryonic

cell lines imported from outside of the country must satisfy all the regulations for the use of such materials when

they are produced in the United States. Eighth, if possible, institutions, researchers, and potential recipients of

therapies should be informed in some way about the

source of the stem cells—perhaps by tagging the cells—

so that all concerned can avoid using any cells that are

believed to have been derived unethically. This last condition is intended to enable institutions, researchers, and

patients to make their own conscientious choices about

the acceptability of using stem cells that have been

derived from ethically controversial sources.
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Chapter 4: Ethical Issues in Human Stem Cell Research

Ethical Distinctions and Relationships Between the

Derivation and Use of ES Cells Derived from

Embryos Remaining After Infertility Treatments

There is significant debate regarding whether the use

of cultures of ES cells should be regarded or treated

differently from the derivation of such cells, given that the

derivation arises from the destruction of an intact

embryo. For purposes of this report, three questions will

help frame this issue: First, are derivation and use ethically distinct? Second, is the use of ES cells, their derivation, or both ethically justifiable? Third, should use,

derivation, or both be eligible for public funding? Here

we discuss our views on the first two questions. Later in

this chapter, we discuss the third question in more detail.

Even though many individuals would want to avoid

the use of ES cells because of their source, the processes

of derivation and use are sufficiently different to warrant

being regarded as morally distinct from one another. The

NIH Human Embryo Research Panel reached this conclusion as well (1994). Moreover, we heard testimony

that would support this distinction.13 However, there is

vigorous debate regarding whether this distinction, even

if morally relevant, is morally decisive or determinative

for judgments about particular actions and public

policies.

As previously discussed, most moral concerns about

the derivation of ES cells from embryos that remain after

infertility treatments focus on the fact that derivation

involves destruction. If embryos could be destroyed 

by allowing them to thaw—the standard approach to discarding them—and researchers could then derive ES

cells, the moral issues would be parallel to those that

arise in the derivation of germ cells from aborted fetuses.

Destruction and derivation could be separated in principle as well as through various practical measures.

However, in practice, destruction and derivation cannot

be separated; therefore, this option is not available. The

question, then, is whether the use of ES cells derived in 

a process that destroys the embryos can be morally 

separated from that of derivation.

There are several possible responses. One position

holds that such use is morally unacceptable because it

necessarily involves association with the wrongful act of

embryo destruction. Another position is that the problem

of associating the use of the cells and the destruction of

the embryo disappears if the destruction of the embryo is

not viewed as problematic, as some traditions hold.

There is no association with wrongdoing if the initial act

is not on balance wrong. A third position holds that even

if embryo destruction is viewed as morally wrong, there

still may be ways to separate at least some uses from derivation. John Robertson suggests that there may be some

circumstances in which researchers using ES cells would

not be considered complicit with the destruction of

embryos. He indicates, for example, that there would be

no meaningful association where an investigator’s

“research plans or actions had no effect on whether the

original immoral derivation occurred” (1999, 113). 

Some commentators hold that it would be ethically

justifiable, though regrettable, to use existing cell lines

that were derived through unethical embryo destruction.

A version of this position was suggested by Father

Demetrios Demopulos, who explained his views from the

perspective of Eastern Orthodoxy in testimony before the

Commission:

...I cannot condone any procedure that threatens 

viability, dignity, and sanctity of that life. In my view

the establishment of embryonic stem cell lines...was

done at the cost of human lives. Even though not yet

a human person, an embryo should not be used for

or sacrificed in experimentation, no matter how noble

the goal may seem.14

Yet, in response to a Commissioner’s inquiry about

whether it might still be permissible to use existing ES

cell lines, Demopulos stated:

In my opinion, yes, since the lines exist and they have

some benefit. I wish they had not been derived in the

way that they were but since they are there....I do not

think it would be a good thing to not take advantage

of [their availability].15 

In our reflections on both the distinction and relationship between derivation and use, especially for purposes of determining ethically acceptable public policy,

we were influenced by testimony that stressed how

important it is for public policy to be clear and to be justified in terms that are widely understood. Individuals

representing widely differing views about the moral
55

National Bioethics Advisory Commission

status of the embryo and the moral justifiability of

embryo destruction offered similar testimony. For example, Gilbert Meilaender called for the Commission to

avoid misleading and even deceptive language in its

statement and justification of public policies, whatever

those policies turned out to be, on the grounds that misleading language would be a disservice to public discourse.16 While affirming a different view regarding the

moral status of embryos and embryo destruction, Dena

Davis made a similar point by stressing that public policy and its rationale should pass the “straight-face test,” a

test failed, in her judgment, by an interpretation of federal law that permits federal funding of research using

stem cells while denying federal funding of research that

involves deriving the cells themselves. According to

Davis, “it is disrespectful to suggest that those who

believe that human embryos are persons look the other

way when embryos are destroyed to obtain stem cells as

long as public funding only kicks in once the stem cells

are derived.” Moreover, she argued that it is “more

respectful, both of individuals opposed to the research

and the public discourse generally, to be explicit about

what is going on here and to acknowledge the ethical if

not legal linkage between embryo destruction and the

deriving of stem cells.”17

The legal opinion rendered by the Department of

Health and Human Services distinguishes the current

legality of providing federal funds for the downstream

use of ES cells from the legality of providing funds for the

derivation of these cells. Indeed, as noted in Chapter 3,

our own independent legal analysis reached a similar

conclusion.18 However, because our report focuses on the

ethical issues involved in human ES and EG cell research,

we find that there is no inconsistency between accepting

this legal analysis and, at the same time, concluding that

research involving both the derivation and use of these

cells can under certain circumstances be justified ethically

and that federal funds should be provided for both. We

examine the ethical arguments for and against funding

both derivation and use after we consider another possible source of stem cells–embryos that are created solely

for research.

Research with ES Cells Derived from Embryos

Created Solely for Research

Ever since the NIH Human Embryo Research Panel

recommended that under certain conditions embryos

could be created solely for research purposes (1994),

there has been an ongoing discussion about the ethical

and scientific merit of such a practice. Following is a discussion of this issue as it relates to two sources of ES cells

derived from embryos that are created solely for research

purposes.

Embryos Created Using IVF Procedures

There are two significant arguments in favor of creating human embryos using IVF technologies solely for

stem cell research: The first is that there may be an inadequate supply of embryos remaining after infertility treatments. The second is that important research that could

be of great medical benefit cannot be undertaken except

with well-defined embryos that are created specifically

for research and/or medical purposes. However, recommending federal funding for research using or deriving

ES cells from embryos expressly created for research purposes presents two ethical problems. First, unlike in the

case of embryos that remain following infertility treatments, there does not appear to be sufficient societal

agreement on the moral acceptability of this practice at

this time. Second, it is unclear whether an adequate supply of ES cells from embryos is available to meet scientific

need or whether specialized cells are needed. We do not,

at this time, support the federal sponsorship of research

involving the creation of embryos solely for research

purposes. However, we recognize that, in the future, scientific evidence and public support for this type of stem

cell research may be sufficient in order to proceed.

Therefore, to promote ongoing dialogue on this topic, we

offer the following discussion.19

The “Discarded-Created” Distinction: On the

Importance of Intentions 

Various parties have discussed whether there is a

moral difference between conducting research on

embryos created with the intention of using them for

reproduction and conducting research on embryos created with the intention of using them for research (Annas,
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Chapter 4: Ethical Issues in Human Stem Cell Research

Caplan, and Elias 1996; Capron 1999; Davis 1995;

Edwards 1990). Embryos created with the intention of

using them for reproduction become available for

research only when it is known that they are no longer

intended to be used for infertility treatments; only then

are they considered discarded, and only then do they

become potentially available for research. The second

group of embryos—research embryos—are those that are

created without the intention that they will be used for

procreative purposes. Rather, they are developed solely

for research purposes or to generate research and medical

materials such as stem cells or other cell lines, clones,

DNA sequences, or proteins.

For some observers, it is difficult to defend an ethical

distinction between what one can do with an embryo

that has been created solely for research purposes and

what one can do with an embryo remaining from infertility treatments (Davis 1995). For others, conducting

research on embryos that were originally created for

reproduction but which were then discarded is far easier

to justify than is research conducted on embryos that

were originally created for research (Harris 1998).

An ethical intuition that seems to motivate the “discarded-created” distinction is that the act of creating an

embryo for reproduction is respectful in a way that is

commensurate with the moral status of embryos, while

the act of creating an embryo for research is not. Embryos

that are discarded following the completion of IVF treatments were presumably created by individuals who had

the primary intention of implanting them for reproductive purposes. These individuals did not consider the

destruction of these embryos until it was determined that

they were no longer needed. By contrast, research

embryos are created for use in research and, in the case

of stem cell research, their destruction in the process of

research. Hence, one motivation that encourages serious

consideration of the “discarded-created” distinction is a

concern about instrumentalization—treating the embryo

as a mere object—a practice that may increasingly lead us

to think of embryos generally as means to our ends rather

than as ends in themselves. 

The Use of SCNT to Produce ES Cells

Somatic cell nuclear transfer of a diploid nucleus into

an oocyte also has been suggested as a method to generate

embryos from which ES cells could be derived. If successful, tissues derived from such cells could be useful in

avoiding graft rejection if the donor nucleus were taken

from the eventual transplant recipient. Although fertilization of an egg with sperm in vitro clearly results in a

human zygote that will divide to become an embryo and

has the potential to develop into a human if implanted, it

is less clear whether the embryo created through SCNT

has that potential. Nevertheless, the fact that this technique can produce living animals such as sheep and cows

strongly suggests that it is likely that the cell that results

from insertion of an adult nucleus into an oocyte is a

zygote and can become an embryo. 

Some have argued, however, that it is not clear that a

zygote produced in this manner is similar to an embryo

created by fertilization, because there are significant differences in the ability to generate different animals using

these techniques, and we do not understand the potential of the human cell in this context. Because it is unclear

whether SCNT works equally well in all species, we do

not yet know whether this technique works in humans.

Currently, therefore, we are uncertain whether cells created using SCNT have the full potential to become

human. Because of previous work showing the potential

of SCNT to create an animal in some situations, many

would argue that similar concerns about the creation of

embryos for research purposes apply to embryos created

by SCNT. Thus, because of moral concerns outlined

above regarding the creation of life only for research purposes, this category of research is disturbing to some. In

the future, however, research may define conditions

under which SCNT can be carried out while culturing the

cells in such a manner that the resulting cell is directed 

to immediately differentiate into a specific tissue, precluding further development into an embryo. Perhaps in

the future, then, it will be possible to use SCNT without

the creation of an embryo.

One major distinction between IVF and SCNT

embryos is that while creation of embryos by IVF would

only generate more embryos, generation of embryos by

SCNT would generate a specific kind of cell that might be

useful in treating disease by allowing autologous transplant of a specific tissue type. Thus, in balancing the

moral concern over the creation of an embryo and the

value to society of the SCNT embryo, the potential therapeutic uses of the resulting ES cells from SCNT embryos

must be evaluated carefully. At the present time, insufficient scientific evidence exists to evaluate this potential;

however, within the next several years, such information

should become more abundant. We recognize that if our
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National Bioethics Advisory Commission

recommendations are accepted, the most likely way that

this information will accumulate is through research

carried out in the private sector.

We are aware, however, that if the use of SCNT to create embryos for research purposes were deemed to be

both scientifically and medically necessary, other ethical

issues still would need to be addressed. For example, we

would need to revisit the current prohibition on designating a recipient of fetal or embryonic tissue, in light of

the likelihood that this would be an important motivator

for producing such embryos.

The Arguments Relating to Federal

Funding of Research Involving the

Derivation and/or Use of ES and EG Cells

This chapter has described several issues that arise when

considering the ethical acceptability of stem cell research,

depending on the source of the ES or EG cells. These

issues are not unique to the source of funding, however,

as they could apply equally to stem cell research conducted in either the private or public sector. Because our

main interest is in providing advice and guidance regarding the federal government’s role in funding research that

involves the derivation and/or use of ES and EG cells, we

now turn to an examination of arguments both for and

against such funding. 

Arguments Against Federal Funding of Certain

Types of Human Stem Cell Research

In our deliberations, we considered three major arguments against federal funding of certain types of stem cell

research: its association with abortion and embryo

destruction, objections by some citizens to having federal

funds used for research they consider to be objectionable,

and the possibility that federal funds could be used for

research using AS cells rather than ES or EG cells. Each

argument is briefly considered below.

Association with Abortion and Embryo Destruction

As discussed earlier, research in this area is controversial in part because of the belief, held by some, that

there is a direct or indirect association with abortion. For

those who hold this belief, federal funding of research

that derives EG cells from cadaveric fetal tissue after elective abortion also would involve moral association with

the act of abortion.20 Similarly, federal funding for the use

of embryos remaining after infertility treatments to obtain

ES cells would involve the federal government in deliberately destroying biologically human entities.

Federal Funding for ES and/or EG Cell Research

Violates the Deeply Held Moral Beliefs of Some

Citizens

By funding research of this kind, opponents argue

that the federal government is violating the beliefs of

some citizens, including the belief that they should not

be required to subsidize a practice they consider to be

morally objectionable. If it is possible to achieve essentially the same legitimate public goals with a policy that

does not offend some citizens’ sincere moral sensibilities,

it would be better to do so. Sometimes, the federal government decides not to support an activity because it

would be offensive to many people and because the benefits lost from this support are minimal, either because

the activity is of only marginal value or because other

sponsors will ensure that a worthwhile activity receives

the support it needs. Not infrequently, however, activities

that produce valuable results and that are legitimate

objects of government funding receive such support

despite the objections raised by some taxpayers.

Providing such support does not violate democratic principles or infringe on the rights of dissent of those in the

minority. Of course, the existence of such strongly held

dissenting views makes more necessary a careful assessment of the arguments in favor of government support of

the activity.

Funding Alternative Sources of Stem Cell Research

Is Morally Preferable

The Commission has considered the argument that a

targeted and vigorous program that aims to develop alternative sources of human stem cells could discover ways

to achieve the same therapeutic goals with the use of

ethically less controversial means. As noted above and in

Chapter 2, research on AS cells is still developing and

should be encouraged, but on scientific grounds there is

good reason to believe that ES cells will provide a more

reliable source of cells that can differentiate into a variety

of tissues. It also should be noted that the harvesting of

AS cells is technically difficult and risky to human beings.

For some types of adult cells, such as bone marrow cells,
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Chapter 4: Ethical Issues in Human Stem Cell Research

a certain amount of pain and discomfort is involved. For

other types of stem cells, such as neuronal cells from the

brain, there are significant risks to the donor from the

brain biopsy procedure.

Although these objections to federal funding are

important, they are not decisive. Regarding the objection

based on association with wrongdoing, this report joins

others in supporting various safeguards in the context of

abortion in order to avoid any direct causal responsibility,

to reduce the likelihood of any indirect causal responsibility, and to blunt symbolic association. Our report also

proposes safeguards to prevent inappropriate and unnecessary use of embryos that remain following IVF.

Regarding the second objection—avoiding offense to

those who are morally opposed to using embryos for this

purpose—we believe that public policy should avoid

such offense in cases where the costs are not great, and

we propose ways in which to reduce such offense.

However, in this area of moral controversy, we believe

that the arguments in favor of federal funding outweigh

the offense that federal funding would create for some.

Finally, we agree that alternative sources of stem cells

should be sought when possible and that federal funds

should be allocated to finding those sources. However, at

the same time, we believe that on balance the ethical

and scientific arguments support pursuing important

research with EG cells obtained from cadaveric fetal

tissue, with ES cells from embryos remaining after infertility treatments, and with other promising alternative

sources. We now turn to additional arguments that lead

us to support federal funding for certain types of ES and

EG cell research.

Arguments in Favor of Federal Funding for

Certain Types of Stem Cell Research

One of the principal ethical justifications for public

sponsorship of research with human ES and EG cells is

the same as for all biomedical and behavioral research in

this country: Such research has the potential to produce

health benefits for individuals suffering from disease.

Many of the potential benefits of research using human

ES or EG cells are discussed in Chapter 2.

The appeal to the potential benefits of stem cell

research provides strong moral grounds for federal support of such research, but these potential benefits are not

necessarily sufficient to justify this support. The pursuit

of social benefit is always subject to moral constraint.

Concerns for justice and respect for the rights of individuals can trump the morally laudable pursuit of potential

benefits. Such concerns also may justify additional

constraints on public funding of research. 

The Enhancement of Scientific Progress Through

Federal Support of the Derivation of ES Cells

Although ES cell lines already exist from studies conducted in the past year, relying upon these lines or upon

the few other cell lines that might be derived by private

companies for basic research on human stem cells could

severely limit progress in this area of science. As discussed in Chapter 2, the potential to realize the possible

medical benefits of ES cells depends on additional

research into the nature and properties of ES cells. There

are three main scientific reasons why it is beneficial for a

broader segment of the scientific community to conduct

research that involves both the derivation and use of

ES cells.

First, there is great scientific value in understanding

the process of ES cell derivation. Basic scientists who are

interested in fundamental cellular processes are likely to

make important discoveries about the nature of ES cells

as they derive them in the laboratory. Moreover, by funding both derivation and use, under appropriate circumstances, federally funded researchers will be able to take

advantage of the knowledge that arises from a detailed

understanding of the source of the materials and the

methods of derivation. Experience with animal studies

indicates that research that involves both the derivation

and use of particular cell lines has the greatest probability

of generating promising new results.

Second, the properties of ES cells differ depending

upon the conditions that were used to derive them.

Moreover, the conditions for derivation of human ES

cells that will differentiate into all tissue types are not yet

fully understood by researchers. It is clear that the conditions used for mouse ES cells do not translate directly

when using cells from other mammals. There is a significant amount of basic research that needs to be done

regarding the process of ES cell derivation before the benefits from cell-based therapies can be realized.

Third, ES cells in culture are not stable indefinitely. As

the cells are grown in culture, irreversible changes occur

in their genetic makeup. Thus, especially in the first few
59

National Bioethics Advisory Commission

years of human ES cell research, it is important to repeatedly derive ES cells to be sure that the properties of the

cells that are being studied have not changed.

The Benefits of Encouraging Both Public and

Private Support for ES and EG Cell Research

We anticipate that in order for stem cell research to

proceed most effectively, it will require an environment in

which both public and private funding will be available.

Indeed, in his testimony before the Commission, David

Blumenthal suggested that “since prohibition of federal

funding of stem cell research will result in reliance on private companies to support almost all the investigation

utilizing stem cells, the differences between industrially

funded and publicly funded university investigation are

pertinent to your [deliberations].”21 Increasingly, research

is being supported and conducted by industry. Support

for biomedical research and development from private

sector pharmaceutical and biotechnology companies

now outstrips the funding from all federal sources for this

research, and it is likely that the field will continue to

develop even if no federal funding is forthcoming. The

drug industry recently estimated that $24 billion will be

spent on drug research and development in 1999, up

from $2 billion in 1980 (PhRMA 1998). In light of this,

some might question whether federal funding for the

derivation and use of ES cells from embryos remaining

from infertility treatments is necessary for future progress

in this field.

We believe that a combination of federal and private

sector funding is more likely to produce rapid progress in

this field than would private sector funding alone. An

entire cadre of researchers is likely to be drawn into this

field of research through the establishment of a federal

funding program. Perhaps an analogy with the field of

higher education is useful. It would be possible for all

college and university education in the United States to

be offered solely by privately funded colleges or universities. However, the combination of publicly and privately

funded schools allows the higher education system as a

whole to capitalize on the unique strengths of each type

of institution. Competing, yet often working together, the

two types of institutions may be able to achieve levels of

excellence that neither type could achieve by itself.

Synergy from a Combined Federal Effort for

Research Involving Use and Derivation

Federal funding provides the opportunity for collaboration and coordination among a much larger group of

researchers. Moreover, the availability of federal funding

would likely increase greatly the number of scientists carrying out ES and EG cell research and thus increase the

chance of important findings. Federal support for

research will encourage basic research on the biology of

stem cells, in addition to the product-oriented research

typically supported by biotechnology firms that are

focused on developing marketable products. However, in

the long run, advances in the basic biology of stem

cells—for example, increased understanding of the conditions and signals that lead stem cells to differentiate or

of the detailed mechanisms of differentiation—are essential for therapeutic advances. Such basic research will

require long-term efforts, which traditionally have been

supported by NIH.*

*Commissioner Capron makes the following observations: “As described in Chapter 3 and mentioned earlier in this chapter, NIH, relying on the opinion of the

General Counsel of DHHS, has concluded that the present rider to the Department’s appropriation allows the funding of research using but not deriving ES cells

from embryos because the latter would involve destroying embryos for research purposes. The alternative policy urged in this report would, in addition to its 

scientific benefits, also enable the federal government to play a stronger role in ensuring that ethically acceptable processes are used in deriving the ES cells that

federally supported scientists use in their research. Specifically, adopting a limited exception to the funding ban solely to allow support of ES cell line derivation

from embryos donated from fertility programs provides a stronger platform for the federal government to enforce the distinction between research using this

group of embryos and that which would use embryos created solely for research purposes.

Of course, even if NIH funds only ‘use’ research, it could still try to require that the ES cells used not be derived from embryos created for research purposes.

But its moral leverage is undermined by its own rationale: By insisting that federal funding of research using human ES cells does not implicate federal sponsors in

the process by which the ES cells have been derived, it limits its ability to mandate that one process rather than another be used. Plainly, federal law could restrict

federal support to activities that do not, for example, cause unlawful pollution; by extension, the limitation could extend to activities that do not purchase materials

that were produced in processes that pollute. In the present case, however, the appropriations rider bans federal support for research that creates or destroys

human embryos, which means that a federal agency cannot claim to be implementing federal policy were it to limit funding to research that uses only those 

ES cells that were derived from discarded embryos but not from embryos created for the purpose of deriving ES cells. Thus, NIH may be hard pressed to justify

differentiation based on the type of embryos from which ES cells are derived, thereby losing an opportunity to oversee the derivation process directly and to

enforce an important ethical distinction.

Adopting a limited exception to the embryo research ban solely for research to derive ES cells from embryos remaining from fertility programs would also

avoid relying on the theoretical line between derivation and use research that underlies the NIH policy. Such a line is difficult to defend in practical terms when

the question is not whether an activity is inherently licit or illicit but whether it ought to be paid for with federal research dollars. Any such line is merely

theoretical because the funding provided for research using ES cells would of course flow directly to researchers deriving those cells, perhaps even in an adjacent

laboratory. The only difference would be that the federal funds would not go directly as salary and laboratory expenses for the derivation process but indirectly in

the form of funds to purchase the ES cells (which funds would then pay salaries, laboratory expenses, and so forth).”
60

Chapter 4: Ethical Issues in Human Stem Cell Research

Requiring That Recipients Conduct Their Research

in Accordance with the Federal Regulations 

As with all federally sponsored research, conditions

attached to funding provide the federal government with

the authority to require compliance with relevant regulations, policies, and guidelines. Among these regulations

are those pertaining to human subjects research, tissue

donation and transplantation, oversight, and review. In

addition, federal funding agencies can stipulate that

recipients of federal funding for human stem cell research

must share both research results and research materials

(including cell lines) with other recipients of federal

funds or with all other researchers. Thus, federal funding

may lead to more widespread dissemination of findings

and sharing of materials, which ultimately may enhance

scientific discoveries.

In contrast, many privately funded studies require

that the scientists not distribute their findings until after

a review by the company and that materials can be

shared only after the institution receiving the materials

has signed a material transfer agreement. Some of these

agreements make it difficult for scientists to share or

secure the reagents necessary for their research, even if

they wish to do so. As the Institute of Medicine noted in

its report, Resource Sharing in Biomedical Research, “The

perception that scientific data and research materials

(e.g., animals, reagents, etc.) have potential commercial

value frequently causes universities to be even more

reluctant than individual scientists with respect to

sharing” (1996, 81). 

Sustaining U.S. Leadership in Science 

and Technology

In supporting federal funding for certain types of

stem cell research, we are not opposing research in the

private sector. On the contrary, we recognize the value for

the nation’s investment in science and technology for

research sponsored and conducted by both the public

and the private sectors and the quality of private sector

research. Indeed, stem cell research is receiving, and

probably will continue to receive, increasing support

from industry. There are, however, certain specific advantages that arise from the federal investment in science

that should be acknowledged. An observation made by

the Office of Technology Assessment, in its 1986 report,

Research Funding as an Investment, is relevant in this

context.

The goal of federally funded research is not profitability, but a means of achieving social objectives,

whether they are health, national security, or the

enhancement of knowledge and education. The

Federal research infrastructure is designed to provide

a stable environment for these goals, despite a changing political environment....In addition, Federal

research programs must be responsive to many more

groups than industrial research efforts, and this affects

the manner in which the research agenda is shaped.

(1986, 61)

Federal funding is probably required in order for the

United States to sustain a leadership position in this

increasingly important area of research. By funding

research, the federal government conveys the clear message that, under particular conditions and constraints,

certain types of human stem cell research can be morally

legitimate research that is worthy of public support.

Just Distribution of Potential Benefits from

Stem Cell Research 

Much of the testimony we heard indicated that the

just distribution of the benefits of stem cell research,

including both the knowledge gained and any potential

therapeutic benefits, should be taken into account in any

recommendation that would permit the federal government to support ES and EG cell research. For example,

there was widespread agreement among the religious

scholars who testified before us that in order for this

research to be morally acceptable, several “background

factors” must be in place, including equitable access to

the benefits of the research and appropriate prioritization

of this research relative to other social needs, both of

which involve procedural and substantive justice. (See

Appendix E.)

Issues of procedural and substantive justice are not

unique to stem cell research but rather arise in various

societal decisions about the use of funds for research,

medical care, and other goods. Although we can note

these issues here, we cannot resolve them. In addition,

federal funding of stem cell research does not guarantee
61

National Bioethics Advisory Commission

that greater numbers of the American public will have

access to the fruits of basic or applied research or that this

will occur more quickly than it would if federal funding

were not available. However, by recommending federal

funding for certain types of human stem cell research, we

acknowledge that there is a basis for an argument for

broader access to any therapies developed from that

research.

Ethical Issues in Adopting Federal

Oversight and Review Policies for 

ES and EG Cell Research

Concerns have been expressed regarding the likelihood

of accountability depending on whether ES and EG cell

research is sponsored and/or conducted by the public or

private sector. Arthur Caplan, a bioethicist at the

University of Pennsylvania, in testimony before the

Senate Subcommittee on Labor, Health and Human

Services, Education and Related Agencies, said that

...it is better to do things in this area that are accountable and public, than it is to ask them to become private and commercial. And if we continue the policies

we have, we’re not going to be able to bring the

nuanced supervision and oversight that this area of

stem cell research requires from us....That’s why we

need public funding, public accountability, to make

the right tradeoffs.22

One of the principal benefits of federal funding of

biomedical and behavioral research is that it is relatively

easy to put in place an effective system of public oversight and review. By oversight, we are referring to the

mechanism of monitoring categories of research or other

activities to determine compliance with policies, procedures, rules, guidelines, and regulations and to prevent

abuses. It is a policy strategy designed to provide the

appropriate checks and balances and ensure ethically

acceptable research protocols. The existing federal system of oversight has its origins both in the legislative and

executive branches of the federal government: Congress,

through its appropriations authority, may (and often

does) direct that certain research be undertaken or avoided.

Seen in this way, federal oversight can provide the public

with two assurances: first, that stem cell research will

receive national attention and scrutiny through the

appropriations process undertaken by Congress; and

second, that stem cell research would be conducted in

accordance with relevant federal regulations. These oversight components are necessary but not sufficient for providing the public with confidence that research,

especially research involving human subjects, is being

undertaken appropriately. There also are mechanisms

maintained by individual agencies such as the Food and

Drug Administration.

In contrast, review usually refers to the evaluation of

individual research protocols involving human subjects

to assess their scientific merit and ethical acceptability—

the activity usually carried out by Institutional Review

Boards. As noted above, however, some research involving human stem cells may not be considered research

involving human subjects, as defined by the Common

Rule. In our view, the considerable sensitivity and public

concern regarding stem cell research merits both national

and local approaches to oversight and review, the details

of which are described in the following chapter. We are

persuaded that federal oversight and review of some

types of stem cell research is required in order to make

federal funding available to support such research. The

types of questions about ES and EG cell research that we

consider important for such an oversight and review

body to ask are enumerated in Appendix F.

Summary

We were asked by the President to thoroughly review the

issues associated with stem cell research, “balancing all

ethical and medical considerations.” In this chapter, we

have endeavored to do just that. Specifically, we recognized that there are many different views on the ethical

appropriateness of this type of research and also on the

appropriateness of providing federal funding for such

research. We believe that the ethical arguments that support the use of federal funds for stem cell research using

cadaveric fetal tissue and for both deriving and using ES

cells from embryos remaining after infertility treatments

have considerable merit. However, such research should

be conducted only within the context of a framework of

national oversight and review. At the same time, we were
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Chapter 4: Ethical Issues in Human Stem Cell Research

not persuaded that we should recommend that federal

funds be available at this time for the creation of embryos

solely for research purposes. We arrived at these conclusions with full awareness of the strongly held views (from

both religious and secular ethical perspectives) on all

sides of the main issues regarding the morality of stem

cell research.

Notes

1 The arguments presented here were helpfully informed by two

papers prepared for the National Bioethics Advisory Commission

(NBAC) by Fletcher, J.C., 1999, “Deliberating Incrementally on

Human Pluripotential Stem Cell Research,” and Siegel, A.W., 1999,

“Locating Convergence: Ethics, Public Policy and Human Stem

Cell Research.” Both of these papers are available in Volume II of

this report.

2 Eiseman, E., 1999, “Quick Response: Use of Human Fetal Tissue

in Federally Funded Research.” This paper was prepared for NBAC

and is available in Volume II of this report.

3 Several terms have been used to refer to inappropriate connections between one agent’s actions and another agent’s wrongdoing.

We have mainly used the term association, but other terms include

cooperation, collaboration, and complicity. See, for example,

Childress (1990). For a discussion of cooperation and complicity

with evil in Roman Catholic moral theology, see Maguire (1986).

4 Pellegrino, E.D., Testimony before NBAC. May 7, 1999.

Washington, DC. Meeting transcript, 10.

5 For a summary of these positions, see Appendix E. 

6 Farley, M., Testimony before NBAC. May 7, 1999. Washington,

DC. Meeting transcript, 18.

7 Dorff, E., M. Tendler, L. Zoloth, A. Sachedina. Testimony before

NBAC. May 7, 1999. Washington, DC.

8 Dorff, E., Testimony before NBAC. May 7, 1999. Washington,

DC. Meeting transcript, 48. 

9 For a discussion of these issues see the paper prepared for NBAC

by Knowles, L.P., 1999, “International Perspectives on Human

Embryo and Fetal Tissue Research,” available in Volume II of this

report. 

10 King, P.A., Testimony before NBAC. January 19, 1999.

Washington, DC.

11 The terms liberal and conservative used here are used in the 

context intended by Dworkin (1994), Life’s Dominion.

12 Doerflinger, R., Written testimony before NBAC. April 16,

1999. Charlottesville, VA. Meeting transcript, 1.

13 Pellegrino, E.D., Testimony before NBAC. May 7, 1999.

Washington, DC. 

14 Demopulos, D., Testimony before NBAC. May 7, 1999.

Washington, DC. Meeting transcript, 89.

15 Ibid.

16 Meilaender, G., Testimony before NBAC. May 7, 1999,

Washington, DC.

17 Davis, D., Testimony before NBAC. May 7, 1999. Washington,

DC. Meeting transcript, 164. 

18 This opinion was provided by Flannery, E., 1999, in “Analysis

of Federal Laws Pertaining to Funding of Human Pluripotent Stem

Cell Research,” available in Volume II of this report. 

19 For a discussion of these issues see the paper prepared for

NBAC by Parens, E., 1999, “What Has the President Asked of

NBAC? On the Ethics and Politics of Embryonic Stem Cell

Research,” available in Volume II of this report.

20 It is important to note, however, that the abortion exceptions,

which serve as the basis for the type of shared views identified

above, are exceptions to the law banning federal funding for 

abortions (Title V, Labor, HHS, and Education Appropriations, 

112 Stat. 3681-385, Sec. 509 (a) (1)&(2)). Thus, federal funding

for research use of cadaveric fetal tissue, within appropriate limits,

might be viewed as consistent with current federal funding 

practices in the abortion context. 

21 Blumenthal, D., Written testimony before NBAC. February 2,

1999. Princeton, NJ. Meeting transcript, 1.

22 Caplan, A.L., Testimony before the Senate Appropriations

Subcommittee on Labor, Health, and Human Services, Education

and Related Agencies. December 2, 1998.

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Capron, A.M. 1999. “Good Intentions.” Hastings Center Report

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Childress, J.F. 1990. “Disassociation from Evil: The Case of Human

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———. 1991. “Ethics, Public Policy, and Human Fetal Tissue

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Introduction

I

n November 1998, President Clinton charged the

National Bioethics Advisory Commission with the

task of conducting a thorough review of the issues

associated with human stem cell research, balancing all

ethical and medical considerations. The President’s request

was made in response to three separate reports that

brought to the fore the exciting scientific and clinical

prospects of stem cell research while also raising a series

of ethical controversies regarding federal sponsorship of

scientific inquiry in this area. Such research raises ethical

issues because it involves the derivation of human embryonic

germ (EG) cells from aborted fetuses or the derivation of

human embryonic stem (ES) cells from early stage

embryos remaining after infertility treatments. A number

of these important ethical concerns previously have been

identified in public debate, both here and abroad. The

Commission reviewed these concerns in light of both the

medical and scientific promise in this significant new

field and the existing statutes and regulations that affect

research in this area. Our task, however, was neither to

engage in moral analysis for its own sake nor to address

all the regulatory issues that might be raised, but rather

to offer advice on how the balance of ethical, scientific,

and medical considerations should shape policies on

the use of federal funds to support research that involves

deriving or using human ES or EG cells.

Scientific and Medical Considerations 

The stem cell is a unique and essential cell type found in

animals. Many kinds of stem cells are found in the human

body, with some more differentiated, or committed, to a

particular function than others. In other words, when

stem cells divide, some of the progeny mature into cells

of a specific type (heart, muscle, blood, or brain cells),

while others remain stem cells, ready to repair some of

the everyday wear and tear undergone by our bodies.

These stem cells are capable of continually reproducing

themselves and serve to renew tissue throughout an individual’s life. For example, they continually regenerate the

lining of the gut, revitalize skin, and produce a whole

range of blood cells. Although the term stem cell commonly is used to refer to those cells within the adult

organism that renew tissue (e.g., hematopoietic stem

cells, a type of cell found in the blood), the most fundamental and extraordinary of the stem cells are found in

the early stage embryo. These ES cells, unlike the more

differentiated adult stem (AS) cells or other cell types,

retain the special ability to develop into nearly any cell

type. EG cells, which originate from the primordial reproductive cells of the developing fetus, have properties similar

to ES cells.

It is the potentially unique versatility of the ES and EG

cells derived, respectively, from the early stage embryo

and cadaveric fetal tissue that presents such unusual

scientific and therapeutic promise. Indeed, scientists have

long recognized the possibility of using such cells to generate more specialized cells or tissue, which could allow

the newly generated cells to be used to treat injuries or

diseases such as Alzheimer’s disease, Parkinson’s disease,

heart disease, and kidney failure. In addition, scientists

regard these cells as important—perhaps essential—in

understanding the earliest stages of human development

and in developing life-saving drugs and cell-replacement

therapies to treat disorders caused by early cell death or

65

Conclusions and

Recommendations

Chapter Five 5
66

Chapter 5: Conclusions and Recommendations

impairment. At the same time, the techniques for deriving

these cells have not been fully developed as standardized

and readily available research tools, and the development

of any therapeutic application remains some years away. 

Research also is under way to determine whether

human stem cells could be obtained from the differentiated

stem cells of fully developed organisms. Thus far, however, studies in animals indicate that this approach faces

substantial scientific and technical limitations; indeed,

the anatomic source of certain cells might preclude easy

or safe access in human beings. In addition, important

biological differences apparently exist between ES cells,

EG cells, and AS cells. Furthermore, differences among

species mean that for full scientific and clinical benefits to

be realized, some research will need to be conducted

with human ES and EG cells, even as the emphasis

remains on laboratory and animal research. In summary,

research using stem cells from animals or from human

adults is not a substitute for human ES and EG cell

research, and it is toward the latter that we direct our

ethical and policy analyses.

Ethical and Policy Considerations 

The longstanding controversy about the ethics of

research involving human embryos and cadaveric fetal

material arises from fundamental and sharply differing

moral views regarding elective abortion or the use of

embryos for research. Indeed, an earnest national and

international debate continues over the ethical, legal, and

medical issues that arise in this arena. This debate represents both a challenge and an opportunity: a challenge

because it concerns important and morally contested

questions regarding the beginning of life, and an opportunity because it provides another occasion for serious

public discussion about important ethical issues. We are

hopeful that this dialogue will foster public understanding about the relationships between the opportunities

that biomedical science offers to improve human welfare

and the limits set by important ethical obligations. 

Although we believe most would agree that human

embryos deserve respect as a form of human life, disagreements arise regarding both what form such respect

should take and what level of protection is required at

different stages of embryonic development. Therefore,

embryo research that is not therapeutic to the embryo is

bound to raise serious concerns for some about how to

resolve the tensions between two important ethical commitments: to cure disease and to protect human life. For

those who believe that from the moment of conception

the embryo has the moral status of a person, research (or

any other activity) that would destroy the embryo is

considered wrong and should be prohibited. For those

who believe otherwise, arriving at an ethically acceptable

policy in this arena involves a complex balancing of

many important ethical concerns. Although many of the

issues remain contested on moral grounds, they can exist

within a broad area of consensus upon which public policy

can, at least in part, be constructed. 

For most observers, the resolution of these ethical and

scientific issues depends to some degree upon the source

of the stem cells. The use of cadaveric fetal tissue to

derive EG cell lines—like other uses of tissues or organs

from dead bodies—is generally the most acceptable of

these sources, provided that the research complies with

the system of public safeguards and oversight already in

place for such scientific inquiry. With respect to embryos

and the ES cells from which they can be derived, some

draw an ethical distinction among three potential types

of embryos. One is referred to as the research embryo, an

embryo created through in vitro fertilization (IVF), with

gametes provided solely for research purposes. Many

people, including the President, have expressed the view

that the federal government should not fund research

that involves creating such embryos. The second type of

embryo is that which was created for treatment of infertility, but is now intended to be discarded because it is

unsuitable or no longer needed for such treatment. The

use of these embryos raises fewer ethical questions

because it does not alter their final disposition. Finally,

the recent demonstration of cloning techniques (somatic

cell nuclear transfer [SCNT]) in nonhuman animals suggests that the transfer of a human somatic cell nucleus

into an oocyte might create an embryo that could be used

as a source of ES cells. The creation of a human organism

using this technique raises questions similar to those

raised by the creation of research embryos through IVF,

and at this time federal funds may not be used for such
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National Bioethics Advisory Commission

research. In addition, if the enucleated oocyte that was to

be combined with a human somatic cell nucleus came

from a nonhuman animal, other issues would arise about

the nature of the embryo produced. Thus, each source of

material raises distinct ethical questions as well as

scientific, medical, and legal ones.

Conscientious individuals have reached different conclusions regarding both public policy and private actions

in the area of stem cell research. Their differing perspectives by their very nature cannot easily be bridged by any

single public policy. But the development of such policy

in a morally contested area is not a novel challenge for a

pluralistic democracy such as that which exists in the

United States. We are profoundly aware of the diverse

and strongly held views on the subject of this report and

has wrestled with the implications of these different

views at each of our meetings devoted to this topic. Our

aim throughout these deliberations has been to formulate

a set of recommendations that fully reflects widely shared

views and that, in our view, would serve the best interests

of society.

Most states place no legal restrictions on any of the

means of creating ES and EG cells that are described in

this report. In addition, current Food and Drug

Administration (FDA) regulations do not apply to this

type of early stage research. (See Appendix D.) Therefore,

because the public controversy surrounding such activities in the United States has revolved around whether it

is appropriate for the federal government to sponsor such

research, this report focuses on the question of whether

the scientific merit and the substantive clinical promise of

this research justify federal support, and, if so, with what

restrictions and safeguards.

Views about the status of embryos and fetuses vary

widely. Some believe that what matters is the potential for

a new human life that arises at the moment of conception,

while others identify the relevant concept as personhood,

which they say begins only at some postembryonic stage.

We heard from many members of the public, including

those who are eager for this area of research to move forward as rapidly as possible, as well as those who oppose

the research if it is built upon any activity that is connected to abortion or to the destruction of fertilized

human eggs. In addition, our deliberations have been

informed by testimony from scientists and physicians,

lawyers and other experts in governmental regulation,

philosophers, and Catholic, Protestant, Jewish, Islamic,

and Eastern Orthodox theologians. As a result of these

discussions, it has become clear that the question of

whether federal policy should sponsor human ES or EG

cell research is characterized by a tension between the

desire to realize the great therapeutic benefits that may be

derived from such work and the need to recognize that

the materials involved must be treated with respect. We

concluded that sufficient safeguards can be put in place

in order to prevent abuse and to ensure that any use of

embryos that remain after infertility treatments—like any

use of fetal remains following elective abortion—is based

upon and embodies the kind of respect for the embryos

that most Americans would expect and demand of any

activity that is carried out with the support of the federal

government. Beyond the regulatory effects of the rules

adopted to govern federal support for research in this

area—with which we hope private sponsors of research

involving ES and EG cells will comply voluntarily—the

states also can influence research in this field through

statutes and regulations on abortion, embryo research, and

the donation of human body parts, embryos, and gametes.

Conclusions and Recommendations

The conclusions and recommendations presented in this

chapter are grouped into several categories: 

■ the ethical acceptability of federal funding for

research that either derives or uses ES or EG cells,

■ the requirements for the donation of cadaveric fetal

tissue and embryos for research, 

■ restrictions on the sale of these materials and 

designation of those who may benefit from their use,

■ the need—and the means—for national oversight and

institutional review,

■ the need for local review of derivation protocols, 

■ the responsibilities of federal research agencies,

■ the issues that must be considered regarding the 

private sector, and 

■ the need for ongoing review and assessment. 
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Chapter 5: Conclusions and Recommendations

The Ethical Acceptability of Federal Funding of

ES Cell and EG Cell Research 

Despite the enormous scientific and clinical potential

offered by research use of ES or EG cells derived from

various sources, many find that certain sources are more

ethically problematic than others. Our recommendations

reflect respect for these diverse views, which varied even

among the Commissioners, regarding the ethical acceptability of the derivation and use of ES and EG cells from

various sources. 

As described in Chapter 2, human ES and EG cells

can be derived from the following sources:

■ human fetal tissue following elective abortion (EG cells),

■ human embryos that are created by IVF and that are

no longer needed by couples being treated for infertility (ES cells),

■ human embryos that are created by IVF with gametes

donated for the sole purpose of providing research

material (ES cells), and

■ potentially, human (or hybrid) embryos generated

asexually by SCNT or similar cloning techniques in

which the nucleus of an adult human cell is introduced into an enucleated human or animal ovum

(ES cells).

A principal ethical justification for public sponsorship

of research with human ES or EG cells is that this

research has the potential to produce health benefits for

those who are suffering from serious and often fatal

diseases. We recognize that it is possible that all the 

various sources of human ES or EG cells eventually could

be important to research and clinical application because

of, for example, their differing proliferation potential, 

differing availability and accessibility, and differing ability

to be manipulated, as well as possibly significant differences in their cell biology.

Although each source of stem cells poses its own

scientific, ethical, and legal challenges and opportunities,

much of the ethical analysis leading to public policy

recommendations depends upon the scientific and/or

clinical necessity of using a specific source of the cells.

In our judgment, the immediate scientific uses of ES or

EG cells can be satisfied by the derivation and use of

cell lines derived from fetal tissues (i.e., EG cells) and

from embryos (i.e., ES cells) remaining after infertility

treatments have ended. 

The potential use of matched tissue for autologous

cell-replacement therapy from ES cells may in the future

require the use of cell lines developed by SCNT techniques. In addition, embryos created through IVF

specifically as a source of ES cells might be essential for

creating banks of multiple cell lines representing a spectrum of alleles for the major histocompatibility complex.

This goal might require that ova and sperm of persons

with specific genotypes be selected to make embryos

from which to derive particular classes of ES cells.

Finally, although much promising research currently

is being conducted with stem cells obtained from adult

organisms, studies in animals suggest that this approach

will be scientifically and technically limited, and, in some

cases, the anatomic source of the cells might preclude

easy or safe access. Important research can and should 

go forward in this area, although important biological

differences exist between ES and AS cells, and the use of

AS cells should not be considered an alternative to ES

and EG cell research.

Much research into the generation of specific tissue

types from stem cells can be conducted using EG cells

derived from fetal material and ES cells derived from

embryos remaining after infertility treatments. In the

future, adequate scientific evidence and increased

prospect for medical benefits may be available to generate

public support for using human ES cells derived from

embryos produced through IVF for research purposes or

by SCNT for autologous transplant. We note, however,

that a responsible federal science policy does not necessarily require public funding for access to all sources of

ES or EG cells at once. At this time, therefore, the

Commission believes that federal funding for the use

and derivation of ES and EG cells should be limited

to two sources of such material: cadaveric fetal tissue

and embryos remaining after infertility treatments.

Specific recommendations and their justifications are

provided below.

Recommendation 1: 

Research involving the derivation and use of

human EG cells from cadaveric fetal tissue should

continue to be eligible for federal funding.

Relevant statutes and regulations should be

amended to make clear that the ethical safeguards

that exist for fetal tissue transplantation also
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National Bioethics Advisory Commission

apply to the derivation and use of human EG cells

for research purposes.

Considerable agreement exists, both in the United

States and throughout the world, that the use of fetal 

tissue in therapy for those with serious disorders, such as

Parkinson’s disease, is acceptable.1 Research that uses

cadaveric tissue from aborted fetuses is analogous to the

use of fetal tissue in transplantation. The rationales for

conducting EG research are equally strong, and the arguments against it are not persuasive. The removal of fetal

germ cells does not occasion the destruction of a live

fetus, nor is fetal tissue intentionally or purposefully 

created for human stem cell research. Although abortion

itself doubtless will remain a contentious issue in our

society, the procedures that have been developed to prevent fetal tissue donation for therapeutic transplantation

from influencing the abortion decision offer a model for

creating such separation in research to derive human EG

cells. Because the existing statutes are written in terms of

tissue transplantation, which is not a current feature of

EG cell research, changes are needed to make explicit

that the relevant safeguards will apply to research to

derive EG cells from aborted fetuses. 

Due to the contentious and polarizing nature of the

abortion debate in the United States, restrictions were

enacted over a decade ago to block the use of federal

funding of fetal tissue transplantation therapy research.

Until 1993, the only permissible source of tissue for such

research was tissue from spontaneously aborted fetuses

or ectopic pregnancies—sources that were largely unsuitable for research. In 1993, President Clinton lifted the

ban on the use of fetal tissue from elective abortions for

fetal tissue transplantation research. 

Previous moral opposition to fetal tissue transplant

research, because of its association with abortion, helped

shape a system of safeguards to prevent the encouragement of the practice. These rules require that the consent

process for women making abortion decisions must

precede separately from the consent process for donation

of fetal tissue for transplant research. Although some

disagree, sufficient consensus exists that society should

respect the autonomous choices of women who have

chosen to have legal abortions to donate fetal tissue for

research. If women have a right to choose to have an

abortion, it follows that the self-determination or

autonomy expressed in that right extends to the choice 

to donate fetal tissue for research purposes.

Research using fetal tissue obtained after legal elective

abortions will greatly benefit biomedical science and also

will provide enormous therapeutic benefits to those

suffering from various diseases and other conditions. In

our view, there is no overriding reason for society to

discourage or prohibit this research and thus forgo an

important opportunity to benefit science and those who

are suffering from illness and disease—especially in light

of the legality of elective abortions that provide access to

fetal tissue and of the risks involved in losing these

valuable opportunities. Indeed, the consequences of forgoing the benefits of the use of fetal tissue may well be

harmful. Moreover, if not used in research, this tissue will

be discarded.

The Acceptability of Federal Support for

Research Using Embryos Remaining After

Infertility Treatments to Derive ES Cells

The current congressional ban on embryo research

prohibits federal support of any research “in which a

human embryo...[is] destroyed, discarded, or knowingly

subjected to risk of injury greater than that allowed for

research on fetuses in utero.” 2 The term human embryo in

the statute is defined as “any organism, that is derived by

fertilization, parthenogenesis, cloning, or any other means

from one or more human gametes or human diploid cells.” 

The ban, which concerns only federally sponsored

research, reflects a moral stance either that embryos

deserve some measure of protection from society because

of their moral status as persons, or that sufficient public

controversy exists such that federal funds should not be

used for this type of research. However, some effects of

the embryo research ban raise serious moral and public

policy concerns for those who hold differing views of the

ethics of embryo research. In our view, the ban conflicts

with several of the ethical goals of medicine, especially

healing, prevention, and research—goals that are rightly

characterized by the principles of beneficence and nonmaleficence, jointly encouraging the pursuit of each

social benefit and avoiding or ameliorating potential harm.

In the United States, moral disputes—especially those

concerning certain practices in the area of human reproduction—are sometimes resolved by denying federal
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Chapter 5: Conclusions and Recommendations

funding for those practices (e.g., elective abortion), while

not interfering with the practice in the private sector. In

this case, investigative embryo research guided only by

self-regulation is a widespread practice in the private

sector, and the ban on embryo research has served to

discourage the development of a coherent public policy,

not only regarding embryo research but also regarding

health research more generally. The ban also may have

more profound effects on other areas of federally supported research that are dedicated to the relief of human

suffering, raising concerns about the distribution and

allocation of federal research resources. For example, by

limiting the federal government’s ability to fund promising

areas of basic research, a complete ban on embryo

research could prevent promising, collaborative studies

in other areas, such as cancer and genetics. We recognize

that many factors affect how federal research priorities

are set in this country. However, in our view, the intentional withholding of federal funds for research that may

lead to promising treatments may be considered unjust

or unfair.

Although no consensus has been reached regarding

the moral status of the embryo, there is agreement that if

embryo research is permissible, some limitations and/or

regulations are necessary and appropriate. Such regulation

reflects an appreciation of the disparate views regarding

the acceptability and unacceptability of this area of

scientific investigation and serves as a way of providing

accountability, allaying public anxiety, promoting

beneficial research, and demonstrating respect for human

embryos. 

Recommendation 2: 

Research involving the derivation and use of

human ES cells from embryos remaining after

infertility treatments should be eligible for federal

funding. An exception should be made to the present statutory ban on federal funding of embryo

research to permit federal agencies to fund

research involving the derivation of human ES

cells from this source under appropriate regulations that include public oversight and review.

(See Recommendations 5 through 9.)

Based on advice from the Department of Health and

Human Services (DHHS) General Counsel, the Director

of the National Institutes of Health (NIH) announced in

January 1999 that NIH will apply the ban only to

research involving the derivation of ES cells from human

embryos but not to research involving only the use of ES

cells. NIH has indicated that research proposals that

involve the use of ES cells will be considered for funding

once NIH has established a set of special guidelines that

are currently under development. The DHHS General

Counsel concluded that ES cells are not, in themselves,

organisms and hence cannot be embryos as defined by

the statute. Thus, it could be surmised from this interpretation that the only activity that could amount to

“research in which a human embryo or embryos are

destroyed” would be an attempt to derive ES cells from

living embryos. This, in fact, is the interpretation adopted

by DHHS and NIH. More than 70 members of Congress

have protested this interpretation, claiming that whatever

the language of the statute, Congress clearly intended to

prohibit not just research in which human embryos are

destroyed but also research that depends on the prior

destruction of a human embryo. Yet the plain meaning of

the statutory wording differs from this interpretation, and

nothing in its legislative history indicates that either proponents or opponents of the rider anticipated a situation

in which research that destroyed the embryo would be

conducted separately from research that used the cells

derived from the embryo. Thus, in legal terms, the

General Counsel’s interpretation appears to be reasonable, even though it does not address any of the ethical

concerns involved.

Although some may view the derivation and use of ES

cells as ethically distinct activities, we believe that it is

ethically acceptable for the federal government to finance

research that both derives cell lines from embryos

remaining after infertility treatments and that uses those

cell lines. Although one might argue that some important

research could proceed in the absence of federal funding

for research that derives stem cells from embryos remaining after infertility treatments (i.e., federally funded

scientists merely using cells derived with private funds),

we believe that it is important that federal funding be

made available for protocols that also derive such cells.

Relying on cell lines that might be derived exclusively

by a subset of privately funded researchers who are
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National Bioethics Advisory Commission

interested in this area could severely limit scientific and

clinical progress.

An ethical problem is presented in trying to separate

research in which human ES cells are used from the

process of deriving those cells, because doing so diminishes the scientific value of the activities receiving federal

support. This division—under which neither biomedical

researchers at NIH nor scientists at universities and other

research institutions who rely on federal support could

participate in some aspects of this research—rests on the

mistaken notion that derivation and use can be neatly

separated without affecting the expansion of scientific

knowledge. We believe that this misrepresentation of 

the new field of human stem cell research has several

implications.

First, researchers using human ES cell lines will

derive substantial scientific benefits from a detailed

understanding of the process of ES cell derivation,

because the properties of ES cells and the methods for

sustaining the cell lines may differ depending upon the

conditions and methods used to derive them. Thus,

scientists who conduct basic research and who are interested in fundamental cellular processes are likely to make

elemental discoveries about the nature of ES cells as they

derive them in the laboratory. Second, significant basic

research must be conducted regarding the process of ES

cell derivation before cell-based therapies can be fully

realized, and this work must be pursued in a wide

variety of settings, including those exclusively devoted to

basic academic research. Third, ES cells are not indefinitely stable in culture. As these cells are grown, irreversible changes occur in their genetic makeup. Thus,

especially in the first few years of human ES cell research,

it is important to be able to repeatedly derive ES cells in

order to ensure that the properties of the cells that are

being studied have not changed.

Thus, anyone who believes that federal support of

this important new field of research should maximize its

scientific and clinical value within a system of appropriate

ethical oversight should be dissatisfied with a position

that allows federal agencies to fund research using

human ES cells but not research through which the cells

are derived from embryos. Instead, recognizing the close

connection in practical terms between the derivation and

the use of these cells, it would be preferable to enact

provisions that apply to funding by all federal agencies,

provisions that would carve out a narrow exception for

funding of research to use or to derive human ES cells

from embryos that would otherwise be discarded by

infertility treatment programs.

The Ethical Acceptability of Creating 

Embryos Through IVF Specifically as a 

Source of ES Cells

ES cells can be obtained from human research

embryos created from donor gametes through IVF for the

sole purpose of deriving such cells for research. The primary objection to creating embryos specifically for

research is that many believe that there is a morally relevant difference between producing an embryo for the

sole purpose of creating a child and producing an

embryo with no such goal. Those who object to creating

embryos for research often appeal to arguments that

speak to respecting human dignity by avoiding the

instrumental use of human embryos (i.e., using embryos

merely as a means to some other goal does not treat them

with appropriate respect or concern as a form of human

life). Currently, we believe that cadaveric fetal tissue and

embryos remaining after infertility treatments provide an

adequate supply of research resources for federal research

projects involving human embryos. Therefore, embryos

created specifically for research purposes are not needed

at the current time in order to conduct important

research in this area.

Recommendation 3: 

Federal agencies should not fund research

involving the derivation or use of human ES cells

from embryos made solely for research purposes

using IVF.

In 1994, the NIH Human Embryo Research Panel

argued in support of federal funding of the creation of

embryos for research purposes in exceptional cases, such

as the need to create banks of cell lines with different

genetic make-ups that encoded various transplantation

antigens—the better to respond, for example, to the

transplant needs of groups with different genetic profiles.

Such a project would require the recruitment of embryos

from genetically diverse donors.
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Chapter 5: Conclusions and Recommendations

A number of points are worth considering in determining how to deal with this issue. First, it is possible

that the creation of research embryos will provide the

only opportunity to conduct certain kinds of research—

such as research into the process of human fertilization.

Second, as IVF techniques improve, it is possible that the

supply of embryos for research from this source will

dwindle. Nevertheless, we have concluded that, either

from a scientific or a clinical perspective, there is no

compelling reason to provide federal funds for the

creation of embryos for research at this time.

The Use of SCNT to Obtain ES Cells

The use of SCNT to transfer the nucleus of an adult

somatic cell into an enucleated human egg likely has the

potential of creating a human embryo. To date, although

little is known about these embryos as potential sources

of human ES cells, there is significant reason to believe

that their use may have therapeutic potential. For example,

the possible use of matched tissue for autologous cellreplacement therapy from ES cells may require the use of

SCNT. Arguably, the use of this technique to create an

embryo is different from the other cases we have considered—because of the asexual origin of the source of the

ES cells—although oocyte donation is necessarily

involved. We conclude that at this time, because other

sources are likely to provide the cells needed for the

preliminary stages of research, federal funding should

not be provided to derive ES cells from SCNT.

Nevertheless, the medical utility and scientific progress of

this line of research should be monitored closely.

Recommendation 4: 

Federal agencies should not fund research involving the derivation or use of human ES cells from

embryos made using SCNT into oocytes.

Requirements for the Donation of Cadaveric

Fetal Tissue and Embryos for Research 

Potential donors of embryos for ES cell research must

be able to make voluntary and informed choices about

whether and how to dispose of their embryos. Because of

concerns about coercion and exploitation of potential

donors, as well as controversy regarding the moral status

of embryos, it is important, whenever possible, to separate donors’ decisions to dispose of their embryos from

their decisions to donate them for research. Potential

donors should be asked to provide embryos for research

only if they have decided to have those embryos 

discarded instead of donating them to another couple 

or storing them. If the decision to discard the embryos

precedes the decision to donate them for research 

purposes, then the research determines only how their

destruction occurs, not whether it occurs.

Recommendation 5: 

Prospective donors of embryos remaining after

infertility treatments should receive timely, relevant, and appropriate information to make

informed and voluntary choices regarding disposition of the embryos. Prior to considering the

potential research use of the embryos, a prospective donor should have been presented with the

option of storing the embryos, donating them to

another woman, or discarding them. If a prospective donor chooses to discard embryos remaining

after infertility treatment, the option of donating

to research may then be presented. (At any point,

the prospective donors’ questions—including

inquiries about possible research use of any

embryos remaining after infertility treatment—

should be answered truthfully, with all information that is relevant to the questions presented.) 

During the presentation about potential research

use of embryos that would otherwise be discarded,

the person seeking the donation should

a) disclose that the ES cell research is not intended

to provide medical benefit to embryo donors,

b) make clear that consenting or refusing to donate

embryos to research will not affect the quality of

any future care provided to prospective donors,

c) describe the general area of the research to be

carried out with the embryos and the specific

research protocol, if known,

d) disclose the source of funding and expected

commercial benefits of the research with the

embryos, if known,

e) make clear that embryos used in research will

not be transferred to any woman’s uterus, and

f) make clear that the research will involve the

destruction of the embryos.

This proposal also stresses the separation that 

existing laws and policies seek between the pregnant
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National Bioethics Advisory Commission

woman’s decision to abort and her decision to donate

cadaveric fetal tissue for transplantation research.

Recommendation 1 proposes to extend that separation to

the donation of cadaveric fetal tissue for stem cell

research. It may be difficult to achieve this separation in

making decisions about embryos that remain after infertility treatments, in part because potential donors at the

outset of treatment may have chosen to donate them to

research. But, however difficult it may be to achieve, this

separation will reduce the chance that potential donors

could be pressured or coerced into donating their

embryos for stem cell research.

The parts of this recommendation that deal with providing information to donors are designed to ensure that

potential donors understand the range of available

options and that their decisions are not influenced by

anticipated personal medical benefits or by concerns

about the quality of subsequent care; that they understand that the research will involve the destruction of 

the embryos; and that they understand the nature of the

proposed research, its source of funding, and its anticipated commercial benefits, if known. Several additional

suggested information items are proposed in a document

entitled “Points to Consider in Evaluating Basic Research

Involving Human Embryonic Stem Cells and Embryonic

Germ Cells,” presented in Appendix F.

Although the ethical considerations that support the

prohibition of the designated donation of human fetal

tissue are less acute for EG cell research than they are

for transplantation, cause for concern remains. Potential

donors of cadaveric fetal tissue for EG cell derivation

would not have a direct therapeutic incentive to create or

abort tissue for research purposes, as might occur in a

transplant context. However, we agree that the prohibition remains a prudent and appropriate way to assure

that no incentive—however remote—is introduced into

a woman’s decision to have an abortion. Any suggestion

of personal benefit to the donor or to an individual

known to the donor would be untenable and potentially

coercive. Thus, the potential donor should be informed

both before and after the decision to donate that there 

is no obligation to make such a gift, that no personal

benefit will accrue as a result of the decision to donate,

and that no penalty or sanction will result from a decision

to refuse to donate.

Recommendation 6: 

In federally funded research involving embryos

remaining after infertility treatments, researchers

may not promise donors that ES cells derived from

their embryos will be used to treat patient-subjects

specified by the donors.

Current provisions regulating fetal tissue research (42

USC § 289g-1 and g-2) have been narrowly interpreted

by NIH and DHHS to apply only where fetal cellular

material is intended for transfer into a living human

recipient for therapeutic or clinical purposes. No comparable rules exist for human embryos. We believe that this

statute should be applied more broadly to include any

research involving human fetal or embryonic tissue,

regardless of its immediate or eventual therapeutic benefit or intended method of intervention. Advances in EG

cell research have demonstrated that bioethical concerns

are not limited to fetal tissue transplantation.

As noted in Chapter 3, the Uniform Anatomical Gift

Act (UAGA), currently enacted in some form in all 50

states and the District of Columbia, also may require clarification. Current versions of the UAGA explicitly permit

donors to make an anatomical gift of the human body or

body parts. Because a fetus is included within the UAGA’s

definition of decedent, either directly or by implication

depending upon the statutory language enacted, the

statute’s anatomical gift provision undermines any federal

prohibition of designated donation of human fetal tissue.

What would otherwise qualify for federal statutory 

preemption is clouded by provisions of the NIH

Revitalization Act of 1993 and the federal Common Rule,

which direct that fetal tissue transplant researchers must

abide by local and state laws, including (by implication)

the UAGA.

Finally, if and when sufficient scientific evidence

becomes available, clinical benefits are clearly anticipated,

and agreement is reached among the various elements in

society that the creation of embryos specifically for

research or therapeutic purposes is justified (specifically

through the use of SCNT), prohibitions on directed

donation should be revisited. For obvious reasons, the

use of SCNT to develop ES cells for autologous transplantation might require that the recipient be specified.
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Chapter 5: Conclusions and Recommendations

Prohibitions Against the Sale 

of Embryonic and Fetal Material

Existing rules prohibit the practice of designated

donation, the provision of monetary inducements to

women undergoing abortion, and the purchase or sale of

fetal tissue. We concur in these restrictions and in the

recommendation of the 1988 Human Fetal Tissue

Transplantation Research Panel that the sale of fetal tissue

for research purposes should not be permitted under any

circumstances. The potential for coercion is greatest

when financial incentives are present, and the treatment

of the developing human embryo or fetus as an entity

deserving of respect may be greatly undermined by the

introduction of any commercial motive into the donation

or solicitation of fetal or embryonic tissue for research

purposes.

Recommendation 7: 

Embryos and cadaveric fetal tissue should not be

bought or sold.

Policies already in place state that no for-profit trade

in fetal tissue should be permitted, and some recommend

that the “prohibition on commercial exchange of fetuses

and fetal tissue extend to tissues imported from other

countries” (Canadian Royal Commission 1993). This prohibition is intended to prevent the exploitation of poor

women—especially those in developing countries—who

might be persuaded to begin and end pregnancies for

money. An important distinction must be made between

the possible exploitation of persons that occurs when

they are coerced or inappropriately induced to sell parts

of their bodies and the exchanges that occur when companies, research institutions, or other groups provide

reasonable compensation. This is a familiar issue in discussions about remuneration for participation in research

and about which federal regulations defer to Institutional

Review Boards (IRBs) for their judgment.

Current regulations (42 USC §§ 289g-2(a), 289g2(b)(3), 274e, and 42 CFR § 46.206(b)) attempt to codify

this recommendation. Further, depending upon whether

a state has enacted the most recent revision of the UAGA

(and not all states have enacted the UAGA restriction)

and has included the fetus within its definition of

decedent, the sale of fetal remains may or may not be

prohibited by individual state statutes. Many states appear

to rely on federal statutes and regulations to prohibit fetal

tissue sale, and none address human embryos, except by

implication.

We strongly encourage those who will draft modified

legislation to frame their language in clear terms that are

specifically defined. In particular, terms such as valuable

consideration, processing, and reasonable payments require

precise definitions.

We believe that, with respect to these regulations,

different categories of research intermediaries should be

treated differently. One approach would be to establish

three intermediary categories: 1) entities responsible for

tissue harvest or embryo collection, 2) entities responsible

for stem cell derivation or other preresearch preparation

and postderivation investigators; and 3) de minimis intermediaries (including courier or supply services, off-site

specimen evaluation, pathological or chemical analysis

for research suitability, and other insignificant non- or

preresearch patient or specimen interactions). We believe

that the first category warrants the greatest degree of

regulation. An abortion provider, IVF clinic, or other

third party responsible for obtaining consent and/or collecting biological materials should not be able to commercially solicit, pay for, or be paid for the fetal or embryonic

material it obtains (permitting only a specifically defined,

cost-based reimbursement exception for entities in that

category). By placing such prohibitions against paying

those who obtain the embryos, it is our intention to

discourage the creation of excess embryos during routine

infertility procedures, which would later be used for

research purposes. 

The National Organ Transplant Act (NOTA) prohibition on tissue sale (42 USC § 274e(a)) has been criticized

for a statutory construction that focuses exclusively on

the sale of human organs. Although we agree that fetal

organ sale (as well as the sale of embryonic material)

should be prohibited, we believe that NOTA’s terms are

unacceptably narrow and that pre-organ tissues characteristic of early fetal and embryonic development should

be included in the tissue sale prohibition.

The Need for National Oversight and Review

The need for national oversight and review of ES and

EG cell research is crucial. At present, no such system
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National Bioethics Advisory Commission

exists in the United States. A national mechanism to

review protocols for deriving human ES and EG cells and

to monitor research using such cells would ensure strict

adherence to guidelines and standards across the country.

Thus, federal oversight can provide the public with the

assurance that research involving stem cells is being

undertaken appropriately. Given the ethical issues

involved in ES and EG cell research—an area in which

heightened sensitivity about the very research itself led

the President to request that the Commission study the

issue—the public and the Congress must be assured that

oversight can be accomplished efficiently, constructively,

in a timely fashion, and with sufficient attention to the

relevant ethical considerations.

Several countries, such as the United Kingdom, have

recommended the establishment of regulatory boards or

national commissions to license and regulate assisted

reproductive treatments and embryo research. The use of

a national oversight mechanism of this kind has certain

advantages, particularly because the use of law to regulate

(rather than to set limits) in this area would be burdensome, given the rapid development of biomedical science

and technology. On the other hand, some kind of national

commission or authority could provide the necessary

flexibility and adaptability, and, in addition, such an entity

could ensure more consistent ongoing application of

safeguards as well as greater public accountability. 3

In 1994, the NIH Human Embryo Research Panel

considered and then explicitly rejected reconstituting the

Ethics Advisory Board (EAB) for the purpose of reviewing

proposals involving embryos or fertilized eggs: 

Although revisiting the EAB experience offers the

potential for public consensus development and a

consistent application of the new guidelines, it

nonetheless has significant disadvantages. These

include the creation of an additional standing government board, the likelihood of significant delay before

embryo research could be funded in order to meet

legal requirements for new rulemaking prior to the

official creation of the government body, and possible

further delay if all proposals for embryo research were

required to be considered individually by an EABtype board, despite appearing to be consistent with a

developed consensus at NIH about acceptability for

funding (1994, 72).

Instead, the NIH panel recommended that 

national review of all protocols by a diverse group of

experts is warranted for a time. It is the hope of the

Panel that this ad hoc group will develop additional

guidance gained from experience with actual protocols

that can be communicated to IRBs through existing

mechanisms at NIH (1994, 73).

These recommendations envisioned a time when, following sufficient experience by the ad hoc panel, guidelines for embryo research review could be decentralized

to the local IRBs. (It was recommended that the ad hoc

panel function for at least three years.) We used similar

reasoning in a previous report when recommending that

the Secretary of Health and Human Services convene a

Special Standing Panel to review certain categories of

research involving persons with mental disorders (NBAC

1998). Like the NIH panel, we did not specify when such

guidelines could be decentralized; but unlike the NIH

panel, we did recommend that the panel be a standing

rather than an ad hoc body.

The NIH panel’s recommendations must be viewed in

the context of its reporting relationship: the panel was

charged with advising the NIH Director about research

that could be sponsored or conducted by that agency. We

note that NIH is not the only federal agency that might

be interested in sponsoring or conducting research

involving human stem cells; thus, some accommodation

must be made for the review of proposals that are not

funded by NIH. 

Other elements of the NIH panel’s recommendation

also require additional assessment. For example, the

panel recommended that “all such research proposals

continue to be specially monitored by the councils and

the NIH Office for Protection from Research Risks

[OPRR]” (1994, 74). We are less sanguine than the NIH

panel about the ability of OPRR to provide the needed

oversight and monitoring for ES and EG cell research at

this time, particularly given the recent decision to move

this office from NIH to DHHS. Although OPRR’s role in

the oversight of human subjects research, like that of the

FDA, remains central to the structure of human subjects

protections in this country, we believe that at this time,

an additional mechanism is needed for the review and

oversight of federally sponsored research involving

human ES and EG cells.
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Chapter 5: Conclusions and Recommendations

We do, however, share the concern of the 1994 NIH

panel, investigators, and IRBs that the process of protocol

review should not be viewed as simply a bureaucratic

hurdle that researchers must successfully leap solely to

satisfy a procedural or regulatory requirement. Done

well, protocol review often improves the quality of studies

by identifying concerns in the areas of study design,

selection of subjects, recruitment, informed consent, and

dissemination of results.

Recommendation 8: 

DHHS should establish a National Stem Cell

Oversight and Review Panel to ensure that all 

federally funded research involving the derivation

and/or use of human ES or EG cells is conducted

in conformance with the ethical principles and

recommendations contained in this report. The

panel should have a broad, multidisciplinary

membership, including members of the general

public, and should

a) review protocols for the derivation of ES and

EG cells and approve those that meet the

requirements described in this report,

b) certify ES and EG cells lines that result from

approved protocols,

c) maintain a public registry of approved protocols

and certified ES and EG cell lines,

d) establish a database—linked to the public 

registry—consisting of information submitted

by federal research sponsors (and, on a voluntary basis, by private sponsors, whose proprietary information shall be appropriately

protected) that includes all protocols that

derive or use ES or EG cells (including any

available data on research outcomes, including

published papers),

e) use the database and other appropriate sources

to track the history and ultimate use of certified cell lines as an aid to policy assessment

and formulation,

f) establish requirements for and provide guidance to sponsoring agencies on the social and

ethical issues that should be considered in the

review of research protocols that derive or use

ES or EG cells, and

g) report at least annually to the DHHS Secretary

with an assessment of the current state of the

science for both the derivation and use of

human ES and EG cells, a review of recent

developments in the broad category of stem

cell research, a summary of any emerging 

ethical or social concerns associated with this

research, and an analysis of the adequacy and

continued appropriateness of the recommendations contained in this report.

We recommend several functions that the panel

should carry out. In order to accomplish its purposes, the

panel should maintain a public registry of federally funded protocols that employ or derive human ES and EG

cells and, to the degree possible, a comprehensive listing

of privately funded protocols. The purpose of the registry

is to make it possible to track not only the protocols

themselves and their adherence to the principles

described above, but also their outcomes and the outcomes of all research based on their results. The panel

should be able to describe the history and trajectory of

research that uses these cells and to guard against the

promiscuous use of the cells. As they are submitted, new

federally funded protocols involving the derivation of ES

cells must include a statement that only certified cell lines

will be used.

Knowledge about the history and ultimate outcome

and use of research using human ES and EG cells should

be open to the public. Thus, the information accumulated

by the panel through the registry should be used not only

for ethical review, but also for public education. This is

an important educational and informational function 

that may encourage the active participation of the private

sector in the registry—even in the absence of any federal

regulatory requirement to do so. In addition, within five

years, the panel and the registry should be independently reviewed. This review, which should include an

evaluation of the processes of the oversight and review

mechanisms, will help to determine whether the level 

of limitations on this area of research is appropriate as

well as to determine whether case-by-case review of 

derivation protocols is still warranted.

There are several benefits to a national review process

for all federally funded research on ES and EG cells.

These include preventing ethically problematic research,
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National Bioethics Advisory Commission

assuring the public that the research is scientifically

meritorious and ethically acceptable; providing information by which to evaluate issues of social justice in the

use of the knowledge or other products of the research;

providing public oversight of controversial research practices; assuring consistency in the review of protocols;

evaluating this type of research; and educating the public. 

Although we are aware that NIH will likely conduct

and/or fund the majority of federally sponsored stem cell

research in the country and will be developing its own set

of guidelines for the conduct of ES and EG cell research,

we are persuaded that it is important to distance to some

degree the review and oversight of stem cell research from

what is the principal source of funding in this country. 

The proximity of NIH within DHHS (our recommended

location for the panel) makes it possible for a number of

beneficial arrangements to develop. These include developing requirements for data sharing as a condition for

receiving grants; developing guidelines for sharing cell

lines; and providing a common review mechanism for

other federal agencies that are conducting/funding

research involving ES and EG cells (e.g., through a

Memorandum of Understanding).

The Need for Local Review 

of Derivation Protocols

For more than two decades, prospective review by an

IRB has been the principal method for assuring that 

federally sponsored research involving human subjects

will be conducted in compliance with guidelines, policies,

and regulations designed to protect human beings from

harm. This system of local review has been subject to

criticism, and, indeed, in previous analyses we have

identified a number of concerns regarding this system of

review. In preparing this report, we considered a number

of proposals that would allow for the local review of

research protocols involving human ES and EG cell

research, bearing in mind that a decision by the

Commission to recommend a role for IRBs might be

incorrectly interpreted as endorsing the view that human

ES or EG cells or human embryos are human subjects.

We adopted the principle, reflected in these recommendations, that for research involving the derivation of

ES and EG cells, a system of national oversight and

review would be needed to ensure that important federal

sponsorship of stem cell research could proceed—but

only under specific conditions. We recognized that for

such research proposals, many of the ethical issues could

be considered at the local level—that is, at the institutions where the research would be conducted. In general,

the IRB is an appropriate body for reviewing protocols

that aim to derive ES or EG cells. Although few review

bodies (including IRBs) have extensive experience in the

review of such protocols, IRBs remain the most visible

and expert entities available. It is for this reason, for

example, that a number of recommendations presented

in this report (8, 9, 10, 11, and 12) discuss the importance of developing additional guidance for the review of

protocols that involve human stem cell research.

Recommendation 9: 

Protocols involving the derivation of human ES

and EG cells should be reviewed and approved by

an IRB or by another appropriately constituted

and convened institutional review body prior to

consideration by the National Stem Cell Oversight

and Review Panel. (See Recommendation 8.) This

review should ensure compliance with any

requirements established by the panel, including

confirming that individuals or organizations (in

the United States or abroad) that supply embryos

or cadaveric fetal tissue have obtained them in

accordance with the requirements established by

the panel.

As noted earlier, for research proposals that involve

the derivation of human ES or EG cells, particular ethical

issues require attention through a national review

process. However, this process should begin at the local

level, because institutions that intend to conduct research

involving the derivation of human ES cells or EG cells

should continue to take responsibility for ensuring the

ethical conduct of that research. More important, however,

IRBs can play an important role—particularly by reviewing

consent documents and by assuring that collaborative

research undertaken by investigators at foreign institutions has satisfied any regulatory requirements for the

sharing of research materials.

We noted in Chapter 3 that currently there is no

definitive answer to the question of whether the
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Chapter 5: Conclusions and Recommendations

Common Rule, 45 CFR 46, and/or Subpart B apply to

research involving fetal tissue transplantation, to human

embryo research, and by extension to EG and ES cell

research. If the regulations do apply, then IRBs would be

expected to review protocols, consistent with the regulatory requirements. We have indicated, however, that

even if these regulations do not apply, we believe that

IRBs should be expected to review derivation protocols to

assess their ethical acceptability without having to commit to a position that the activities are human subjects

research as defined by the regulations. If, as a matter 

of public policy, ES and EG cell research were found to

be human subjects research, certain clarifying changes 

in the regulations might be needed. For example,

Subpart B would need to provide clearly that any living

donor of human biological material constitutes a human

subject for purposes of research protection, and IRB

review and informed consent under all subparts of the

DHHS version of the Common Rule would need to apply.

Similarly, we have made clear that the authorization a

woman may give to donate fetal tissue following an elective abortion may better be understood as consent to

donate—analogous to donating organs—rather than as

providing informed consent for research participation.

Even if these models differ, the principle we adopt

remains the same: opportunity for consent should rest

exclusively with the individual or individuals legally

empowered to assume a donative role.4

Responsibilities of Federal Research Agencies

We have recommended that protocols involving the

derivation of ES or EG cells should be reviewed by both a

local review group and the national panel described in

Recommendation 8. For protocols that involve only the

use but not the derivation of ES or EG cells, oversight

and review are still necessary, but these protocols do not

require reliance on such a system. In our judgment, these

protocols can be appropriately reviewed using the

existing system for the submission, review, and approval

of research proposals that is in place at federal research

agencies, which includes the use of a peer review

group—sometimes called a study section or initial review

group—that is established to assess the scientific merit of

the proposals. In addition, in some agencies, such as

NIH, staff members review protocols before they are

transmitted to a national advisory council for final

approval. These levels of review all provide an opportunity to consider ethical issues that arise in the proposals.

When research proposals involve human subjects, in order

to assure that it is ethically acceptable, federal agencies

rely on local IRBs for review and approval. (See

Recommendation 9.) At every point in this continuum—

from the first discussions that a prospective applicant

may have with program staff within a particular institute

to the final decision by the relevant national advisory

council—ethical and scientific issues can be addressed 

by the sponsoring agency. But even if—based on a particular interpretation of the federal regulation—these

research proposals do not involve human subjects, we

believe the system of oversight and review can adequately

address the relevant ethical issues. 

Recommendation 10:

All federal agencies should ensure that their

review processes for protocols using human ES or

EG cells comply with any requirements established by the National Stem Cell Oversight and

Review Panel (see Recommendation 8), paying

particular attention to the adequacy of the justification for using such cell lines.

Research involving human ES and EG cells raises 

critical ethical issues, particularly when the proposals

involve the derivation of ES cells from embryos that

remain after infertility treatments. We recognize that

these research proposals may not follow the paradigm

that is usually associated with human subjects research.

Nevertheless, research proposals that are being considered for funding by federal agencies must, in our view,

meet the highest standards of scientific merit and ethical

acceptability. To that end, the recommendations made in

this report, including a proposed set of points to consider

in evaluating basic research involving human ES cells and

EG cells (see Appendix F), constitute a set of ethical and

policy considerations that should be reflected in the

respective policies of federal agencies conducting or

sponsoring human ES or EG cell research. 

Attention to Issues for the Private Sector

Although this report primarily addresses the ethical

issues associated with the use of federal funds for

research involving the derivation and/or use of ES and
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National Bioethics Advisory Commission

EG cells, we recognize that considerable work in both of

these areas will be conducted under private sponsorship.

Thus, our recommendations may have implications for

those working in the private sector. First, for cell lines to

be eligible for use in federally funded research, they 

must be certified by the National Stem Cell Oversight

and Review Panel described in Recommendation 8.

Therefore, if a private company aims to make its cell lines

available to publicly funded researchers, it must submit

its derivation protocol(s) to the same oversight and

review process recommended for the public sector, (i.e.,

local review; see Recommendation 9) and for certification

by the proposed national panel that the cells have

been derived from embryos remaining after infertility

treatments or from cadaveric fetal tissue.

Second, we hope that nonproprietary aspects of protocols developed under private sponsorship will be made

available in the public registry, as described in

Recommendation 8. The greater the participation of the

private sector in providing information on human ES and

EG cell research, the more comprehensive the development of the science and related public policies in this area.

Third, and perhaps most relevant in an ethically 

sensitive area of emerging biomedical research, it is

important that all members of the research community,

whether in the public or private sector, conduct the

research in a manner that is open to appropriate public

scrutiny. During the last two decades, we have witnessed

an unprecedented level of cooperation between the public

and private sectors in biomedical research, which has

resulted in the international leadership position of the

United States in this area. Public bodies and other

authorities, such as the Recombinant DNA Advisory

Committee, have played a crucial role in enabling important medical advances in fields such as gene therapy by

providing oversight of both publicly and privately funded

research efforts. We believe that voluntary participation

by the private sector in the review and certification procedures of the proposed national panel, as well as in its

deliberations, can contribute equally to the socially

responsible development of ES and EG cell technologies

and accelerate their translation into biomedically important therapies that will benefit patients.

Recommendation 11:

For privately funded research projects that involve

ES or EG cells that would be eligible for federal

funding, private sponsors and researchers are

encouraged to adopt voluntarily the applicable

recommendations of this report. This includes

submitting protocols for the derivation of ES or

EG cells to the National Stem Cell Oversight and

Review Panel for review and cell line certification.

(See Recommendations 8 and 9.)

In this report, we recommend that federally funded

research that involves the derivation of ES cells should be

limited to those efforts that use embryos that remain after

infertility treatments. Some of the recommendations

made in this context—such as the requirement for separating the decision by a woman to cease infertility treatment when embryos still remain from her decision to

donate those embryos to research—simply do not apply

to efforts to derive ES cells from embryos created

(whether by IVF or by SCNT) solely for research 

purposes—activities that might be pursued in the private

sector. Nevertheless, other ethical standards and safeguards embodied in the recommendations, such as provisions to prevent the coercion of women and the

promotion of commerce in human reproduction, remain

vitally important, even when embryos are created solely

for research purposes.

Recommendation 12: 

For privately funded research projects that involve

deriving ES cells from embryos created solely for

research purposes and that are therefore not eligible for federal funding (see Recommendations 3

and 4)

a) professional societies and trade associations

should develop and promulgate ethical safeguards and standards consistent with the principles underlying this report, and

b) private sponsors and researchers involved in

such research should voluntarily comply with

these safeguards and standards.

Professional societies and trade associations dedicated

to reproductive medicine and technology play a central

role in establishing policy and standards for clinical care,

research, and education. We believe that these organizations
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Chapter 5: Conclusions and Recommendations

can and should play a salutary role in ensuring that all

embryo research conducted in the United States, including that which is privately funded, conforms to the ethical principles underlying this report. Many of these

organizations already have developed policy statements,

ethics guidelines, or other directives addressing issues in

this report, and we have benefited from a careful review

of these materials. These organizations are encouraged to

review their professional standards to ensure not only

that they keep pace with the evolving science of human

ES and EG cell research, but also that their members are

knowledgeable about and in compliance with them. For

those organizations that conduct research in this area but

that lack statements or guidelines addressing the topics of

this report, we recommend strongly that they develop

such statements or guidelines. No single institution or

organization, whether in the public or the private sector,

can provide all the necessary protections and safeguards.

The Need for Ongoing Review and Assessment

No system of federal oversight and review of such a

sensitive and important area of investigation should be

established without at the same time providing an evaluation of its effectiveness, value, and ongoing need. The

pace of scientific development in human ES and EG cell

research likely will increase. Although one cannot predict

the direction of the science of human stem cell research,

in order for the American public to realize the promise of

this research and to be assured that it is being conducted

responsibly, close attention to and monitoring of all the

mechanisms established for oversight and review are

required.

Recommendation 13: 

The National Stem Cell Oversight and Review

Panel described in Recommendation 8 should be

chartered for a fixed period of time, not to exceed

five years. Prior to the expiration of this period,

DHHS should commission an independent evaluation of the panel’s activities to determine whether

it has adequately fulfilled its functions and

whether it should be continued.

There are several reasons for allowing the national

panel to function for a fixed period of time and for evaluating its activities before it continues its work. First,

some of the hoped-for results will be available from

research projects that are using the two sources we consider to be ethically acceptable for federal funding. Five

years is a reasonable period in which to allow some of this

information to amass, offering the panel, researchers, members of Congress, and the public sufficient time to determine whether any of the knowledge or potential health

benefits are being realized. The growing body of information in the public registry and database described above

(particularly if privately funded researchers and sponsors

voluntarily participate) will aid these considerations.

Second, within this period the panel may be able to

determine whether additional sources of ES cells are 

necessary in order for important research to continue.

Two arguments have been offered for supporting research

using embryos created specifically for research purposes:

One is the concern that not enough embryos remain for

this purpose from infertility treatments, and the other is

the recognition that some research requires embryos that

are generated for specific research and/or medical purposes. The panel should assess whether additional

sources of ES cells that we have judged to be ineligible for

federal funding at this time (i.e., embryos created solely

for research purposes) are legitimately needed.

Third, an opportunity to assess the relationship

between local review of protocols using human ES and EG

cells and the panel’s review of protocols for the derivation

of ES cells will be offered. It will, of course, take time for

this national oversight and review mechanism to develop

experience with the processes of review, certification, and

approval described in this report.

Fourth, we hope that the panel will contribute to the

broad and ongoing national dialogue on the ethical issues

regarding research involving human embryos. A recurring

theme of our deliberations, and in the testimony we

heard, was the importance of encouraging this national

conversation.

The criteria for determining whether the panel has

adequately fulfilled its functions should be set forth by an

independent body established by DHHS. However, it

would be reasonable to expect that the evaluation would

rely generally on the seven functions described above in

Recommendation 8 and that this evaluation would be

conducted by a group with the requisite expertise. In
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National Bioethics Advisory Commission

addition, some of the following questions might be considered when conducting this evaluation: Is there reason

to believe that the private sector is voluntarily submitting

descriptions of protocols involving the derivation of

human ES cells to the panel for review? Is the panel

reviewing projects in a timely manner? Do researchers

find that the review process is substantively helpful? Is

the public being provided with the assurance that social

and ethical issues are being considered?

Summary

Recent developments in human ES and EG cell research

have raised the prospect that new therapies will become

available that will serve to relieve human suffering. These

developments also have served to remind society of the

deep moral concerns that are related to research involving human embryos and cadaveric fetal tissue. Serious

ethical discussion will (and should) continue on these

issues. However, in light of public testimony, expert

advice, and published writings, we have found substantial agreement among individuals with diverse perspectives that although the human embryo and fetus deserve

respect as forms of human life, the scientific and clinical

benefits of stem cell research should not be foregone. We

were persuaded that carrying out human ES cell research

under federal sponsorship is important, but only if it is

conducted in an ethically responsible manner. After

extensive deliberation, the Commission believes that

acceptable public policy can be forged, in part, based

upon these widely shared views. Through this report, we

not only offer recommendations regarding federal funding and oversight of stem cell research, but also hope to

further stimulate the important public debate about 

the profound ethical issues regarding this potentially

beneficial research.

Notes

1 Use of fetal tissue in research is also permitted in Canada, the

United Kingdom, Australia, and in most countries in the European

Union. Germany, for example, does not permit embryo research

but does permit the use of fetal tissue for the derivation of EG

cells. The German statement concerning human ES cells upholds

the ban on destructive embryo research, effectively banning the

derivation of ES cells, because the option of deriving EG cells

exists in that country. See the German statement concerning the

question of human ES cells, March 1999, 8–10 (DFG 1999).

2 Public Law No. 105-78, 513(a) (1997).

3 EGE Opinion (1998) at Art. 2.11. See also the Australian NHMRC

Guidelines (1996) advocating that complementary national assisted

reproductive technology standards or legislation be adopted in the

Australian States.

4 See Fed. Reg. 27804, proposed rule 45 CFR § 46.204(d)-(e) and

Table 1, “Current and Proposed 45 CFR 46, Subpart B,” 27798,

explanatory text (“consent of the father is not required”; rather,

“consent of the mother or her legally authorized representative is

required” [after she is]...“informed of the reasonably foreseeable

impact of the research on the fetus”).

References

Canadian Royal Commission on New Reproductive Technologies.

1993. Proceed with Care: Final Report of the Royal Commission on

New Reproductive Technologies. 2 vols. Ottawa: Minister of

Government Services. 

Deutsche Forschungsgemeinschaf (DFG). 1999. “Statement

Concerning the Question of Human Embryonic Stem Cells,”

www.dfg-bonn.de/english/press/eszell_e.html. 

European Commission. European Group on Ethics (EGE). 1998.

“Opinion of the European Group on Ethics in Science and New

Technologies.” 

National Bioethics Advisory Commission (NBAC). 1998. 

Research Involving Persons with Mental Disorders That May Affect

Decisiomaking Capacity. 2 vols. Rockville, MD: U.S. Government

Printing Office.

National Health and Medical Research Council (NHMRC). 1996.

Draft Statement on Ethical Guidelines on Assisted Reproductive Technology.

Canberra, Australia: Australian Government Publishing Service.

National Institutes of Health (NIH). Human Embryo Research

Panel. 1994. Report of the Human Embryo Research Panel. 2 vols.

Bethesda, MD: NIH.

This report benefited from the input of many individuals and groups. Several organizations responded to

a February 1999 request from the National Bioethics

Advisory Commission for input on the scientific, medical, and ethical issues involved in human stem cell

research, and nearly 40 scientific, medical, professional,

religious, and health organizations were asked to provide

their perspectives on these complex issues. The

Commission gratefully acknowledges the thoughtful

comments provided by the following groups:

■ American Bioethics Advisory Commission 

(Stafford, Virginia)

■ The American College of Obstetricians and

Gynecologists (Washington, DC)

■ The American Society for Cell Biology 

(Bethesda, Maryland)

■ American Society for Reproductive Medicine

(Birmingham, Alabama)

■ Association of American Medical Colleges

(Washington, DC)

■ Biotechnology Industry Association 

(Washington, DC)

■ College of American Pathologists 

(Northfield, Illinois)

■ Pharmaceutical Research and Manufacturers 

of America (Washington, DC)

■ RESOLVE (Somerville, Massachusetts)

I

n addition, the Commission asked the following 

individuals to review portions of the draft report for

scientific, legal, and ethical accuracy. The comments

provided by these individuals improved the quality and

outcome of the report and are greatly appreciated:

■ Brigid L.M. Hogan (Vanderbilt University School of

Medicine; Nashville, Tennessee)

■ Anna Mastroianni (University of Washington;

Seattle, Washington)

■ John A. Robertson (The University of Texas; 

Austin, Texas)

■ Janet Rossant (Samuel Lunenfeld Research Institute,

Mt. Sinai Hospital; Toronto, Ontario)

■ Lee Silver (Princeton University; Princeton, 

New Jersey)

■ Evan Y. Snyder (Harvard Medical School;

Cambridge, Massachusetts)

■ James A. Thomson (University of Wisconsin;

Madison, Wisconsin)

We are also grateful to Michelle Myer, a graduate

student at the University of Virginia, for preparing a

summary of the presentations that were provided to the

Commission on May 7, 1999, on religious perspectives

relating to research involving human stem cells. The

summary appears as Appendix E of this report.

83

Acknowledgments

Appendix A

adult stem (AS) cells – stem cells found in the adult

organism (e.g., in bone marrow, skin, and intestine) that

replenish tissues in which cells often have limited life

spans. They are more differentiated than embryonic stem

(ES) cells or embryonic germ (EG) cells.

ART (assisted reproductive technology) – all treatments

or procedures that involve the handling of human eggs

and sperm for the purpose of helping a woman become

pregnant. Types of ART include in vitro fertilization,

gamete intrafallopian transfer, zygote intrafallopian transfer, embryo cryopreservation, egg or embryo donation,

and surrogate birth.

blastocyst – a mammalian embryo in the stage of development that follows the morula. It consists of an outer

layer of trophoblast to which is attached an inner cell

mass.

blastomere – one of the cells into which the egg divides

after its fertilization; one of the cells resulting from the

division of a fertilized ovum.

chimera – an organism composed of two genetically

distinct types of cells.

cloning – the production of a precise genetic copy of a

molecule (including DNA), cell, tissue, plant, or animal.

differentiation – the specialization of characteristics or

functions of cell types.

diploid cell – the cell containing two complete sets of

genes derived from the father and the mother respectively;

the normal chromosome complement of somatic cells (in

humans, 46 chromosomes).

ectoderm – the outer layer of cells in the embryo; the

origin of skin, the pituitary gland, mammary glands, and

all parts of the nervous system.

embryo – 1) the beginning of any organism in the early

stages of development, 2) a stage (between the ovum and

the fetus) in the prenatal development of a mammal, 

3) in humans, the stage of development between the second and eighth weeks following fertilization, inclusive.

embryonic stem (ES) cells – cells that are derived from

the inner cell mass of a blastocyst embryo.

embryonic germ (EG) cells – cells that are derived from

precursors of germ cells from a fetus.

endoderm – the innermost of the three primary layers of

the embryo; the origin of the digestive tract, the liver, the

pancreas, and the lining of the lungs.

ex utero – outside of the uterus.

fibroblast – a cell present in connective tissue, capable of

forming collagen fibers.

gamete – 1) any germ cell, whether ovum or spermatozoon, 2) a mature male or female reproductive cell.

gastrulation – the process of transformation of the

blastula into the gastrula, at which point the embryonic

germ layers or structures begin to be laid out.

germ cells – gametes (ova and sperm) or the cells that

give rise directly to gametes.

haploid cell – a cell with half the number of chromosomes

as the somatic diploid cell, such as the ova or sperm. In

humans, the haploid cell contains 23 chromosomes. 

85

Glossary

Appendix B
86

Appendix B: Glossary

in vivo – in the natural environment (i.e., within the body).

in vitro – in an artificial environment, such as a test tube

or culture medium.

in vitro fertilization (IVF) – a process by which a

woman’s eggs are extracted and fertilized in the laboratory and then transferred after they reach the embryonic

stage into the woman’s uterus through the cervix.

Roughly 70 percent of assisted reproduction attempts

involve IVF, using fresh embryos developed from a

woman’s own eggs.

karyotype – the chromosome characteristics of an

individual cell or of a cell line, usually presented as a

systematic array of metaphase chromosomes from a

photograph of a single cell nucleus arranged in pairs in

descending order of size.

mesoderm – the middle of the three primary germ layers of the embryo; the origin of all connective tissues, all

body musculature, blood, cardiovascular and lymphatic

systems, most of the urogenital system, and the lining of

the pericardial, pleural, and peritoneal cavities.

morula – 1) the mass of blastomeres resulting from the

early cleavage divisions of the zygote, 2) solid mass of

cells resembling a mulberry, resulting from the cleavage

of an ovum.

oocyte – 1) a diploid cell that will undergo meiosis (a

type of cell division of germ cells) to form an egg, 2) an

immature ovum.

ovum – female reproductive or germ cell.

pluripotent cells – cells, present in the early stages of

embryo development, that can generate all of the cell

types in a fetus and in the adult and that are capable of

self-renewal. Pluripotent cells are not capable of developing into an entire organism. 

pre-implantation embryo – 1) the embryo before it has

implanted in the uterus, 2) commonly used to refer to 

in vitro fertilized embryos before they are transferred to a

woman’s uterus.

somatic cells – [from soma - the body] 1) cells of the

body which in mammals and flowering plants normally

are made up of two sets of chromosomes, one derived

from each parent, 2) all cells of an organism with the

exception of germ cells.

stem cells – cells that have the ability to divide indefinitely and to give rise to specialized cells as well as to new

stem cells with identical potential.

totipotent – having unlimited capacity. Totipotent cells

have the capacity to differentiate into the embryo and

into extra-embryonic membranes and tissues. Totipotent

cells contribute to every cell type of the adult organism. 

trophoblast – the outermost layer of the developing blastocyst of a mammal. It differentiates into two layers, the

cytotrophoblast and syntrophoblast, the latter coming

into intimate relationship with the uterine endometrium

with which it establishes nutrient relationships.

zygote – 1) the cell resulting from the fusion of two

gametes in sexual reproduction, 2) a fertilized egg

(ovum), 3) the diploid cell resulting from the union of a

sperm and an ovum, 4) the developing organism during

the first week after fertilization.
87

Letters of 

Request and Response

Appendix C





An Overview of Food and Drug

Administration Regulations Pertinent to

Human Cellular Materials and Tissues

The Food and Drug Administration (FDA) has had in

place a regulatory framework for cellular and tissue

materials that has evolved over time as the development

and use of such biological materials for therapeutic purposes has increased. The Public Health Service Act (PHS

Act), 42 USC 262 and 264, the Federal Food, Drug, and

Cosmetic Act (FD&C Act), 21 USC 201 et seq., and

implementing regulations of the FDA provide the agency

with broad authority to regulate both the research into

and the use of human stem cells that are intended to be

used as biological products, drugs, or medical devices in

order to prevent, treat, cure, or diagnose a disease or condition.2 Scientific research not intended for use in the

development of any FDA-regulated product is not under

the oversight and control of the FDA.

In order for the FDA to assert its regulatory authority

over stem cell-related research and products, such

research and products must fall within one of the product categories over which the FDA exercises jurisdiction

and must move in interstate commerce. To the extent that

the FDA determines that a particular product falls within

the definition of a biological product, a drug, or a medical device, it will assert its jurisdiction. Whether a particular product falls within the definition of any of the

FDA-regulated product categories will depend, in part,

upon the intended use of the product. 

The manufacturer’s objective intent—as evidenced by

labeling, promotional, and other relevant materials for

the product—has long been regarded as the primary

source for establishing a product’s intended use and thus

its status for purposes of FDA regulation.3 Although this

approach would seem to grant manufacturers unlimited

control over the regulatory status of their products,

courts in fact have recognized the FDA’s right to look

beyond the express claims of manufacturers in order to

consider more subjective indicia of intent—such as the

foreseeable and actual use of a product—to prove that its

intended use subjects it to agency jurisdiction.4

Regardless of whether the FDA or the manufacturer 

is characterizing the intended use of a product for purposes of evaluating FDA jurisdiction, it is clear that FDA

regulatory authority will not extend automatically to all

scientific research on stem cells. Indeed, to the extent

that such nonhuman research is preliminary in nature

and/or is undertaken without intent to develop a therapeutic product, stem cell research is not subject to FDA

jurisdiction. Thus, for example, basic research to develop

stem cell models to evaluate the safety and efficacy of

therapeutic products would not be regulated directly.

Instead, the FDA would review any scientific data generated from such a model and submitted as part of a marketing application. It is only at the juncture when the

science of stem cell research has progressed to the point

that development of a particular therapeutic product and

its use in humans is envisioned that FDA regulatory

authority will apply, and further research then must be

conducted in compliance with FDA requirements.

Even if a product falls within one of the defined categories over which the FDA asserts its jurisdiction, no

93

The Food and Drug

Administration’s Statutory 

and Regulatory Authority to

Regulate Human Stem Cells1

Appendix D
94

Appendix D: The Food and Drug Administration’s Statutory and Regulatory Authority to Regulate Human Stem Cells 

statutory authority over the product exists unless it moves

in interstate commerce. The FDA takes an expansive view

of what constitutes interstate commerce; in regard to biological products, the FDA has been particularly aggressive. For example, in its 1993 policy statement regarding

somatic cell therapy products, the FDA concluded that

[t]he interstate commerce nexus needed to require

premarket approval under the statutory provisions

governing biological products and drugs may be created in various ways in addition to shipment of the

finished product by the manufacturer. For example,

even if a biological drug product is manufactured

entirely with materials that have not crossed State

lines, transport of the product into another State by

an individual patient creates the interstate commerce

nexus. If a component used in the manufacture of the

product moves interstate, the interstate commerce

prerequisite for the prohibition against drug misbranding is also satisfied even when the finished

product stays within the State. Products that do not

carry labeling approved in a PLA (or NDA) are misbranded under section 502(f)(1) of the [FD&C]

Act....Moreover, falsely labeling a biological product

is prohibited under section 351(b) of the PHS Act

without regard to any interstate commerce nexus (42

U.S.C. 262(b)) (58 Fed. Reg. at 53250). 

It can be expected that the FDA would apply the same

logic to all cellular and tissue materials that are used in

the prevention, treatment, cure, or diagnosis of a disease

or condition.

Application to Stem Cells

In recent congressional testimony, National Institutes

of Health Director Harold Varmus described three potential applications of research using human “pluripotent

stem cells” that illustrate the inconsistencies of FDA regulation. He noted that the FDA does not regulate two of

the examples, but will regulate one. First, stem cell

research could include basic research such as “the identification of the factors involved in the cellular decisionmaking process that determines cell specialization.”5

Second, “[h]uman 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 process.”6 It is unlikely that the FDA

would regulate either of these potential applications

directly. Varmus also made the following comments:

Perhaps the most far-reaching potential application of

human pluripotent stem cells is the generation of cells

and tissue that could be used for transplantation, socalled cell therapies. Pluripotent stem cells stimulated

to develop into specialized cells offer the possibility of

a renewable source of replacement cells and tissue to

treat a myriad of diseases, conditions and disabilities

including Parkinson’s and Alzheimer’s disease, spinal

cord injury, stroke, burn, heart disease, diabetes,

osteoarthritis and rheumatoid arthritis.7

These stem cell products, based on their intended use,

would be subject to FDA regulation.

Case-by-Case Regulation

The FDA has been cautious in exercising its regulatory

discretion regarding cellular and tissue materials and in

fact never has overseen a single regulatory program for

human cellular and tissue-based products. Instead, the

FDA has regulated these products on a case-by-case

basis, responding as it deemed appropriate to the particular characteristics of and concerns raised by each type of

product.8

One example has been the FDA’s approach to regulating bone marrow. Although for years the FDA has

licensed blood and blood components pursuant to section 351 of the PHS Act (42 USC 262), it voluntarily has

refrained from regulating minimally manipulated bone

marrow, the earliest source of stem cells used for transplantation, despite its status as a blood component.

Indeed, not until the early 1990s did the FDA announce

that to the extent that bone marrow was subject to extensive manipulation prior to transplantation, it would be

treated the same as somatic cell therapy and gene therapy

products subject to the investigational new drug (IND)

regulations and would require PHS Act licensure (58 Fed.

Reg. 53248, 53249 (Oct. 14, 1993)). 

Also in 1993, in response to concerns regarding the

transmission of the human immunodeficiency virus

(HIV) and other infectious diseases, the FDA published an
95

National Bioethics Advisory Commission

emergency final rule that mandated certain processing,

testing, and recordkeeping procedures for specific types

of tissue products.9 This rule, however, did not mandate

premarket approval or notification for all tissues, but

rather provided, among other things, for donor screening, documentation of testing, and FDA inspection of

tissue facilities.10

Another example of the FDA’s case-by-case approach

is the publication in 1996 of a guidance that stated that

manipulated autologous structural cells (autologous

cells manipulated and then returned to the body for

structural repair or reconstruction) would be subject to

PHS licensure.11 In addition, until recently, the FDA

carefully chose not to regulate reproductive tissues.

Then, in 1997, it proposed that, in the future, certain

reproductive tissues (i.e., semen, ova, and embryos)

should be regulated in some form.

Traditional tissue products (including but not limited

to bone, skin, corneas, and tendons) also have been subject to the FDA’s piecemeal regulatory approach.

Historically, the FDA regulated these products on an ad

hoc basis as medical devices under section 201 of the

FD&C Act. However, with the advent of HIV and the

potential for its transmission, the FDA concluded in the

early 1990s that a more comprehensive program for 

regulating the use of traditional tissues was necessary. In

1991, the FDA concluded that human heart valves were

medical devices subject to premarket approval requirements.12 Following litigation, the FDA decided that while

these products were indeed medical devices, they would

not be subject to premarket approval requirements.13 In

defining tissue subject to this rule, the FDA exempted

a number of products, including vascularized organs,

dura mater, allografts, and umbilical cord vein grafts.

A New Approach to Regulating Human

Cellular and Tissue-Based Products

In February 1997 the FDA proposed a new approach to the

regulation of human cellular and tissue-based products.

This framework is intended to “protect the public health

without imposing unnecessary government oversight”

(“Reinventing the Regulation of Human Tissue,” National

Performance Review, February 1997). Although it is still

considered a proposed approach, the 1997 document

utilizes FDA’s existing statutory authority under the

PHS and FD&C Acts to regulate a broad array of cellular and tissue materials. The framework proposed is a

tiered approach to regulation (FDA, “A Proposed

Approach to the Regulation of Cellular and TissueBased Products,” February 28, 1997). Products that

pose increased risks to health or safety would be subject to increased levels of regulation (i.e., either licensure under the PHS Act or premarket approval under

the FD&C Act), while products that pose little or no

risk of transmitting infectious disease would be subject

to minimal regulation (e.g., facility registration and

product listing). However, products that are 1) highly

processed (more-than-minimally manipulated); 2) are

used for other than their usual purpose; 3) are combined

with nontissue components (e.g., devices or other therapeutic products); or 4) are used for metabolic purposes

(e.g., systemic, therapeutic purposes) will be subject to

clinical investigation as INDs, must be documented with

investigational device exemption applications (IDEs),

and will be subject to premarket approval as biological

products, medical devices, or new drugs.

This proposed approach addresses the FDA’s regulation of stem cell products. In the case of a minimally

manipulated product for autologous use and allogeneic

use of cord blood stem cells by a close blood relative, the

FDA has proposed requiring compliance with standards

consistent with section 361 of the PHS Act, rather than

an IND and licensure pursuant to section 351 of the act.

However, minimally manipulated products that will be

used by an unrelated party will be regulated under section 351 of the Act. The FDA also intends to develop

standards—including disease screening requirements,

establishment controls, processing controls, and product

standards: “If sufficient data are not available to develop

processing and product standards after a specified period

of time, the stem cell products would be subject to IND

and marketing application requirements.”14 Stem cell

products that are more-than-minimally manipulated will

require INDs and licensing under section 351 of the PHS

Act. For example, stem cell products that are to be used

for a nonhomologous function or are more-than-minimally manipulated will be required to be licensed under
96

Appendix D: The Food and Drug Administration’s Statutory and Regulatory Authority to Regulate Human Stem Cells 

section 351. The FDA also has articulated “increased

safety and effectiveness concerns for cellular and tissuebased products that are used for nonhomologous function, because there is less basis on which to predict the

product’s behavior.”15

Implementation of the Proposed Approach

The FDA has begun to implement the proposed

approach with the publication on January 20, 1998,

of a Request for Proposed Standards for Unrelated

Allogeneic Peripheral and Placental/Umbilical Cord Blood

Hematopoietic Stem/Progenitor Cell Products” (63 Fed.

Reg. 2985 ), utilizing its standards-setting authority under

section 361 of the PHS Act.16 In this notice, the FDA

requests product standards to ensure the safety and

effectiveness of stem cell products, which should be

supported by clinical and nonclinical laboratory data.

The FDA also announced its intention to phase in over a

three-year period implementation of IND application and

license application requirements for minimally manipulated unrelated allogeneic hematopoietic stem/progenitor

cell products. The notice states that “[i]f adequate information can be developed, the agency intends to issue

guidance for establishment controls, processing controls,

and product standards....FDA intends to propose that, in

lieu of individual applications containing clinical data,

licensure may be granted for products certified as meeting issued standards.” If, however, the FDA determines

that adequate standards cannot be developed, the agency

has expressed its intention to enforce IND and licensing

requirements at the end of three years. Proposals are due

on or before January 20, 2000.

On May 14, 1998, the FDA proposed Establishment

Registration and Listing for Manufacturers of Human

Cellular and Tissue-Based Products (63 Fed. Reg. 26744).

The agency describes the proposed registration and listing requirements as a first step towards accomplishing its

goal of putting into place a comprehensive new system of

regulation for human cellular and tissue-based products.

Registration and listing is intended to allow the FDA to

assess the state of the cell and tissue industry, “to accrue

basic knowledge about the industry that is necessary for

its effective regulation,” and to facilitate communication

between the agency and industry (Ibid. at 26746). As

proposed, the registration and listing requirements

would apply to human cellular and tissue-based products

that the FDA will regulate under section 361 of the PHS

Act.17 Among the products designated for regulation

under that section and consequently subject to registration and listing are bone, tendons, skin, corneas, as well

as peripheral and cord blood stem cells under certain

conditions, and sperm, oocytes, and embryos for reproductive use (Ibid. at 26746).

FDA Discretion Entitled 

to Great Deference

Today there is a vast array of biological products that

have been approved by the FDA and many others that are

awaiting FDA action.18 These products are scientifically

complex and rarely lend themselves to categorization. As

a result, the FDA invariably is required to determine on

a case-by-case basis whether its existing statutory

authority applies to a new product, which particular

authority to apply, and, if so, what evidence will adequately demonstrate proof of safety, purity, and potency

(efficacy). The decision of whether and how to regulate a

product is made based upon the FDA’s expert determination and upon the particular facts and circumstances,

the historical application of the law to similar products,

the applicable statutory and regulatory criteria, and the

state of the FDA’s scientific understanding at the time of

the approval.

The FDA’s exercise of the significant discretion provided to the agency by Congress is entitled to great deference by the courts.19 In a recent challenge to the FDA’s

approval of a biological product under the PHS Act, the

District Court for the District of Columbia held that

“FDA’s policies and its interpretation of its own regulations will be paid special deference because of the breadth

of the Congress’ delegation of authority to FDA and because

of FDA’s scientific expertise.”20

Moreover, even if the FDA has not asserted jurisdiction previously with regard to reproductive tissue, for

example, it is within the agency’s statutory authority

that its policies are evolutionary. The Supreme Court

has recognized that expert administrative agency interpretations are not “carved in stone. On the contrary, the
97

National Bioethics Advisory Commission

agency...must consider varying interpretations and the

wisdom of its policy on a continuing basis” (emphasis

added).21 Furthermore, the Court has acknowledged that

“regulatory agencies do not establish rules of conduct to

last forever....[A]n agency must be given ample latitude

to ‘adapt their rules and policies to the demands of

changing circumstances.’”22

Conclusion

The FDA has developed a comprehensive approach to

the regulation of cellular and tissue-based therapeutic

products under its jurisdiction, including human stem

cells. Nonclinical and clinical stem cell research undertaken to develop a therapeutic product intended to treat

human disease will continue to be regulated by the FDA,

while basic scientific research and other nonhuman

research will remain outside of the agency’s purview.

Notes

1 The content of this appendix is based upon a paper commissioned

by the National Bioethics Advisory Commission and prepared by

Brady, R.P., M.S. Newberry, and V.W. Girard, “The Food and Drug

Administration’s Statutory and Regulatory Authority to Regulate

Human Pluripotent Stem Cells,” available in Volume II of this report.

2 The scope of this appendix is limited to human stem cells. The

FDA has a similar regulatory structure to regulate animal stem cell

products used as animal drugs (21 USC 360b). The U.S. Department

of Agriculture has the authority to regulate animal stem cell products

used in animal vaccines (21 USC 151).

3 See United States v. An Article...Sudden Change, 409 F.2d 734, 

739 (2d Cir. 1969). 

4 See National Nutritional Foods Ass’n. v. Mathews, 557 F.2d. 325,

334 (2d Cir. 1977); Action on Smoking and Health v. Harris, 

655 F.2d 236, 240–41 (D.C. Cir. 1980).

5 Statement of Harold Varmus, M.D., Director, National Institutes

of Health, before the Senate Appropriations Subcommittee on

Labor, Health and Human Services, Education and Related

Agencies. December 2, 1998. Meeting transcript, 3.

6 Ibid.

7 Ibid. 3–4.

8 63 Fed. Reg. 26744 (May 14, 1998) (FDA Proposed Rule

“Establishment and Listing for Manufacturers of Human Cellular

and Tissue-Based Products”).

9 “Human Tissue Intended for Transplantation” 58 Fed. Reg. 65514

(Dec. 14, 1993).

10 In 1997, FDA finalized its 1993 emergency rule establishing

processing, testing, and recordkeeping requirements for all tissue

products. “Human Tissue Intended for Transplantation” 62 Fed.

Reg. 40429 (July 29, 1997). 

11 CBER, Guidance on Applications for Products Comprised of

Living Autologous Cells Manipulated Ex Vivo and Intended for

Structural Repair or Reconstruction (May 1996).

12 “Cardiovascular Devices; Effective Date of Requirement for

Premarket Approval; Replacement Heart Valve Allograft” 56 Fed.

Reg. 29177 (June 26, 1991).

13 FDA Rescission Notice, 59 Fed. Reg. 52078 (October 14, 1994).

14 Proposed Approach, 25.

15 Proposed Approach, 16.

16 While FDA may choose to implement this policy through 

regulation, FDA also may implement it on a case-by-case basis. 

See infra, Section VI.

17 Consistent with the discussion supra, Section III. A., the preamble

to the proposed rule states that “use of human cellular or tissuebased products solely for nonclinical scientific or educational 

purposes does not trigger the registration or listing requirements.

Any use for implantation, transplantation, infusion, or transfer into

humans is considered clinical use and would be subject to part

1271 [the registration and listing requirements]” Ibid. 26748.

18 Today, biological products are available or under development to

treat, diagnose, or prevent virtually every serious or life-threatening

disease. Available products include, but are not limited to, vaccines

(manufactured both in traditional ways and through the use of

biotechnology); human blood and blood-derived products; monoclonal or polyclonal immunoglobulin products; human cellular 

(i.e., gene therapy) products; protein, peptide, and carbohydrate

products; protein products produced in animal body fluids by

genetic alteration of the animal (i.e., transgenic animals); animal

venoms; and allergenic products.

19 U.S. v. Rutherford, 442 U.S. 544, 553 (1979); Bristol-Myers

Squibb Co. v. Shalala, 923 F. Supp. 212, 216 (D.D.C. 1996).

20 Berlex Laboratories, Inc. v. FDA et al., 942 F. Supp. 19 

(D.D.C. 1996) (emphasis added). See also Lyng v. Payne, 

476 U.S. 926 (1986).

21 Chevron, U.S.A., Inc. v. Natural Resources Defense Council, Inc.,

467 U.S. 837, 863–64 (1984).

22 Motor Vehicle Mfrs. Ass’n. of the U.S. v. State Farm Mut. Auto. 

Ins. Co., 463 U.S. 29, 42 (1983) (citations omitted).

Introduction

As part of the National Bioethics Advisory

Commission’s deliberations for this report, a meeting was convened on May 7, 1999, at Georgetown

University in order for the Commission to hear testimony

from prominent scholars of religious ethics on their traditions’ views of human stem cell research. Although it

would be inappropriate for religious views to determine

public policy in our country, such views are the products

of long traditions of ethical reflection, and they often

overlap with secular views. Thus, the Commission

believed that testimony from scholars of religious ethics

was crucial to its goal of informing itself about the range,

content, and rationale of various ethical positions

regarding research in this area.

The Commission heard testimony from scholars who

work within the Roman Catholic, Protestant, Eastern

Orthodox, Jewish, and Islamic faiths. Although the presenters were able to reach consensus on several significant issues related to embryonic stem (ES) and

embryonic germ (EG) cell research, disagreement

emerged among the religious traditions represented and

often within each tradition itself, particularly between

restrictive and permissive positions on several issues.

Roman Catholic Perspectives

The restrictive, “official” position within Roman

Catholicism opposes EG and ES cell research, primarily

because obtaining stem cells from either aborted fetal

tissue or embryos that remain following clinical in vitro

fertilization (IVF) procedures involves the intentional

destruction of a genetically unique, living member of the

human species. According to this view, it is impermissible to obtain stem cells from in vitro fertilized blastocysts, because doing so results in the destruction of the

blastocyst—a human life worthy of full moral protection

from the moment of conception. No amount of benefit to

others can justify the destruction of the blastocyst, an act

that would be equivalent to murder. 

Similarly, from this perspective, it is impermissible to

obtain EG cells from the gonadal tissue of aborted

fetuses, because although such harvesting is not directly

responsible for the death of the fetus, it nevertheless

involves complicity with the evil of abortion. Moreover,

to make use of any therapy derived from research on

either human embryonic or fetal tissue and to contribute

to the development or application of such research

through general taxation would involve complicity in the

destruction of human life. Federal funding, which in a

sense would make all citizens complicit in this research,

thus would greatly impose upon the consciences of

Catholics. 

However, even the restrictive position of the Roman

Catholic Church does not oppose stem cell research per

se. The central moral impediment to such research concerns the sources from which stem cells are derived. The

act of harvesting stem cells from other sources—miscarried fetuses, placental blood, or adult tissues—would not

be intrinsically immoral. In fact, this perspective, recognizing the potential benefits to human health of stem cell

research, encourages investigation into the feasibility of

99

Summary of Presentations 

on Religious Perspectives

Relating to Research Involving

Human Stem Cells, May 7, 1999

Appendix E
100

Appendix E: Summary of Presentations on Religious Perspectives Relating to Research Involving Human Stem Cells

such alternative sources. In practice, however, stem cell

research, even with alternative stem cell sources, would

remain morally problematic for two reasons. First, some

are concerned that any safeguards will be ineffective

because, in the face of potentially promising and lucrative

research, the temptation to transgress such safeguards

might be irresistible. Second, many fear that the benefits

of this research might not be distributed equitably and

are concerned that stem cell research perhaps may not be

the best use of national resources, given the preponderance of so many other unmet human needs.

Although all Roman Catholics share a variety of

important basic convictions, individual Catholics often

differ in how to interpret them in practice. According to

a less restrictive Catholic perspective, this disagreement

is due, at least in part, to a commitment to the theory of

natural law—a commitment that, while a fundamental

part of the Catholic tradition, also involves reliance upon

an “imperfect science.” A commitment to natural law

involves belief in a moral order that can be “seen” by all

human beings in the reality of creation itself. But because

the act of “looking” entails “a complex process of discernment and deliberation, and a structuring of insights,

a determination of meaning, from the fullest vantage

point available, given a particular history—one that

includes the illumination of Scripture and the accumulated wisdom of the tradition”—what any two human

beings see will not always be the same.1

With respect to stem cell research, the major areas of

disagreement among Catholics are also those upon which

the restrictive voice within Catholicism most strongly

bases its opposition: the moral status of the embryo and

the moral permissibility of using aborted fetuses as

sources of stem cells. In contrast to this restrictive view of

the embryo, another Catholic might, with the aid of science, look to the reality of the early human embryo and

see that which is not yet an “individualized human entity with the settled inherent potential to become a human

person.”2 Because the early embryo, according to this less

restrictive view, is not a person, it is sometimes permissible to use it in research, though as human life it must

always be accorded some respect. Similarly, one might

decide that adequate barriers—such as a prohibition

against the directed donation of cadaveric fetal tissue,

and the distinction between somatic cell nuclear transfer

(SCNT) for research or therapy and SCNT for reproduction—can be erected between the use of aborted fetal

tissue in research and the act of abortion itself so that

engaging in the former does not amount to complicity in

the latter. From this perspective, then, a Catholic may be

able to support ES cell research without sacrificing a

commitment to the fundamental principles that define

Catholicism, including the duties to protect human life,

honor the sacred, and promote distributive justice in

health care. Finally, because of the diversity within and

among ethical traditions, this perspective is congruent

with the restrictive Catholic view that individuals who

oppose this research should not be forced to contribute

to it but, contrary to the restrictive view, favors an

approach that would allow federal funding, but with

accommodations made to permit conscientious objection.

To summarize the testimony of the Roman Catholic

panel, all agree that in light of certain agreed-upon principles, major Catholic concerns with regard to both

embryonic and nonembryonic stem cell research include

the following issues: 1) the moral status of the early

embryo, 2) complicity with abortion in using fetal tissue

as a source of stem cells, 3) the need for safeguards, distributive justice, and just allocation of national resources,

and 4) the difficulty in federally funding research to

which many are opposed on moral and religious

grounds. The major disagreements arise from conflicting

interpretations of the broad principles, which in turn

lead to different responses to these four major concerns.

Jewish Perspectives

The two main sources of Jewish ethics—theology and

law—yield several principles relevant to a Jewish ethical

analysis of stem cell research. First, human beings are

merely the stewards of their bodies, which belong to

God. Moreover, God has placed conditions on the use of

the human body, including the command that health and

life must be preserved. Second, human beings are God’s

partners in healing, and in order to fulfill God’s command, they have a duty to use any means available to

heal themselves, whether these means are natural or

artificial. Third, because all human beings, regardless of
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ability, are created in the image of God, they are valuable.

Fourth, human beings, unlike God, lack perfect knowledge of the consequences of their actions and in the

process of trying to improve themselves or the world

must, therefore, be careful to avoid causing harm to

them.

Four potential moral impediments to EG and ES cell

research arise from these Jewish principles: 1) the moral

status of the fetus and of the act of abortion, 2) potential

complicity with evil, 3) the commandments to respect

the dead, and 4) the moral status of the embryo.

According to Conservative Judaism, the fetus until

the 40th day after conception is “like water.” Although

the fetus becomes a potential and partial person after the

40th day, and is thus entitled to a certain amount of

respect and protection, it remains primarily a part of the

pregnant woman’s body, and does not become an independent person with full moral rights until the greater

part of its body emerges from the womb during birth.

Because of the command to preserve human health and

life, if either the health or the life of the woman is clearly

threatened by the fetus, abortion is not only permissible

but obligatory, as she is a full person while the fetus

remains only a part of her and a potential person. When

the woman’s health is at some increased risk but is not

clearly compromised by the pregnancy, abortion is permissible but not obligatory. More recently, some Jewish

authorities also permit abortion in cases in which the

fetus has a terminal disease or serious malformations.

According to Orthodox Judaism, on the other hand,

after 40 days of gestation, the fetus becomes a person

with full moral rights and may not be aborted except to

protect the pregnant woman’s health. Yet, even though

abortion after 40 days is viewed by the Orthodox Jews as

homicide, it does not follow from this perspective that

life-saving use of stem cells procured from illegitimately

aborted fetuses is impermissible (although the question

of who can legitimately give consent to such procurement is problematic from this perspective). Although this

perspective recognizes the possibility that therapeutic use

of aborted fetuses may make abortion appear less heinous,

the strength of the commandment to preserve life, for

which all other laws must be suspended except those 

prohibiting murder, idolatry, and sexual transgressions,

overrides this concern. Thus, despite the disagreement

within Judaism regarding the moral status of the fetus

and the permissibility of abortion after 40 days, all agree

that neither source of stem cells is illegitimate. One

caveat to this consensus is that some within Conservative

Judaism who accept the permissibility of abortion to preserve the life or health of the woman nevertheless require

that stem cells be procured only from fetuses that have

been legitimately aborted; Orthodox Judaism, by contrast, appears to hold that although abortion after 40 days

postconception is generally impermissible, there is no

complicity involved in using these aborted fetuses as

sources of stem cells.

Jewish thinkers agree that commandments to respect

the dead, which require that corpses not be mutilated or

left unburied longer than necessary, can be suspended in

order to save lives. Because of the strong commandment

to preserve life and health, for example, Jewish law permits both autopsies and organ procurement when they

will benefit the living. Reasoning by analogy, if tissue procurement from the cadavers of full persons in order to

benefit human health and life is permitted, then tissue

procurement from dead fetuses—which according to

some Jewish perspectives are less than full persons—

must also be permitted for the same purpose provided

that (for some interpreters) the abortion itself was 

permissible according to Jewish law.

There is also wide consensus within Judaism that no

serious moral impediments exist to using IVF embryos as

sources of stem cells because extra-corporeal embryos

have no status under Jewish law. These entities lack status because all embryos prior to 40 days postconception

are “like water” and because as extra-corporeal entities,

they lack the status of potential and partial person that is

accorded to fetuses, which develop from embryos

implanted in a uterus. Although extra-corporeal embryos

merit a certain respect as human life, they are closest in

moral status to gametes and thus may be discarded,

frozen, or used as life-saving sources of stem cells. In fact,

so long as they are never implanted, there is no clear legal

prohibition against creating embryos for research purposes, although extra-legal norms may raise ethical questions about this practice.
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Appendix E: Summary of Presentations on Religious Perspectives Relating to Research Involving Human Stem Cells

Because stem cells can be permissibly procured either

from extra-corporeal embryos or from legitimately

aborted fetuses, stem cell research is not considered

intrinsically immoral. Rather, stem cell research becomes

morally problematic when applied in a variety of contexts. First, Judaism views the provision of health care as

a communal duty. Thus, a context in which the benefits

of stem cell research are not accessible to all persons who

are in need would be problematic. Similarly, it may be

problematic to focus national resources in this area of

research rather than in other areas of need. In addition,

although obtaining consent to procure stem cells is necessary, it may be challenging. Finally, there is widespread

agreement that stem cell research should not be used to

enhance human beings, although some disagreement

exists over whether it may be used to improve health or

whether it must be reserved only for life-saving purposes.

Eastern Orthodox Perspectives

According to Eastern Orthodoxy, all human beings are

created in the image of God and grow continuously

toward the likeness of God. Although the embryo, fetus,

and adult are each at different stages of this process, all

share the same potential for attaining authentic personhood, and each, with God’s grace, will attain such personhood. According to this belief, God has given us

medicine in order to heal, and any misuse of this gift that

results in the destruction of potentially authentic persons

is considered illegitimate. Thus, although miscarried

fetuses may be used as sources of EG cells, neither electively aborted fetuses nor blastocysts may be so used.

However, despite the impermissibility of procuring ES

cells from blastocysts, because cell lines from this source

already exist and have the potential to save lives, it is considered wasteful to discard these lines, and it is in fact

permissible to use them. No complicity is thought to

arise from such use. On the other hand, it is not permissible to procure EG cells from aborted fetuses, as such

procurement would involve complicity.

Even assuming that stem cells could be permissibly

procured, Eastern Orthodoxy shares with other religious

traditions a variety of concerns about the context in

which stem cell research might be applied, including

addressing the problems of equitable access to the benefits of the research and other problems that can occur

when market forces control the research; using the

research for eugenic or cosmetic purposes, rather than

for healing; and obtaining the informed, voluntary

consent of the woman or couple.

Islamic Perspectives

Islam consists of two major schools of thought—Sunni

and Shi‘i—both of which refer to the same historical

sources. Although these two schools differ somewhat in

their views of abortion, in general, Islam regards the life

of the fetus as developing over several stages, and personhood is considered a process. Although from the

moment of conception the embryo is a human life meriting some protection, it is not commonly thought to attain

personhood until it is ensouled, some time around the

fourth month of gestation. Thus, because of the enormous potential to improve human health through this

type of research, the vast majority of followers of Islam

would agree that it is permissible to use early human

embryonic life for this purpose. Moreover, it is permissible to use the tissue from illegitimately aborted fetuses to

save lives, just as it is permissible to use cadaveric organs

to save lives, even when the cadaveric organ source has

been wrongfully killed. Finally, with caution, it can be

deduced that creating embryos for research purposes is

also permissible from an Islamic perspective, as long as

those embryos are not implanted.

Protestant Perspectives

Protestant positions range dramatically from the highly

restrictive to the nonrestrictive in this area. For example,

according to restrictive Protestant view, a person is not

defined by his or her capacities; rather, a person is a

human being with a personal history, regardless of

whether he or she is aware of that history. From this perspective, embryos are simply the weakest and least

advantaged people among us. Because procuring stem

cells from embryos requires the destruction of the

embryo, such procurement thus raises serious moral

issues, despite the ease with which it might be used to
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National Bioethics Advisory Commission

attain undeniably positive consequences for others, and

rather than accepting the use of illicit means to achieve a

good end, we should search for alternative, permissible

means. Similarly, using aborted fetuses as sources of EG

cells amounts to complicity with evil, and procurement

of EG cells even from permissibly aborted fetuses (however that category is defined) would involve using a

human life twice for another’s benefit—first, to benefit

the woman who aborted and then to benefit society

through EG cell research. Therefore, from this perspective, it is impermissible to derive stem cells from

embryos, whether spare or created for this purpose, and

from aborted fetuses, whether permissibly aborted or

not. The use of alternative sources of stem cells—for

example, from bone marrow or umbilical cord blood—

would, however, be permissible.

For Protestants whose views are less restrictive on this

issue, the moral status of the embryo is more ambiguous.

Although even nascent human life—which retains the

potential for full human life—deserves respect and protection from callous disregard, the early embryo and the

late fetus are viewed in moral terms as significantly different. Because the potential benefits of ES and EG cell

research are so substantial, the moral difference between

the early embryo and the developed fetus becomes compelling in this case, and it is thus permissible to use

human life at the blastocyst stage to benefit other lives.

No embryos should be created solely for this purpose,

however, unless no other sources are available, and

attempts should be made to locate alternative sources of

stem cells that do not involve the destruction of embryos.

It is permissible to procure EG cells from aborted fetuses,

as long as safeguards are erected to prevent the therapeutic use of aborted fetal tissue from either increasing

the frequency of abortion or encouraging a callous view

of early human life. Moreover, although less restrictive

Protestant views permit the procurement of stem cells

from both proposed sources, this procurement must

occur within a context of respect for nascent human life,

only when significant benefit can be derived from it, and

only after broad public discussion and acceptance of

such research. If the general public is excluded from a

discussion of this research, then public support of this

and future beneficial research may be compromised.

Furthermore, the requirement that all members of society

have the opportunity to participate in open, sustained

dialogue about these decisions is critical from this perspective, and if federal funds are to be allocated toward

this research, conscientious objectors should be accommodated. Finally, most Protestants share previously articulated contextual concerns regarding 1) ensuring global

access to the benefits of this research, 2) avoiding the

negative consequences that might come with marketcontrolled research, and 3) assessing the priority of these

research efforts relative to other current and pending

health-related research projects.

Summary of Broad Areas of Agreement

and Disagreement 

Not surprisingly, the panelists did not reach unanimity

on all aspects of human ES and EG cell research.

Although some differences exist among the various religious traditions, these mostly concern the appropriate

sources and methods of religious-ethical reasoning. On

substantive issues, less restrictive individuals across most

religious traditions appear to have more in common with

each other than with restrictive members of their own

faiths. (The same is true for commonalities among

restrictive members of all faiths.) The substantive issues

relevant to stem cell research on which there is internal

disagreement include the following:

1) The moral status of the embryo. The perceived status of

the embryo ranges from full moral personhood with

correlative inviolable rights to life to an early, extracorporeal biological entity lacking any significant

moral status. Between these poles, although the

embryo tends to be viewed as valuable because of its

current status as a form of human life and its potential status as a person, it is ultimately, if tragically,

subordinate to the health needs of actual persons.

2) Whether the use of EG cells derived from aborted fetuses

involves complicity with the perceived evil of abortion. On

one end of the spectrum is the view that many abortions are permissible. Thus, complicity with evil is

either never or rarely a consideration. On the other

end of the spectrum is the view that all deliberate

abortions are immoral, and that any use of EG cells

derived from aborted fetuses involves complicity.
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Appendix E: Summary of Presentations on Religious Perspectives Relating to Research Involving Human Stem Cells

Those who take more moderate positions argue that

even when abortion is wrong, it is not wrong to use

tissue that would otherwise be discarded, or that

complicity can be avoided by erecting barriers

between abortion and stem cell procurement, such as

a prohibition of directed donation.

3) Whether stem cell research should, ideally, be federally

funded. Some, based on their belief in the duty to heal,

hold that stem cell research should proceed as quickly

as possible (given certain conditions; see below),

while others hold that any federal funding that

enables immoral research is itself immoral and would

involve conscientious citizens in complicity against

their will. The moderate view holds that in the

absence of agreement on such issues as the moral status of the embryo, conscientious objectors should be

allowed to opt out of federal support for the research

and that without any federal support, privatized

human ES and EG cell research will make contextual

goals such as distributive justice even more difficult to

realize.

Despite these areas of disagreement, widespread consensus was reached both within and among the various

religious traditions on several important issues in ES and

EG cell research:

1) Stem cell research is not inherently immoral, and in

fact has the potential to contribute important knowledge that can lead to therapies for certain diseases,

provided that morally legitimate sources of cells are

used (although this is defined differently), and provided that important contextual factors of justice and

regulation are addressed. (See #3 below.)

2) If society chooses to embark upon federally funded

ES and EG cell research, it must do so under conditions of respect for the humanity of the embryo. It

would be preferable if there existed alternative

sources of stem cells that did not involve the direct or

indirect destruction of human life, and efforts should

be made to identify such sources.

3) In order for the research to be morally permissible,

several “background factors” must be in place,

including

■ assurance of equitable access to the benefits of the

research,

■ appropriate prioritization of this research relative

to other social needs,

■ assurance that the research will be used to treat

disease, not enhance humans,

■ public education, discussion, and acceptance of

human stem cell research, and

■ public scrutiny, oversight, and regulation of the

research.

4) Assuming that privately funded research will continue in this area, it is preferable that a public body—

even one that is funded with tax dollars—be required

by law to review all private sector research and to

make this review part of the public record, despite the

possibility that the connection between the government and ES and EG cell research may be perceived

as legitimating research that some citizens will continue to consider immoral.

Meeting Participants

Catholicism

Kevin W. Wildes, S.J., Ph.D., Georgetown University

Edmund D. Pellegrino, M.D., Georgetown University

Margaret Farley, Ph.D., Yale University

Judaism

Rabbi Elliot N. Dorff, Ph.D., University of Judaism

Rabbi Moshe Tendler, Ph.D., Yeshiva University

Laurie Zoloth, Ph.D., San Francisco State University

Eastern Orthodoxy

Father Demetrios Demopulos, Ph.D., Holy Trinity

Greek Orthodox Church

Islam

Abdulaziz Sachedina, Ph.D., University of Virginia

Protestantism

Gilbert C. Meilander, Jr., Ph.D., Valparaiso

University

Nancy J. Duff, Ph.D., Princeton University Theological

Seminary

Ronald Cole-Turner, M.Div., Ph.D., 

Pittsburgh Theological Seminary

Notes

1 Farley, M., “Roman Catholic Views on Research Involving

Human Embryonic Stem Cells.” Testimony before NBAC. 

May 7, 1999. Washington DC. Meeting transcript, 3.

2 Ibid. 5.
This document describes some of the ethical, scientific,

and legal issues that could be considered when

designing and/or reviewing studies that involve access to

and use of human stem cells. These Points to Consider are

relevant only for designing and evaluating studies in

which the role of the individual(s) who provide gametes,

cadaveric fetal tissue, or embryos is limited to providing

these materials for research intended to develop generalizable new knowledge. This document results from the

recommendations described in this report and therefore

is intended for use by those who design, conduct, and

review research involving human embryonic stem (ES)

and embryonic germ (EG) cells using federal funds.

Private researchers and sponsors also may find this document to be of use. These Points to Consider do not apply

to situations in which an individual would be the recipient of a stem cell-based therapy, nor do they apply to

studies involving human/animal hybrids.

I. Scientific and Research Design

Considerations

The ethical acceptability of any research protocol

depends, in part, on its scientific merit, the qualifications

of investigators, the protocol’s overall design characteristics, and the precise nature of the materials and operations employed. In these respects, several issues arise

when designing research involving human ES and EG

cells, consideration of which would help ensure not only

that the research is well designed, important, feasible,

and timely, but also that a number of important ethical

matters are considered. These issues are of particular significance given the nature of the materials to be used in

research. 

A. What are the sources from which human ES and 

EG cells will be obtained?

1. From existing cell lines 

2. From cadaveric fetal tissue (following elective

abortion or surgical termination of ectopic

pregnancy)

3. From embryos remaining after infertility treatments

4. From embryos created solely for research purposes1

B. Has previous and requisite research been conducted

using nonhuman animal models?

C. Are there valid alternatives to using human ES and

EG cells in the proposed research?

D. What are the future plans for conservation of

gametes, cadaveric fetal tissue, and embryos?

1. Will ES or EG cells be produced and stored for

later use?

2. If a particular protocol is being proposed that uses

embryos remaining after infertility treatments,

does it propose to use only the minimum number

of embryos necessary? 

3. What plans exist in the event that additional ES or

EG stem cells are needed?

E. In what setting will the research be conducted?

1. Are the investigators scientifically qualified to

carry out the proposed research?

2. Is the research environment (including facilities)

appropriate for the conduct of research involving

stem cells?

105

Points to Consider in Evaluating

Basic Research Involving Human

Embryonic Stem Cells and

Embryonic Germ Cells

Appendix F
106

Appendix F: Points to Consider in Evaluating Basic Research Involving Human Embryonic Stem Cells and Embryonic Germ Cells

II. Identification of Providers and

Donors and Recruitment Practices

and Compensation

Several issues should be considered when identifying

individuals (or couples) who may be asked to consider

providing gametes, fetal tissue, or embryos for research;

consideration of these issues could help to ensure that no

inappropriate burden, inducement, or exploitation

would occur.

A. Identification and recruitment practices

1. Are potential donors or providers identified

through advertisements to the general public? Are

they identified through direct solicitation? Do they

self-select?

2. Is the selection of such individuals equitable

and fair?

3. Are these individuals vulnerable to undue influence, coercion, or exploitation? Does the recruitment method raise concerns about undue

influence or coercion of the prospective donors? 

4. Are the potential donors capable of consenting?

5. In which circumstances is it appropriate to identify

and recruit an individual as well as his or her

partner?

B. Compensation and reimbursement

1. Will any financial compensation be paid to individuals (or couples) who donate materials; and if

so, will the details of this compensation be disclosed?

2. Does the compensation reimburse the individual

(or couple) solely for the additional expenses that

relate to this particular project?

3. When is the offer of compensation made relative

to an individual’s (or couple’s) decision to make

available the materials from which stem cells will

be derived?

III. Consent to Donate

Several issues arise in the process of providing information to individuals and couples who may be donating

cadaveric fetal tissue or embryos remaining after infertility treatments. Considering these issues would help to

ensure that prospective donors or providers of source

materials would receive timely, relevant, and appropriate

information to make informed and voluntary choices. In

some cases, these issues are unique to the provision of

gametes, embryos, or fetal tissue; in other cases. the items

are important in other situations as well. 

A. General considerations for individuals (or couples)

who donate cadaveric fetal tissue or embryos remaining after infertility treatments 

1. Who will seek the consent? Will a clinician and/or

researcher be available to answer questions?

2. Is it appropriate for others to participate in the

consent process (e.g., partner or family member)? 

3. Will psychological support mechanisms be in place

if needed?

4. Are the purposes of ES or EG cell research (in

general) described fully?

5. Will the consent form clearly disclose that stem

cell research is not intended to benefit the donor

directly?

6. Is it clear that decisions to consent to or refuse the

procedures to obtain stem cells will not affect the

quality of care the patient will receive?

7. Will individuals be informed that no medical or

genetic information about the fetal tissue,

embryos, or stem cells derived from these sources

will be available to any outside individual or entity?

8. What measures will be taken to protect the privacy and confidentiality of individuals who provide cadaveric fetal tissue or embryos?

9. Is the source of funding for the research (public,

private, public/private, philanthropic) disclosed?

10.What known commercial benefits, if any, are

expected to arise for the investigators seeking to

obtain human ES or EG cells?

B. Additional considerations specific to consent to

donate cadaveric fetal tissue

1. Is there a description of what usually is done with

fetal tissue at the institution at which a pregnancy

will be terminated? Is this information available in

written form and provided to individuals?

2. Is permission to conduct research immediately

available?
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National Bioethics Advisory Commission

C. Additional considerations specific to consent to

donate embryos remaining after infertility treatments 

1. Are the methods of disposal of embryos remaining

after infertility treatments described? Is this information available in written form and provided to

patients? 

2. Will information be made available about whether

the embryos were viable and normal or not? 

3. Is there a description of the options available (e.g.,

permit material to be used in research, cryopreserve, discard, or donate to another couple for

infertility treatment)?

4. Is it clear that the embryos used in research will

not, under any circumstances, be transferred to

any woman’s uterus? 

5. Is it clear that the research will result in the

destruction of the embryo? Is the method

described?

IV. Review Issues

Because of the special nature of human ES and EG cells,

several issues arise in the review and oversight of research

involving their use. The Commission has recommended

a system of national oversight and review, combined with

local monitoring. Careful and thoughtful consideration

of these issues will provide assurance that, regardless of

the source of funding, appropriate compliance with

applicable regulations, guidelines, and other standards

will occur. These considerations would supplement, not

replace, applicable federal and state regulations. 

A. Applicability of relevant regulations

1. What current guidelines, regulations, rules, or

policies apply to the conduct of this research? If

ambiguity exists, how will it be resolved?

2. What mechanisms are in place to assure compliance with these regulations?

3. What regulations apply for collaborating with

international researchers (e.g., importing fetal 

tissue or embryos from other countries)?

B. Applicability of professional practice standards

C. Submission of research findings for publication

D. Other responsibilities of investigators and collaborating clinicians

Note

1 The National Bioethics Advisory Commission has recommended

that federal agencies should not fund research involving the derivation or use of human ES cells from embryos created solely for

research purposes. (See Recommendations 3 and 4.)

January 19, 1999 (Washington, DC)

Public:

E.J. Suh, Collegians Activated to Liberate Life

Kneale Ewing, Collegians Activated to Liberate Life

Olga Fairfax

Will Goodman 

Expert:

Harold Varmus, National Institutes of Health

John Gearhart, The Johns Hopkins University 

James Thomson, University of Wisconsin 

Austin Smith, University of Edinburgh

Daniel Perry, Alliance for Aging Research

Patricia King, Georgetown University School of Law 

John Robertson, University of Texas School of Law

Erik Parens, The Hastings Center 

Françoise Baylis, Dalhousie University 

Ted Peters, Center for Theology and the Natural Sciences 

Karen Lebacqz, Pacific School of Religion

February 2–3, 1999 (Princeton, New Jersey)

Expert:

David Blumenthal, Massachusetts General Hospital

Brigid Hogan, Vanderbilt University

Barbara Mishkin, Hogan & Hartson L.L.P.

Robert Brady, Hogan & Hartson L.L.P.

March 2–3, 1999 (Vienna, Virginia)

Expert:

John Fletcher, University of Virginia 

Lori Knowles, The Hastings Center 

LeRoy Walters, Georgetown University

April 16, 1999 (Charlottesville, Virginia)

Public:

Richard Doerflinger, National Conference of Catholic Bishops

Edward Furton, National Catholic Bioethics Center

Karen Poehailos

Sidney Gunst, Jr.

Ida Chow, American Society of Cell Biology

Ethics and Religious Liberty Commission of the Southern 

Baptist Convention (submitted written testimony)

May 7, 1999 (Washington, DC)

Public:

Dena Davis, Cleveland-Marshall College of Law

Richard Doerflinger, National Conference of Catholic Bishops

Expert:

Kevin Wildes, Georgetown University

Edmund Pellegrino, Georgetown University

Margaret Farley, Yale University

Demetrios Demopulos, Holy Trinity Greek Orthodox Church 

Elliot Dorff, University of Judaism

Moshe Tendler, Yeshiva University

Laurie Zoloth, San Francisco State University

Abdulaziz Sachedina, University of Virginia

Gilbert Meilander, Jr., Valparaiso University

Nancy Duff, Princeton University Theological Seminary

May 11–12, 1999 (Northbrook, Illinois) 

Public:

Daniel McConchie, Center of Bioethics and Human Dignity

Expert:

Lori Andrews, Chicago–Kent College of Law

Sander Shapiro, University of Wisconsin–Madison

June 28, 1999 (Washington, DC)

Public:

Phil Noguchi, Food and Drug Administration

109

Public and Expert Testimony

Appendix G

State Regulation of 

Embryo Stem Cell Research

Lori B. Andrews

Chicago-Kent College of Law

The Food and Drug Administration’s 

Statutory and Regulatory Authority to 

Regulate Human Pluripotent Stem Cells 

Robert P. Brady, Molly S. Newberry, and Vicki W. Girard

Hogan & Hartson L.L.P.

Quick Response:

Use of Human Fetal Tissue 

in Federally Funded Research

Elisa Eiseman

RAND Science and Technology Policy Institute

Analysis of Federal Laws Pertaining 

to Funding of Human Pluripotent 

Stem Cell Research

Ellen J. Flannery and Gail H. Javitt

Covington & Burling

Deliberating Incrementally on Human

Pluripotential Stem Cell Research

John C. Fletcher

University of Virginia

Bioethical Regulation of Human Fetal Tissue

and Embryonic Germ Cellular Material: Legal

Survey and Analysis 

J. Kyle Kinner, Presidential Management Intern

National Bioethics Advisory Commission

Regulating Embryonic Stem Cell Research:

Biomedical Investigation of Human Embryos

J. Kyle Kinner, Presidential Management Intern

National Bioethics Advisory Commission

International Perspectives 

on Human Embryo and 

Fetal Tissue Research

Lori P. Knowles

The Hastings Center

What Has the President Asked of NBAC? 

On the Ethics and Politics of Embryonic 

Stem Cell Research

Erik Parens

The Hastings Center

Locating Convergence:

Ethics, Public Policy, and 

Human Stem Cell Research

Andrew W. Siegel

The Johns Hopkins University

111

Commissioned Papers

Appendix H

The following papers, prepared for the National Bioethics Advisory Commission, are available in Volume II of this report: